Deciphering the unique autoregulatory mechanisms and substrate specificity of the understudied DCLK3 kinase linked to neurodegenerative diseases.

Protein kinases represent one of the largest and most druggable protein families. Despite considerable progress in their understanding, approximately one-third of human kinases remain poorly characterized, known as the "dark" kinome. Doublecortin-like kinase 3 (DCLK3), a member of this elusive group, has emerged for its involvement in neuroprotection in Huntington's disease and other neurodegenerative disorders.

Keratin 15 promotes tumor growth, invasion, epithelial-mesenchymal transition and radioresistance but represses ferroptosis via a Wnt/β-catenin signaling-related way in breast cancer.

Keratin 15 (KRT15) promotes tumor progression in several cancers, but its engagement in breast cancer is seldom uncovered. This study aimed to explore the impact of KRT15 modification on breast cancer growth, mobility, radiosensitivity, ferroptosis, and Wnt/β-catenin signaling pathway. A lentiviral vector containing short hairpin RNA or complementary DNA targeting KRT15 was transfected into MDA-MB-231 and MCF-7 cells in vitro.

Integrated phenomic and genomic analyses unveil modes of altered phenotypic plasticity during wheat improvement.

Background: Wheat has a critical role in global food security. During the improvement of wheat from landraces to cultivars, a suite of traits has been modified for higher yields. However, changing patterns of wheat in response to different environmental conditions, or phenotypic plasticity, during this improvement remain to be elucidated.

Holistic regulation of the diabetic osteo-microenvironment via NIR-II nanocarriers with dual NO/pH responsiveness for enhanced bone regeneration.

Diabetic conditions impair bone regeneration due to dysregulated macrophage polarization and inflammatory imbalance. Current therapies often fail to address systemic immune homeostasis. Herein, a bone-targeted nanoplatform (abbreviated as AgSr-MSNs) is engineered to scavenge excess nitric oxide (NO) and respond to the acidic diabetic microenvironment based on upregulated inducible nitric oxide synthase (iNOS) expression in M1 macrophages residing within both the diabetic bone marrow and localized osteolytic regions in our study.

Effect of the new fixed-time artificial insemination technology based on novel hormone preparations in gilts.

This study evaluated the effect of a novel fixed-time artificial insemination (FTAI) protocol for gilts, which incorporates altrenogest tablets (ALT-T), long-acting recombinant porcine FSH (rpFSH), and recombinant hCG (rhCG). A total of 160 gilts were divided into the control (n = 80) and the new treatment (n = 80) groups. Control gilts received oral altrenogest solution (20 mg/day) for 18 days, followed by 1000 IU equine chorionic gonadotropin (eCG) administered 42 h post-treatment and 100 μg GnRH 80 h later.

Applications of generative artificial intelligence in outcome prediction in intensive care medicine-a scoping review.

When a patient survives the first 24 h in intensive care, outcome prediction is crucial for further treatment decisions. As recent advances have shown that Artificial Intelligence (AI) outperforms clinicians in prognostication, and especially generative AI has developed rapidly in the past ten years, this scoping review aimed to explore the use of generative AI models for outcome prediction in intensive care medicine. Of the 481 records found in the search, 119 studies were subjected to abstract screening and, when necessary, full-text review for eligibility assessment.

Miniaturized MgBi-based thermoelectric cooler for localized electronic thermal management.

Miniaturized thermoelectric coolers, known for their high cooling power density and rapid thermal response, hold promise for localized thermal management. While traditional thermoelectric coolers have primarily relied on BiTe alloys, the recent development of n-type MgBi-based materials presents a compelling alternative, offering enhanced cost-effectiveness and environmental sustainability. In this study, we have designed and fabricated a MgBi-based miniscale thermoelectric cooler.

Injectable HMME-Loading Emulsion Hydrogel for Ultrasound-Triggered Release and Enhanced Sonodynamic Immunotherapy.

