Statistical methods to adjust for the effects on intervention compliance in randomized clinical trials where precision treatment rules are being developed.

Background: Heterogeneity of treatment effects (HTEs) can occur because of either differential treatment compliance or differential treatment effectiveness. This distinction is important, as it has action implications, but it is unclear how to distinguish these two possibilities statistically in precision treatment analysis given that compliance is not observed until after randomization. We review available statistical methods and illustrate a recommended method in secondary analysis in a trial focused on HTE.

Synthesis of three-dimensional covalent organic frameworks through a symmetry reduction strategy.

Three-dimensional (3D) covalent organic frameworks (COFs) hold significant promise for a variety of applications. However, conventional design approaches using regular building blocks limit the structural diversity of 3D COFs. Here we design and synthesize two 3D COFs, designated as JUC-644 and JUC-645, through a methodology that relies on using eight-connected building blocks with reduced symmetry.

One-quarter of freshwater fauna threatened with extinction.

Freshwater ecosystems are highly biodiverse and important for livelihoods and economic development, but are under substantial stress. To date, comprehensive global assessments of extinction risk have not included any speciose groups primarily living in freshwaters. Consequently, data from predominantly terrestrial tetrapods are used to guide environmental policy and conservation prioritization, whereas recent proposals for target setting in freshwaters use abiotic factors.

Janus graphene nanoribbons with localized states on a single zigzag edge.

Topological design of π electrons in zigzag-edged graphene nanoribbons (ZGNRs) leads to a wealth of magnetic quantum phenomena and exotic quantum phases. Symmetric ZGNRs typically show antiferromagnetically coupled spin-ordered edge states. Eliminating cross-edge magnetic coupling in ZGNRs not only enables the realization of a class of ferromagnetic quantum spin chains, enabling the exploration of quantum spin physics and entanglement of multiple qubits in the one-dimensional limit, but also establishes a long-sought-after carbon-based ferromagnetic transport channel, pivotal for ultimate scaling of GNR-based quantum electronics.

Heritable polygenic editing: the next frontier in genomic medicine?

Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. Several recent books and academic papers have outlined the ethical concerns raised by germline genome editing and the opportunities that it may present. To date, no attempts have been made to predict the consequences of altering specific variants associated with polygenic diseases.

Analytical expressions of specific yield for shallow groundwater estimation and modeling.

Specific yield (S) is an essential hydrogeological parameter in groundwater-related modeling and estimation. In this study, we proposed several new analytical expressions of S to characterize the nonlinear variations of S under shallow groundwater environments, encompassing S for three-layered soil, transition zone S, and flux-dependent S (in Boussinesq-type equation). The proposed S expression for three-layered soils expanded the applicability of previous expressions for homogeneous soil.

Dynamically Stable Cu0Cuδ+ Pair Sites Based on In Situ-Exsolved Cu Nanoclusters on CaCO3 for Efficient CO2 Electroreduction.

Copper-based catalysts are the choice for producing multi-carbon products (C2+) during CO2 electroreduction (CO2RR), where the Cu0Cuδ+ pair sites are proposed to be synergistic hotspots for C-C coupling. Maintaining their dynamic stability requires precise control over electron affinity and anion vacancy formation energy, posing significant challenges. Here, we present an in-situ reconstruction strategy to create dynamically stable Cu0Cu0.

Prevalence and risk factors of myopic macular degeneration: the Aier-SERI high myopia adult cohort.

Purpose: To assess the prevalence and risk factors of myopic macular degeneration (MMD) in young and middle-aged individuals with high myopia in Changsha, central China.

Methods: A total of 445 adults with high myopia (worse than or equal to -5.0 D) were examined between 2021 and 2023.

Multitargeting Pt(IV) Derivatives of Cisplatin or Oxaliplatin Inhibit Tumor Growth in Mice without Inducing Neuropathic Pain.

Cisplatin and oxaliplatin are Pt(II) anticancer agents that are used to treat several cancers, usually in combination with other drugs. Their efficacy is diminished by dose-limiting peripheral neuropathy (PN) that affects ∼70% of patients. PN is caused by selective accumulation of the platinum drugs in the dorsal root ganglia (DRG), which overexpress transporters for cisplatin and oxaliplatin.

