Nanorobots mediated drug delivery for brain cancer active targeting and controllable therapeutics.

Brain cancer pose significant life-threats by destructively invading normal brain tissues, causing dysneuria, disability and death, and its therapeutics is limited by underdosage and toxicity lying in conventional drug delivery that relied on passive delivery. The application of nanorobots-based drug delivery systems is an emerging field that holds great potential for brain cancer active targeting and controllable treatment. The ability of nanorobots to encapsulate, transport, and supply therapies directly to the lesion site through blood-brain barriers makes it possible to deliver drugs to hard-to-reach areas.

YTHDF2 upregulation and subcellular localization dictate CD8 T cell polyfunctionality in anti-tumor immunity.

RNA methylation is an important regulatory process to determine immune cell function but how it affects the anti-tumor activity of CD8 T cells is not fully understood. Here we show that the N-methyladenosine (mA) RNA reader YTHDF2 is highly expressed in early effector or effector-like CD8 T cells. We find that YTHDF2 facilitates nascent RNA synthesis, and mA recognition is fundamental for this distinctively nuclear function of the protein, which also reinforces its autoregulation at the RNA level.

Activity-Based Dicyanoisophorone Derivatives: Fluorogenic Toolbox Enables Direct Visualization and Monitoring of Esterase Activity in Tumor Models.

The visualization and spatiotemporal monitoring of endogenous esterase activity are crucial for clinical diagnostics and treatment of liver diseases. Our research adopts a novel substrate hydrolysis-enzymatic activity (SHEA) approach using dicyanoisophorone-based fluorogenic ester substrates ) to evaluate esterase preferences on diverse substrate libraries. Esterase-mediated hydrolysis yielded fluorescent with a nanomolar detection limit .

ABHD5 as a friend or an enemy in cancer biology?

Alpha beta hydrolase domain containing 5 (ABHD5) is an essential coactivator of adipose triglyceride lipase (ATGL), a rate-limiting enzyme in various cell types that promotes the hydrolysis of triacylglycerol (TG) into diacylglycerol (DG) and fatty acid (FA). It acts as a critical regulatory factor in cellular lipid metabolism. The reprogramming of lipid metabolism is one of the hallmarks of cancer, suggesting that altering lipid metabolism could become a new strategy for tumor treatment.

Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy.

Drug discovery is a sophisticated process that incorporates scientific innovations and cutting-edge technologies. Compared to traditional bioactivity-based screening methods, encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency, throughput, and resource minimization. This review systematically summarizes the development history, typology, and prospective applications of encoding and displayed technologies, including phage display, ribosomal display, mRNA display, yeast cell display, one-bead one-compound, DNA-encoded, peptide nucleic acid-encoded, and new peptide-encoded technologies, and examples of preclinical and clinical translation.

Supercritical Fluids: An Innovative Strategy for Drug Development.

Nanotechnology plays a pivotal role in the biomedical field, especially in the synthesis and regulation of drug particle size. Reducing drug particles to the micron or nanometer scale can enhance bioavailability. Supercritical fluid technology, as a green drug development strategy, is expected to resolve the challenges of thermal degradation, uneven particle size, and organic solvent residue faced by traditional methods such as milling and crystallization.

Medium acidosis drives cardiac differentiation during mesendoderm cell fate specification from human pluripotent stem cells.

Effective lineage-specific differentiation is essential to fulfilling the great potentials of human pluripotent stem cells (hPSCs). In this report, we investigate how modulation of medium pH and associated metabolic changes influence mesendoderm differentiation from hPSCs. We show that daily medium pH fluctuations are critical for the heterogeneity of cell fates in the absence of exogenous inducers.

ERK5 promotes autocrine expression to sustain mitogenic balance for cell fate specification in human pluripotent stem cells.

The homeostasis of human pluripotent stem cells (hPSCs) requires the signaling balance of extracellular factors. Exogenous regulators from cell culture medium have been widely reported, but little attention has been paid to the autocrine factor from hPSCs themselves. In this report, we demonstrate that extracellular signal-related kinase 5 (ERK5) regulates endogenous autocrine factors essential for pluripotency and differentiation.

OGG1: An emerging multifunctional therapeutic target for the treatment of diseases caused by oxidative DNA damage.

Oxidative DNA damage-related diseases, such as incurable inflammation, malignant tumors, and age-related disorders, present significant challenges in modern medicine due to their complex molecular mechanisms and limitations in identifying effective treatment targets. Recently, 8-oxoguanine DNA glycosylase 1 (OGG1) has emerged as a promising multifunctional therapeutic target for the treatment of these challenging diseases. In this review, we systematically summarize the multiple functions and mechanisms of OGG1, including pro-inflammatory, tumorigenic, and aging regulatory mechanisms.

Enhanced anticancer effect of lysozyme-functionalized metformin-loaded shellac nanoparticles on a 3D cell model: role of the nanoparticle and payload concentrations.

Here we used a 3D human hepatic tumour cell culture model to assess the efficacy of "active" metformin-loaded nanoparticles (NPs) as anticancer therapeutics. The metformin nanocarrier design was repurposed from previous studies targeting bacterial and fungal biofilms with antimicrobials loaded in protease-coated nanoparticles. These active nanocarriers were constructed with shellac cores loaded with metformin as the anticancer agent and featured a surface coating of the cationic protease lysozyme.

