Targeted degradation of hexokinase 2 by a novel engineered bispecific chimeric liposome-based Nano-PROTACs for enhancing tumor chemotherapy.

Aerobic glycolysis is critical for tumor development and metastasis. Regulating the activity of vital metabolic enzymes in the tumor glycolysis process, such as hexokinase 2 (HK-2), is expected for tumor treatment. However, conventional small molecule inhibitors only block the activity of proteases with consistently high doses via occupation-driven pattern, leading to off-target effects which limit their clinical application.

Organophotoredox Cascade Cyclization for the Synthesis of Silyl/Fluoroalkylated Tetracyclic Pyrrolizidinediones.

A novel strategy for accessing unprecedented silyl/fluoroalkyl-embedded tetracyclic pyrrolizidinediones has been developed through the visible-light-induced cascade cyclization of 3-methyleneisoindolin-1-ones using hydrosilanes or fluoroalkylsulfinate salts as radical sources under redox-neutral conditions. This protocol features mild reaction conditions, operational simplicity, and excellent compatibility with various functional groups. A number of silyl/fluoromethyl-decorated tetracyclic pyrrolizidinedione frameworks were efficiently created.

A brain-wide map of neural activity during complex behaviour.

A key challenge in neuroscience is understanding how neurons in hundreds of interconnected brain regions integrate sensory inputs with previous expectations to initiate movements and make decisions. It is difficult to meet this challenge if different laboratories apply different analyses to different recordings in different regions during different behaviours. Here we report a comprehensive set of recordings from 621,733 neurons recorded with 699 Neuropixels probes across 139 mice in 12 laboratories.

Brain-wide representations of prior information in mouse decision-making.

The neural representations of prior information about the state of the world are poorly understood. Here, to investigate them, we examined brain-wide Neuropixels recordings and widefield calcium imaging collected by the International Brain Laboratory. Mice were trained to indicate the location of a visual grating stimulus, which appeared on the left or right with a prior probability alternating between 0.

Identification and validation of the cellular senescence-associated molecular pattern and diagnostic markers for osteoporosis.

Background: Osteoporosis is an age-related skeletal disorder with an increasing burden of osteoporotic fractures worldwide, it is urgent the identification of reliable molecular characteristics to prevent the progression of severe osteoporosis.

Methods: Two datasets were obtained from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) and selected the cellular senescence-related genes (SRGs). Consensus clustering analysis was performed based on differentially expressed SRGs (DE-SRGs).

Resolution assessment of super-resolution microscopy imaging: structural and technical dependencies for cell biology.

Super-resolution fluorescence microscopy (SRM) has enabled visualization of nanoscale cellular structures, but systematic evaluation of resolution assessment methods across diverse biological structures and SRM modalities remains lacking. Here, we comparatively assessed three resolution metrics-Full Width at Half Maximum (FWHM), decorrelation analysis, and Fourier Ring Correlation (FRC)-across two SRM techniques (Super-resolution Radial Fluctuation, SRRF; Stimulated Emission Depletion, STED) using key subcellular structures: microtubules (filaments), mitochondria (membranes), and nuclear pore protein Nup98 (single particles) in HeLa/U2OS cells. Our results showed decorrelation analysis provided robust resolution estimates across all structures and modalities (confocal/SRRF/STED), exhibiting superior performance for dense nuclear pore complexes where FWHM failed due to overlapping point spread functions.

Can household clean energy transition reduce medical expenditures? Evidence from China.

Indoor air pollution is a significant issue in developing nations, posing serious health risks and contributing to various diseases. Despite its importance, the relationship between household clean energy transition and its effects on health outcomes and medical expenses has received limited scholarly attention. This study addresses this gap by utilizing the Air Pollution Prevention and Control Action Plan (APCP), implemented by the State Council of China in 2013, as a policy intervention.

Exploring the Neuroprotective Properties of Musk against High-altitude Cerebral Edema: Unveiling the Mechanisms via TNF-α/RIPK1 Pathway Regulation and Necroptosis Inhibition.

Ethnopharmacological Relevance: Musk (Moschus Moschiferus) is regarded as a key drug for treating brain injury-related nerve damage in both traditional Chinese medicine and Tibetan medicine. According to the theory of traditional Chinese medicine, musk has the characteristics of being pungent and warm, and acts on the heart and spleen meridians, with the effects of awakening the brain and opening the orifices, as well as promoting blood circulation and removing blood stasis. This makes it an important drug for treating acute brain injuries such as closed coma and stroke with phlegm obstruction.

Iron overload promotes myeloid differentiation of normal hematopoietic stem cells and educates macrophage mediated immunosuppression in acute myeloid leukemia.

Background: The hematopoietic ecosystem comprises both cellular components such as hematopoietic stem cells (HSCs) and immune cells as well as non-cellular components including iron. Systemic iron overload, which leads to serious complications and affects both patients' quality of life and overall survival, is a common clinical challenge in patients with acute myeloid leukemia (AML). We previously elucidated the direct effects of iron overload on AML cells.