Coordination of Focal Adhesion Nanoarchitecture and Dynamics in Mechanosensing for Cardiomyoblast Differentiation.

Focal adhesions (FAs) are force-bearing multiprotein complexes, whose nanoscale organization and signaling are essential for cell growth and differentiation. However, the specific organization of FA components to exert spatiotemporal activation of FA proteins for force sensing and transduction remains unclear. In this study, we unveil the intricacies of FA protein nanoarchitecture and that its dynamics are coordinated by a molecular scaffold protein, BNIP-2, to initiate downstream signal transduction for cardiomyoblast differentiation.

Mortality of gastrointestinal cancers attributable to smoking, alcohol, and metabolic risk factors, and its association with socioeconomic development status 2000-2021: GI Cancer Mortality and Risk Factors.

Objective: Gastrointestinal (GI) cancers account for one-third of global cancer mortality, with nearly half being preventable. This study updates the global burden of GI cancers attributed to major risk factors: smoking, alcohol, and metabolic disturbances.

Methods: We utilized data from the Global Burden of Disease Study 2021 to examine trends in death and age-standardized death rates related to GI cancers caused by smoking, alcohol, high body mass index (BMI), and high fasting blood glucose (FBG) from 2000 to 2021.

Date seeds polysaccharides as novel capping agents for selenium nanoparticles: Synthesis, characterization, stability, biological activities, and gut microbiota modulation.

Date seed polysaccharides were utilized to synthesize selenium nanoparticles (MPS-NP) through a redox reaction involving sodium selenite and ascorbic acid. Characterization of MPS-NP showed a uniform, amorphous, spherical shape with a particle size of 89.2 nm, remaining stable for 42 days.

Leveraging Cross-Diversity Machine Learning to Unveil Metal-Organic Frameworks with Open Copper Sites for Biogas Upgrading.

Biogas, primarily composed of methane (CH) and carbon dioxide (CO), is considered an alternative renewable energy resource. Efficient CO/CH separation is essential for biogas upgrading to increase energy density, and in this context, metal-organic frameworks (MOFs) have demonstrated significant potential. Here, we integrate multiscale modeling with cross-diversity machine learning (ML) to unveil MOFs with open copper sites (OCS-MOFs) that exhibit exceptional CO/CH separation performance.

Cell-Active, Arginine-Targeting Irreversible Covalent Inhibitors for Non-Kinases and Kinases.

Targeted covalent inhibitors (TCIs) play an essential role in the fields of kinase research and drug discovery. Most existing TCIs are however cysteine- or lysine-reactive, thus severely limiting their potential applications. New types of TCIs capable of covalently targeting other nucleophilic amino acids that are readily available in proteins are urgently needed.

Modulation of CRISPR-Cas9 cleavage with an oligo-ribonucleoprotein design.

Clustered regularly interspaced short palindromic repeats (CRISPR) associated protein Cas9 system has been widely used for genome editing. However, the editing or cleavage specificity of CRISPR Cas9 remains a major concern due to the off-target effects. The existing approaches to control or modulate CRISPR Cas9 cleavage include engineering Cas9 protein and development of anti-CRISPR proteins.

Stretchable Polymer Hydrogels Based Flexible Triboelectric Nanogenerators for Self-Powered Bioelectronics.

The rapid development of flexible electronics has led to unprecedented social and economic improvements. But conventional power devices cannot adapt to the advances of flexible electronics. Triboelectric nanogenerators (TENGs) have been used as robust power sources to transform ambient mechanical energy into electricity, thus meeting the power requirements of flexible electronics.

Body Composition in Adults Born at Very Low Birthweight-A Sibling Study.

Background: Individuals born preterm at very low birthweight (VLBW, < 1500 g) tend to attain a smaller adult body size compared with term-born peers but less is known regarding specific body composition characteristics.

Objectives: We aimed to assess whether adults born at VLBW have less beneficial body composition characteristics, potentially mediating the association between VLBW birth and cardiometabolic disease. Sibling controls were used to account for the potential influence of shared genetic and/or lifestyle factors.

Comparative phenotypic and proteomic analysis of colistin-exposed .

