Clinical Translation of Hyperpolarized C Metabolic Probes for Glioma Imaging.

Hyperpolarized carbon-13 (HP-C) MRI enables the real-time measurement of dynamic metabolism by utilizing molecular probes whose magnetization has been transiently enhanced via dynamic nuclear polarization of C labels. Based on pre-clinical and clinical investigations demonstrating Warburg-related metabolic dysfunction and tricarboxylic acid (TCA)-cycle alterations in gliomas, HPC techniques appear very promising for overcoming conventional challenges to evaluating tumor burden and extent, early therapeutic response and progression among patients non-invasively. This article surveys the multi-faceted translational development of HP-C MRI in the context of glioma imaging, while emphasizing innovation concerning the pharmacy production of HP probes - [1-C]/[2-C]-pyruvate and [1-C,5-C]-alpha-ketoglutarate - that serve as non-radioactive metabolic contrast agents.

A Preclinical Immunogenicity Study of the Recombinant Human Papillomavirus Nine-Valent Virus-like Particle Vaccine.

Background: Cervical cancer is associated with persistent infection of high-risk human papillomaviruses (HPVs). Prophylactic HPV vaccines have been recommended and have significant efficacy in preventing cervical cancer. Multivalent HPV vaccines have a better preventative effect on HPV-related diseases.

Specifically blocking αvβ8-mediated TGF-β signaling to reverse immunosuppression by modulating macrophage polarization.

Background: Targeting the TGF-β pathway in tumor therapy has proven challenging due to the highly context-dependent functions of TGF-β. Integrin αvβ8, a pivotal activator of TGF-β, has been implicated in TGF-β signaling within tumors, as demonstrated by the significant anti-tumor effects of anti-αvβ8 antibodies. Nevertheless, the expression profile of αvβ8 remains a subject of debate, and the precise mechanisms underlying the anti-tumor effects of anti-αvβ8 antibodies are not yet fully elucidated.

Increased Lateral Femoral Condyle Ratio Is Associated With a Greater Risk of Anterior Cruciate Ligament Injury and Concomitant Anterolateral Ligament and Meniscus Injuries.

Purpose: To investigate whether lateral femoral condyle ratio (LFCR) and lateral femoral condyle index (LFCI) were associated with a greater risk of anterior cruciate ligament (ACL) injury and concomitant injuries.

Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered on PROSPERO. PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to April 1, 2024.

Discovery of ZLC491 as a Potent, Selective, and Orally Bioavailable CDK12/13 PROTAC Degrader.

Selective degradation of cyclin-dependent kinases 12 and 13 (CDK12/13) emerges as a new potential therapeutic approach for triple-negative breast cancer (TNBC) and other human cancers. While several proteolysis-targeting chimera (PROTAC) degraders of CDK12/13 were reported, none are orally bioavailable. Here, we report the discovery of as a potent, selective, and orally bioavailable CDK12/13 PROTAC degrader.

Crucial time of emergency monitoring for reliable numerical pollution source identification.

The Pollution source identification (PSI) is an important issue on river water quality management especially for urban receiving water. Numerical inversion method is theoretically an effective PSI technique, which employs monitored downstream pollutant breakthrough curves to identify the pollution source. In practice, it is important to know how much monitoring data should be accumulated to provide PSI results with acceptable accuracy and uncertainty.

[Temporal variability of the isotope compositions of plum rain in Nanjing from event to interannual time scales].

Precipitation in the plum rain period accounts for 40%-50% of annual precipitation in the monsoon region. To clarify the temporal variability of the isotopic composition of precipitation during the plum rain period from event to interannual time scale and identify the influencing factors, we analyzed the isotopic composition of precipitation and its influencing factors in Nanjing from 2015 to 2022. By using the Hybrid Single-particle Lagran-gian Integrated Trajectory (HYSPLIT) model with specific humidity analysis, we investigated the water vapor source and influencing factors.

Comprehensive proteogenomic characterization of rare kidney tumors.

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes.

Unveiling the Pivotal Role of d Electronic States in Nickel-Based Hydroxide Electrocatalysts for Methanol Oxidation.

The anodic methanol oxidation reaction (MOR) plays a crucial role in coupling with the cathodic hydrogen evolution reaction (HER) and enables the sustainable production of the high-valued formate. Nickel-based hydroxide (Ni(OH)) as MOR electrocatalyst has attracted enormous attention. However, the key factor determining the intrinsic catalytic activity remains unknown, which significantly hinders the further development of Ni(OH) electrocatalyst.

Global, Regional, and National Burdens of Stroke in Children and Adolescents From 1990 to 2019: A Population-Based Study.

Background: Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels.

Methods: The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019.

Strain-Induced Self-Assembly at Interface of Two-Dimensional Heterostructures Boosts CO Reduction to Methanol by HO.

CO conversion with pure HO into CHOH and O driven by solar energy can supply fuels and life-essential substances for extraterrestrial exploration. However, the effective production of CHOH is significantly challenging. Here we report an organozinc complex/MoS heterostructure linked by well-defined zinc-sulfur covalent bonds derived by the structural deformation and intensive coupling of d(Zn)-p(S) orbitals at the interface, resulting in distinctive charge transfer behaviors and excellent redox capabilities as revealed by experimental characterizations and first-principle calculations.

Detecting bone marrow infiltration in nonosteolytic multiple myeloma through separation of hydroxyapatite via the two-material decomposition technique in spectral computed tomography.

Background: Conventional computed tomography (CT) has low sensitivity for the diagnosis of bone marrow infiltration in nonosteolytic multiple myeloma (NOL-MM). This study aimed to compare the performance of the two-material decomposition technique of spectral CT with the removal of X-ray absorption components of calcium (Ca) versus that of hydroxyapatite (HAP) for diagnosis of NOL-MM.