Lead-Free Halide Perovskite CsZrX Doped with Cr for Multifunctional X-ray and NIR Imaging.

Traditional X-ray imaging based on scintillators primarily provides structural insights but falls short of the capacity to resolve intricate biological features. In this work, we propose a multifunctional imaging strategy enabled by CsZrX:Cr halide perovskite that uniquely exhibits both efficient near-infrared (NIR) photoluminescence under UV excitation and intense radioluminescence under X-ray irradiation. The material presents a high light yield of 56,250 photons MeV and a NIR photoluminescence quantum yield (PLQY) of 62.

Low-Frequency (1 Hz) Repetitive Trans-Spinal Magnetic Stimulation Attenuates NLRP3-Driven Neuroinflammation and Enhances Motor Recovery in Spinal Cord-Injured Mice.

Purpose: Investigate the effects of repetitive Trans-Spinal Magnetic Stimulation (rTSMS) on motor function recovery and the underlying mechanisms in mice after spinal cord injury.

Methods: rTSMS was applied both in vivo and in vitro, Motor function was evaluated by the Basso Mouse Scale (BMS), grid walking errors, and Motor Evoked Potentials (MEPs). Cell viability, oxidative stress markers, and key proteins including AQP4, Bax, Bcl-2, cleaved caspase-3, inflammatory cytokines, and NLRP3 inflammasome components were analyzed.

A causal relationship between circulating immune cells, plasma metabolites, and pulmonary diseases: a mediated Mendelian randomization study.

Background: Immune cells and plasma metabolites may play important roles in the development of pulmonary diseases, but the relationship between different immune cells, plasma metabolites and various pulmonary diseases is still unclear. In this study, we aim to employ Mendelian randomization (MR) to investigate the causality between immune cells, pulmonary diseases and plasma metabolites.

Methods: We analyzed immune cells and seven pulmonary diseases, including interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), lung cancer, pneumonia, chronic obstructive pulmonary disease (COPD), sleep apnea syndrome (SAS), and tuberculosis (TB), using genome-wide association analysis (GWAS) data for immune cells as an exposure factor and seven lung diseases as outcomes.

Molecular expression of genes related to sex differentiation and their response to sex steroid hormones in the clam Chinese cyclina (Cyclina sinensis).

This study investigated the tissue-specific expression and subcellular localization of sex differentiation-related genes of Cyclina sinensis, and then analyzed the effects of hormone treatment (1 and 50 μg/L estradiol treatment (E-1, E-50), 1 and 50 μg/L testosterone (T-1, T-50), and a control group (C)) on the sex ratio, gonadosomatic index, hepatosomatic index, hormone content, and expression of sex differentiation-related genes of juvenile C. sinensis. Vitellogenin (Vg), testis-specific serine kinase 1 (Tssk1), doublesex and mab-3 related transcription factor 1 (Dmrt1), and Wnt family member 4 (Wnt4) were significantly expressed in the gonads of adult C.

Amphoteric coplanar conjugated molecules enabling efficient and stable perovskite/silicon tandem solar cells.

The perovskite/silicon tandem solar cells (TSCs) offers a state-of-the-art solution for achieving unparalleled efficiency and cost-effectiveness in solar energy conversion. However, the fabrication of high-quality wide-bandgap perovskite films with a thickness of 1 μm on nano-textured silicon substrates remains a formidable challenge. Herein, we designed an amphoteric coplanar conjugated molecule (ACCM) guided by the principles of density functional theory and Brønsted acid-base chemistry.

The role of magnesium hydrogels in bone regeneration: a systematic review and meta-analysis.

Magnesium, an essential element in human physiology, is predominantly located in bone tissue. Since the early 20th century, magnesium-based biomaterials have demonstrated osteoinductive and angiogenic potential, positioning them as promising candidates for bone regeneration strategies. Hydrogels, composed of crosslinked hydrophilic polymers, provide a three-dimensional microenvironment mimicking the extracellular matrix (ECM), thereby supporting cell adhesion, nutrient diffusion, and controlled release of bioactive ions such as Mg²⁺.

Induction immunochemotherapy followed by definitive chemoradiotherapy and consolidation immunotherapy for unresectable stage III non-small cell lung cancer: a multi-institutional retrospective cohort study.

Background: For unresectable stage III non-small cell lung cancer (NSCLC), the standard regimen is definitive concurrent chemoradiotherapy (CRT) followed by consolidation immunotherapy. We investigated whether incorporating induction immunochemotherapy enhances the efficacy.

Materials And Methods: From June 2018 to December 2022, 294 patients with unresectable stage III NSCLC were included, who did (162, I-CRT-I group) or did not (132, CRT-I group) receive induction immunochemotherapy, followed by definitive CRT and consolidation immunotherapy.

Clinical efficacy of azithromycin-budesonide combination therapy in pediatric Mycoplasma pneumoniae pneumonia.