Introduction: The emergence of colistin resistance threatens the treatment of infections.

Methods: In this study, in vitro development of colistin resistance was investigated using comparative phenotypic and proteomic analysis of ATCC 9027, its 14-day colistin sub-MIC exposed strain (Col-E1), and 10-day antibiotic-free cultured Col-E1 strain (Col-E2). Antibiotic susceptibility, morphology, virulence factors, and proteomic changes were assessed using disc-diffusion, agar-based, spectrophotometry, SEM, and iTRAQ-LC-MS/MS methods.

"If I could try it, I'd try it": Qualitative study of the illegal vaping culture in Singapore.

Aims And Background: Singapore has one the world's strictest e-cigarette (vaping) regulations, with bans on e-cigarette import, sale, purchase, use and possession. Nevertheless, Singapore is seeing a growing vaping trend. Beyond estimates of vaping prevalence, little is known about vaping in countries where it is banned or the features and drivers of such illegal vaping cultures.

Packing Engineering of Zirconium Metal-Organic Cages in Mixed Matrix Membranes for CO2/CH4 Separation.

Metal-organic cages (MOCs) have been considered as emerging zero-dimensional (0D) porous fillers to generate molecularly homogenous MOC-based membrane materials. However, the discontinuous pore connectivity and low filler concentrations limit the improvement of membrane separation performance. Herein, we propose the dimension augmentation of MOCs in membranes using three-dimensional (3D) supramolecular MOC networks as filler materials in mixed matrix membranes (MMMs).

Identification and monitoring of cell heterogeneity from plasmid recombination during limonene production.

Detecting alterations in plasmid structures is often performed using conventional molecular biology. However, these methods are laborious and time-consuming for studying the conditions inducing these mutations, which prevent real-time access to cell heterogeneity during bioproduction. In this work, we propose combining both flow cytometry and fluorescence-activated cell sorting, integrated with mechanistic modelling to study conditions that lead to plasmid recombination using a limonene-producing microbial system as a case study.

Aqueous Proteomic and Metabolomic Profiles in Low-Energy vs High-Energy Femtosecond Laser-Assisted Cataract Surgery.

Purpose: To investigate the aqueous proteomics and metabolomics in low-energy and high-energy femtosecond laser-assisted cataract surgery (FLACS).

Methods: In this prospective observational study, 72 patients were randomized to 3 groups: low-energy FLACS, high-energy FLACS, and conventional phacoemulsification (controls). Aqueous was collected after femtosecond laser treatment or at the beginning of surgery (controls).

Spatially Resolved Tumor Ecosystems and Cell States in Gastric Adenocarcinoma Progression and Evolution.

Gastric cancer (GC) is a major cause of global cancer mortality with high levels of heterogeneity. To explore geospatial interactions in tumor ecosystems, we integrated 2,138 spatial transcriptomic regions-of-interest (ROIs) with 152,423 single-cell expression profiles across 226 GC samples from 121 patients. We observed pervasive expression-based intratumor heterogeneity, recapitulating tumor progression through spatially localized and functionally ordered subgroups associated with specific immune microenvironments, checkpoint profiles, and genetic drivers such as SOX9.

EZH2 modulates mRNA splicing and exerts part of its oncogenic function through repression of splicing factors in CML.

The polycomb protein EZH2 is up-regulated in Chronic Myeloid Leukaemia (CML) and associated with transcriptional reprogramming. Here we tested whether EZH2 might also act as a modulator of the mRNA splicing landscape to elicit its oncogenic function in CML. We treated CML cell lines with EZH2 inhibitors and detected differential splicing of several hundreds of events, potentially caused by the transcriptional regulation of splicing factors.

Sociobiology meets oncology: unraveling altruistic cooperation in cancer cells and its implications.

Altruism, an act of benefiting others at a cost to the self, challenges our understanding of evolution. This Perspective delves into the importance of altruism in cancer cells and its implications for therapy. Against the backdrop of existing knowledge on various social organisms found in nature, we explore the mechanisms underlying the manifestation of altruism within breast tumors, revealing a complex interplay of seemingly counteracting cancer signaling pathways and processes that orchestrate the delicate balance between cost and benefit underlying altruistic cooperation.