Immune checkpoint blockade (ICB) therapies, such as targeting programmed death-1 (PD-1) and programmed cell death protein ligand-1 (PD-L1), are often ineffective in low-immunogenic tumors, limiting their widespread use. In this study, an emulsion hydrogel is developed to encapsulate the sonosensitizer hematoporphyrin monomethyl ether (HMME), aimed at enhancing sonodynamic immunotherapy for low-immunogenic cancers. The water-in-oil emulsion hydrogel, characterized by its shear-thinning rheological properties, demonstrates excellent ultrasound (US)-triggered and lipase-triggered release, followed by sustained release.

Identification of the Novel HLA-DRB4*01:03:38 Allele in a Chinese Individual Using PacBio HiFi Sequencing.

HLA-DRB4*01:03:38 differs from HLA-DRB4*01:03:01:01 by one nucleotide substitution at position 42 (G → A) in exon 1.

Robotic Arm Trajectory Planning in Dynamic Environments Based on Self-Optimizing Replay Mechanism.

In complex dynamic environments, robotic arms face multiple challenges such as real-time environmental changes, high-dimensional state spaces, and strong uncertainties. Trajectory planning tasks based on deep reinforcement learning (DRL) suffer from difficulties in acquiring human expert strategies, low experience utilization (leading to slow convergence), and unreasonable reward function design. To address these issues, this paper designs a neural network-based expert-guided triple experience replay mechanism (NETM) and proposes an improved reward function adapted to dynamic environments.

Peritransplant lysine methyltransferase 2a-rearranged measurable residual disease dynamics as a prognostic marker in adult acute myeloid leukemia.

Background: This study examined the impact of measurable residual disease (MRD) dynamics in adults with lysine methyltransferase 2a rearrangement (KMT2Ar) in acute myeloid leukemia (AML) during the peritransplant period (before and early after allogeneic hematopoietic stem cell transplantation [HSCT]).

Methods: This study involved 144 adult patients with AML with KMT2Ar who underwent HSCT between 2015 and 2024. Patients were enrolled if they survived without relapse for at least 3 months post-HSCT.

Explainable ensemble learning for predicting pine wilt disease spread.

The rapid global spread of Pine Wilt Disease (PWD) has resulted in considerable ecological and economic losses, underscoring the necessity for precise forecasts of its future dissemination as a pivotal element in the control of the disease. In contrast to traditional semi-empirical models, which are unable to be applied to the increasing number of outbreak areas, machine learning (ML) models are better able to capture the hidden patterns of PWD spread. However, ML models have poor interpretability, and the imbalance between infected and potentially infected samples, coupled with the high dimensionality of the influencing factors, makes it challenging for any single ML model to achieve satisfactory performance.

The effect of maternal pre-pregnancy body mass index on hypertensive disorders of pregnancy (HDP): a systematic review and dose-response meta-analysis of cohort studies involving 50 million pregnancies.

Background: Hypertensive disorders of pregnancy is a prevalent pregnancy complication worldwide, and the dose-response association between maternal pre-pregnancy body mass index (BMI) and hypertensive disorders of pregnancy has not been precisely studied. The aim of this study was to assess dose-response association between maternal pre-pregnancy BMI and hypertensive disorders of pregnancy, including pregnancy induced hypertension, preeclampsia and eclampsia.

Methods: This dose-response meta-analysis searched four electronic databases (Pubmed, Web of science, OVID Embase and OVID Medline) for relevant publications up to October, 2023.

The role of subgenome expression dominance and DNA methylation in the heterodichogamy of Juglans mandshurica.

Heterodichogamy enhances species diversity and adaptability by reducing inbreeding depression and sexual interference in plants. However, its epigenetic molecular basis remains underexplored. We identified 1877 potential heterodichogamy-related genes (HRGs) in Juglans mandshurica Maxim.

Homotypic-Targeted Mineralized Tumor Cell Probes for Ultrasensitive MRI Diagnosis of Early-Stage Malignancies.