Objective: To evaluate the clinical outcomes of adjunctive budesonide (BUD) therapy combined with azithromycin (AZM) in pediatric patients diagnosed with pneumonia (MPP).

Methods: This retrospective cohort analysis examined 120 pediatric MPP cases. Participants were stratified into either a control group (n=55, standard AZM treatment) or an observation group (n=65, AZM in combination with BUD) based on their treatment regimen.

Research on the impact of algorithmic trading on market volatility.

The rapid growing of algorithmic trading (AT) has been playing an increasingly important role in shaping financial market in recent years. Although many scholars have studied the impact of AT on market volatility, the evidence they provided is inconsistent. Whether and how AT influence on market volatility is still not clear, especially for emerging markets.

The m6A methyltransferase METTL14 promotes oncogenic Kras induced juvenile myelomonocytic leukemia through dysregulating autophagy.

The N6-methyladenosine (m6A) modification plays an important role in the pathogenesis of various myeloid malignancies. However, its specific role in RAS mutation-induced myeloid malignancy is incompletely understood. In this study, we found that m6A methyltransferase methyltransferase-like 14 (METTL14) was highly expressed and associated with a shorter survival in a RAS-mutation myeloid malignancy, juvenile myelomonocytic leukemia (JMML).

Integrative multi-omics analysis N4-acetylcytidine modification landscape and the role of TMEM65 in breast cancer.

N4-acetylcytidine (ac4C), an evolutionarily conserved RNA modification regulated by NAT10, is increasingly recognized for its role in post-transcriptional gene regulation. However, the modification patterns and clinical significance of ac4C remain largely unclear in breast cancer (BC). In this study, we performed single-cell transcriptomic analysis to investigate the heterogeneity of ac4C-related gene (acRG) activity within the BC microenvironment for the first time.

Familial spinocerebellar ataxia type 3: A case report of multi-generational presentation.

Rationale: Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, a rare autosomal dominant neurodegenerative disorder caused by cytosine-adenine-guanine repeat expansions in ATXN3, lacks effective therapies. This case report highlights the clinical and genetic features of a family with 5 affected members to emphasize the challenges in diagnosis, management, and the need for targeted therapies.

Patient Concerns: A 33-year-old male proband presented with progressive gait instability, limb incoordination, and dysarthria for more than 2 years.

Novel Self-Powered Biosensor Based on Highly Efficient Cosignal Accelerator and Multiple Signal Amplification Strategies toward Ultrasensitive miRNA-141 Assay.

A highly sensitive self-powered biosensor is designed based on gold-platinum nanorods (AuPt NRs) and the cascade reaction of catalytic hairpin assembly (CHA) and hybrid chain reaction (HCR) toward the miRNA-141 assay. As a cosignal accelerator, AuPt NRs enhance electrical conductivity between glucose oxidase (GOD) and a carbon paper (CP) electrode, thereby assisting in output signal enhancement. The cascade reaction of CHA-HCR is employed to efficiently amplify the detection signal and improve the sensitivity of the self-powered biosensor.

Two new cadinane-type sesquiterpene glycosides from .

Two novel and two previously identified cadinane-type sesquiterpene glycosides, findleyanosides E-F (-), balanoindicoside B () and pumilaside C (), were extracted from the stems. The establishment of structures was mainly conducted spectroscopic techniques and by comparing with literature data. Electronic circular dichroism (ECD) computations helped determine the absolute configuration of the novel molecules.

Clinical Outcomes of Patients With Advanced ALK-Rearranged Lung Squamous Cell Carcinoma Treated With ALK Tyrosine Kinase Inhibitors.

Background: DNA-based next-generation sequencing (NGS) has identified ALK rearrangements in lung squamous cell carcinoma (LUSC), a subset of nonsmall cell lung cancer traditionally lacking effective targeted therapies. While ALK tyrosine kinase inhibitors (TKIs) like crizotinib and alectinib are effective in ALK-rearranged lung adenocarcinoma, their efficacy in LUSC remains poorly defined due to limited subtype-specific data.

Methods: We presented a case of ALK-rearranged LUSC and established a patient-derived xenograft (PDX) model to validate the tumor-inhibitory effects of various ALK-TKIs on ALK-positive LUSC.

Quaternized chitosan-coated PLGA nanoparticles co-deliver resveratrol and all-trans retinoic acid to enhance humoral immunity, cellular immunity and gastrointestinal mucosal immunity.

Conventional vaccine adjuvants are limited by their mechanisms of action and administration routes, often failing to simultaneously elicit robust systemic and mucosal immune responses. This limitation compromises the establishment of dual protective barriers during early pathogen invasion. Therefore, we developed an innovative poly (lactic-co-glycolic acid) (PLGA) nanoparticle-based adjuvant system (Res/RA QCS NPs) featuring quaternized chitosan (QCS) surface modification for ovalbumin (OVA) delivery, co-encapsulating dual immunomodulators - resveratrol (Res) and all-trans retinoic acid (RA).