Permutation conditional mutual information to quantify TMS-evoked cortical connectivity in disorders of consciousness.

To improve the understanding and diagnostic accuracy of disorders of consciousness (DOC) by quantifying transcranial magnetic stimulation (TMS) evoked electroencephalography connectivity using permutation conditional mutual information (PCMI).PCMI can characterize the functional connectivity between different brain regions. This study employed PCMI to analyze TMS-evoked cortical connectivity (TEC) in 154 DOC patients and 16 normal controls, focusing on optimizing parameter selection for PCMI (Data length, Order length, Time delay).

A novel indicator of anthropogenic influence on the fluctuability and stability of phytoplankton community composition.

Marine community composition is expected to be relatively stable in a natural environment over time but shift under increasing anthropogenic disturbances. In coastal waters, diatoms and dinoflagellates are two dominant phytoplankton functional groups. In this study, we developed an areal phytoplankton community composition index (APCI) that is based on the area of a scatter plot of dinoflagellate abundance (y-axis) vs diatom abundance (x-axis) using a time window of 1 year, 2 years or 3 years data.

CRISPR-Cas and CRISPR-based screening system for precise gene editing and targeted cancer therapy.

Target cancer therapy has been developed for clinical cancer treatment based on the discovery of CRISPR (clustered regularly interspaced short palindromic repeat) -Cas system. This forefront and cutting-edge scientific technique improves the cancer research into molecular level and is currently widely utilized in genetic investigation and clinical precision cancer therapy. In this review, we summarized the genetic modification by CRISPR/Cas and CRISPR screening system, discussed key components for successful CRISPR screening, including Cas enzymes, guide RNA (gRNA) libraries, target cells or organs.

A remote-controlled portable workstation for highly sensitive and real-time chemiluminescent detection of cadmium.

The prevention of pollution requires real-time monitoring of cadmium (Cd) concentration in the food, as it has a dramatic impact on poultry and can pose a threat to human health. Here, we fabricate a portable workstation integrating a microfluidic chip that facilitates real-time monitoring of Cd levels in real samples by utilizing the Luminol-KMnO chemiluminescence (CL) system. Interestingly, Cd can significantly enhance the CL signal, resulting in sensitive detection of Cd in the range of 0-0.

Enhanced Mechanical Strength and Sustained Drug Release in Carrier-Free Silver-Coordinated Anthraquinone Natural Antibacterial Anti-Inflammatory Hydrogel for Infectious Wound Healing.

The persistent challenge of healing infectious wounds and the rise of bacterial resistance represent significant hurdles in contemporary medicine. In this study, based on the natural small molecule drug Rhein self-assembly to form hydrogels and coordinate assembly with silver ions (Ag), a sustained-release carrier-free hydrogel with compact structure is constructed to promote the repair of bacterial-infected wounds. As a broad-spectrum antimicrobial agent, Ag can avoid the problem of bacterial resistance caused by the abuse of traditional antibiotics.

A scaffold vaccine to promote tumor antigen cross-presentation sustained toll-like receptor-2 (TLR2) activation.

Cancer vaccination holds great promise for cancer treatment, but its effectiveness is hindered by suboptimal activation of CD8 cytotoxic T lymphocytes, which are potent effectors to mediate anti-tumor immune responses. A possible solution is to switch antigen-presenting cells to present tumor antigens the major histocompatibility complex class I (MHC-I) to CD8 T cells - a process known as cross-presentation. To achieve this goal, we develop a three-dimensional (3D) scaffold vaccine to promote antigen cross-presentation by persisted toll-like receptor-2 (TLR2) activation after one injection.

Chip-based automated equipment for dual-mode point-of-care testing foodborne pathogens.

Foodborne pathogens have a substantial bearing on food safety and environmental health. The development of automated, portable and compact devices is essential for the on-site and rapid point-of-care testing (POCT) of bacteria. Here, this work developed a micro-automated microfluidic device for detecting bacteria, such as Escherichia coli (E.

Artemisinin Confers Cytoprotection toward Hydrogen Peroxide-Induced Cell Apoptosis in Retinal Pigment Epithelial Cells in Correlation with the Increased Acetylation of Histone H4 at Lysine 8.

Increased oxidative stress is one of the critical pathologies inducing age-related macular degeneration (AMD), characterized by retinal pigment epithelial (RPE) cell damage and death. The unbalanced acetylation and deacetylation of histones have been implicated in AMD pathogenesis or hydrogen peroxide (HO)-induced cell damage. Therefore, strategies aimed at controlling the balance between acetylation and deacetylation may effectively protect RPE cells from oxidative damage.

Interplay of Adolescents' and Parents' Mindsets of Socioeconomic Status on Adolescents' Stress-Related Outcomes.

The reciprocity and variation of values and beliefs are dynamic features of the parent-child relationship. Parents and adolescents may hold congruent or incongruent views regarding the malleability of socioeconomic status (mindset of SES), potentially influencing adolescents' psychological and physiological stress outcomes, as reflected in stress perceptions and the hypothalamic-pituitary-adrenal (HPA) axis functioning. The current study investigated how patterns of parent-adolescent congruence and incongruence in mindset of SES were associated with adolescents' perceived stress and diurnal cortisol patterns four months later.