Methods: From October 2022 to March 2023, a total of 41 consecutive patients with MM without focal bone lesions undergoing chest spectral CT and thoracic spine magnetic resonance imaging (MRI) in Fujian Medical University Union Hospital were prospectively enrolled; meanwhile, another set of 41 age- and sex-matched healthy consecutive participants were selected as a comparison group.

Charge-Transfer-Induced Interfacial Ferromagnetism in Ferromagnet-Free Oxide Heterostructures.

Due to the strong interlayer coupling between multiple degrees of freedom, oxide heterostructures have demonstrated exotic properties that are not shown by their bulk counterparts. One of the most interesting properties is ferromagnetism at the interface formed between "nonferromagnetic" compounds. Here we report on the interfacial ferromagnetic phase induced in the superlattices consisting of the two paramagnetic oxides CaRuO (CRO) and LaNiO (LNO).

Improved Detection of Target Metabolites in Brain Tumors with Intermediate TE, High SNR, and High Bandwidth Spin-Echo Sequence at 5T.

Background And Purpose: Due to high chemical shift displacement, challenges emerge at ultra-high fields when measuring metabolites using H-MRS. Our goal was to investigate how well the high SNR and high bandwidth spin-echo (HISE) technique perform at 5T for detecting target metabolites in brain tumors.

Materials And Methods: Twenty-six subjects suspected of having brain tumors were enrolled.

Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy.

Background: Recently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression in the cardiovascular system after birth, SLIT3's relevance to cardiovascular function in the postnatal state remains unknown. As such, the objectives of this study were to determine the postnatal myocardial sources of SLIT3 and to evaluate its functional role in regulating the cardiac response to pressure overload stress.

Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations.

For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics.

Improving cardiovascular risk prediction through machine learning modelling of irregularly repeated electronic health records.

Aims: Existing electronic health records (EHRs) often consist of abundant but irregular longitudinal measurements of risk factors. In this study, we aim to leverage such data to improve the risk prediction of atherosclerotic cardiovascular disease (ASCVD) by applying machine learning (ML) algorithms, which can allow automatic screening of the population.

Methods And Results: A total of 215 744 Chinese adults aged between 40 and 79 without a history of cardiovascular disease were included (6081 cases) from an EHR-based longitudinal cohort study.

The Dynamic Evolution Model of the Chemical and Carbon Isotopic Composition of C during the Hydrocarbon Generation Process.

A new approach is presented in this paper for the dynamic modeling of the chemical and isotopic evolution of C during the hydrocarbon generation process. Based on systematic data obtained from published papers for the pyrolysis of various hydrocarbon sources (type I kerogen/source rock, type II kerogen/source rock, type III kerogen/source rock, crude oil, and asphalt, etc.), the empirical evolution framework of the chemical and isotopic composition of C during the hydrocarbon generation process was built.

Vaccine design via antigen reorientation.

A major challenge in creating universal influenza vaccines is to focus immune responses away from the immunodominant, variable head region of hemagglutinin (HA-head) and toward the evolutionarily conserved stem region (HA-stem). Here we introduce an approach to control antigen orientation via site-specific insertion of aspartate residues that facilitates antigen binding to alum. We demonstrate the generalizability of this approach with antigens from Ebola, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses and observe enhanced neutralizing antibody responses in all cases.

Quantifying the energy landscape in weakly and strongly disordered frictional media.

We investigate the "roughness" of the energy landscape of a system that diffuses in a heterogeneous medium with a random position-dependent friction coefficient α(x). This random friction acting on the system stems from spatial inhomogeneity in the surrounding medium and is modeled using the generalized Caldira-Leggett model. For a weakly disordered medium exhibiting a Gaussian random diffusivity D(x) = kBT/α(x) characterized by its average value ⟨D(x)⟩ and a pair-correlation function ⟨D(x1)D(x2)⟩, we find that the renormalized intrinsic diffusion coefficient is lower than the average one due to the fluctuations in diffusivity.

Targeting the heparan sulfate-binding site of RAGE with monoclonal antibodies.

Heparan sulfate (HS) plays its biological functions by interacting with hundreds of secreted extracellular and transmembrane proteins. Interaction with HS has been shown to be required for the normal function of many HS-binding proteins. Receptor for advanced glycation end-product (RAGE) is such a protein, whose activation requires HS-induced oligomerization.

N,S coordination in Ni single-atom catalyst promoting CORR towards HCOOH.

Carbon-based single atom catalysts (SACs) are attracting extensive attention in the CO reduction reaction (CORR) due to their maximal atomic utilization, easily regulated active center and high catalytic activity, in which the coordination environment plays a crucial role in the intrinsic catalytic activity. Taking NiN as an example, this study reveals that the introduction of different numbers of S atoms into N coordination (Ni-NS ( = 1-4)) results in outstanding structural stability and catalytic activity. Owing to the additional orbitals around -1.

Prenatal Nicotine Exposure Raises Male Blood Pressure via FTO-Mediated NOX2/ROS Signaling.

Background: Cigarette smoking/nicotine exposure in pregnancy shows an increased risk of hypertension in offspring, but the mechanisms are unclear. This study tested the hypothesis that m6A RNA hypomethylation epigenetically regulates vascular NOX (NADPH oxidase) and reactive oxygen species production, contributing to the fetal programming of a hypertensive phenotype in nicotine-exposed offspring.

Methods: Pregnant rats were exposed to episodic chronic intermittent nicotine aerosol (CINA) or saline aerosol control from gestational day 4 to day 21, and experiments were performed in 6-month-old adult offspring.