The effectiveness of clinically used magnetic resonance imaging (MRI) contrast agents (CAs) in tumor diagnosis is limited due to their low selectivity and sensitivity. To address this, we propose inactivated cell-based contrast agents (Mn-CCs) by constructing a mineralized tumor cell. Preserving proteins and structures on the cell membrane, Mn-CCs exhibit advantages, including homotypic targeting capabilities, tumor microenvironment (TME)-activated MRI signals, and ultrahigh relaxation rates.

DNA-Compatible Synthesis of Pyrrolidine-Fused Scaffolds via a One-Pot Three-Component Cycloaddition Strategy.

Pyrrolidines are privileged scaffolds commonly found in natural products, endowed with distinctive biological activities and significant pharmaceutical relevance. Herein, we describe a robust, DNA-compatible strategy for the efficient synthesis of pyrrolidine-fused scaffolds via a three-component cycloaddition of azomethine ylides. The resulting scaffolds, bearing reactive N-termini, can be further diversified using a range of reagents, thereby enhancing the chemical diversity of drug-like pyrrolidine-fused DNA-encoded library (DEL).

Phosphine Oxide-Induced Strong Emission and Multistimuli-Responsive Fluorochromism of -Carborane-Based Luminogens.

A series of -carborane-based triads, functionalized at the carbon vertices with diphenylphosphine groups (phosphine or phosphine oxide) as auxiliary groups and polycyclic aromatic moieties (naphthyl, phenanthryl, or pyrenyl) as donors, were successfully synthesized. The synergistic effects of phosphine and aromatic groups on the optoelectronic properties of -carborane-based luminescent molecules were studied. All of these compounds exhibit both locally excited (LE) emission and intramolecular charge transfer (ICT) emission, with the LE/ICT ratio and the occurrence of multiple emissions significantly influenced by the valence state of phosphorus and the steric hindrance of the aromatic rings.

Innate immune mechanisms hijacked by leukemia-initiating stem cells for selective advantage and immune evasion in Ptpn11-associated JMML.

Juvenile myelomonocytic leukemia (JMML) originates from mutated hematopoietic stem cells. The mechanism by which mutant stem cells are sustained, leading to leukemia development, remains elusive. By comprehensively examining transcriptomic profiles, cell compositions, developmental trajectories, and cell-cell interactions across various stages of tumor cell development in a mouse model of Ptpn11 mutation-associated JMML, we find that Ptpn11 mutant stem cells exhibit de novo activation of the myeloid transcriptional program and markedly increased expression of innate immunity-associated antimicrobial peptides and pro-inflammatory proteins, particularly S100a9 and S100a8.

An efficient ultrasound full-matrix imaging method in polar coordinate.

Circular measurement has found broad applications across medical and industrial domains. In the industrial field, total focus method (TFM) takes a superior position in full-matrix imaging methods, but conventional TFM efficiency has been restricted by computational complexity especially in multilayer structures. To improve the efficiency of full-matrix measurement, circular ultrasonic measurement was mathematically modeled in polar coordinate, and an efficient ultrasound full-matrix imaging method was proposed in this paper.

MRI-based quantification of primary ossification centers in the lateral and basilar parts of the human fetal occipital bone.

Background: The ossification of the occipital bone begins in the basilar part and progresses anteriorly, which is vital for the normal development of both the cranial and facial skeleton. Abnormal ossification of the occipital bone is associated with congenital anomalies such as Chiari malformation and anencephaly. Despite this, morphometric data on the ossification centers of the occipital bone, particularly in the lateral and basilar parts, remain limited.

Enhancing adversarial transferability via transformation inference.

The transferability of adversarial examples has become a crucial issue in black-box attacks. Input transformation techniques have shown considerable promise in enhancing transferability, but existing methods are often limited by their empirical nature, neglecting the wide spectrum of potential transformations. This may limit the transferability of adversarial examples.

RACK7 senses and fine-tunes enhancer activity.

Enhancers regulate dynamic gene expression in a spatiotemporal specific manner. A number of positive as well as negative regulators of enhancers have been reported so far. However, whether and how these regulators sense enhancer activity dynamics remains unclear.