Machine Learning-Driven Prediction, Preparation, and Evaluation of Functional Nanomedicines Via Drug-Drug Self-Assembly.

Small molecules as nanomedicine carriers offer advantages in drug loading and preparation. Selecting effective small molecules for stable nanomedicines is challenging. This study used artificial intelligence (AI) to screen drug combinations for self-assembling nanomedicines, employing physiochemical parameters to predict formation via machine learning.

Impact of Spinal Manipulative Therapy on Brain Function and Pain Alleviation in Lumbar Disc Herniation: A Resting-State fMRI Study.

Objective: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI).

Methods: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2).

Analysis of the causal relationship between gut microbiota and bone remodeling growth factor from the gene association.

Background: A growing body of evidence indicates a close association between the gut microbiota (GM) and the bone remodeling (BR) process, raising suspicions that the GM may actively participate in BR by modulating the levels of growth factors. However, the precise causal relationship between them remains unclear. Due to many confounding factors, many microorganisms related to BR growth factors have not been identified.

Brain effect mechanism of lever positioning manipulation on LDH analgesia based on multimodal MRI: a study protocol.

Introduction: The clinical symptoms of Lumbar Disc Herniation (LDH) can be effectively ameliorated through Lever Positioning Manipulation (LPM), which is closely linked to the brain's pain-regulating mechanisms. Magnetic Resonance Imaging (MRI) offers an objective and visual means to study how the brain orchestrates the characteristics of analgesic effects. From the perspective of multimodal MRI, we applied functional MRI (fMRI) and Magnetic Resonance Spectrum (MRS) techniques to comprehensively evaluate the characteristics of the effects of LPM on the brain region of LDH from the aspects of brain structure, brain function and brain metabolism.

A cell-permeable Ub-Dha probe for profiling E1-E2-E3 enzymes in live cells.

Activity-based ubiquitin probes (Ub-ABPs) have recently been developed as effective tools for studying the capabilities of E1-E2-E3 enzymes, but most of them can only be used in cell lysates. Here, we report the first cell-penetrating Ub-Dha probes based on thiazolidine-protected cysteines, which enable successful delivery into cells confirmed by a fluorophore at the N-terminus of Ub and live-cell fluorescence microscopy. A total of 18 E1-E2-E3 enzymes in live cells were labelled and enriched in combination with label-free quantification (LFQ) mass spectrometry.

Gene association analysis to determine the causal relationship between immune cells and juvenile idiopathic arthritis.

Background: Juvenile idiopathic arthritis (JIA) is a type of chronic childhood arthritis with complex pathogenesis. Immunological studies have shown that JIA is an acquired self-inflammatory disease, involving a variety of immune cells, and it is also affected by genetic and environmental susceptibility. However, the precise causative relationship between the phenotype of immune cells and JIA remains unclear to date.

A van der Waals p-n heterostructure of GaSe/SnS: a high thermoelectric figure of merit and strong anisotropy.

In recent years, van der Waals heterostructures (vdWHs) with controllable and peculiar properties have attracted extensive attention in the fields of electronics, optoelectronics, spintronics and electrochemistry. However, vdWHs with good thermoelectric performance are few due to the complex coupling of thermoelectric coefficients. Here, we employ density functional theory and Boltzmann's transport equation to explore the thermoelectric properties of the p-n vdWH of GaSe/SnS, which has been experimentally observed to exhibit high performance as an optoelectronic device.

Cell-Permeable Stimuli-Responsive Ubiquitin Probe for Time-Resolved Monitoring of Substrate Ubiquitination in Live Cells.

Dynamic monitoring of intracellular ubiquitin (Ub) conjugates is instrumental to understanding the Ub regulatory machinery. Although many biochemical approaches have been developed to characterize protein ubiquitination, chemical tools capable of temporal resolution probing of ubiquitination events remain to be developed. Here, we report the development of the first cell-permeable and stimuli-responsive Ub probe and its application for the temporal resolution profiling of ubiquitinated substrates in live cells.

How AI can learn from the law: putting humans in the loop only on appeal.

While the literature on putting a "human in the loop" in artificial intelligence (AI) and machine learning (ML) has grown significantly, limited attention has been paid to how human expertise ought to be combined with AI/ML judgments. This design question arises because of the ubiquity and quantity of algorithmic decisions being made today in the face of widespread public reluctance to forgo human expert judgment. To resolve this conflict, we propose that human expert judges be included via appeals processes for review of algorithmic decisions.

CISH impairs lysosomal function in activated T cells resulting in mitochondrial DNA release and inflammaging.

Chronic systemic inflammation is one of the hallmarks of the aging immune system. Here we show that activated T cells from older adults contribute to inflammaging by releasing mitochondrial DNA (mtDNA) into their environment due to an increased expression of the cytokine-inducible SH2-containing protein (CISH). CISH targets ATP6V1A, an essential component of the proton pump V-ATPase, for proteasomal degradation, thereby impairing lysosomal function.

T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection.

Antigen-specific, MHC-restricted αβ T cells are necessary for protective immunity against Mycobacterium tuberculosis, but the ability to broadly study these responses has been limited. In the present study, we used single-cell and bulk T cell receptor (TCR) sequencing and the GLIPH2 algorithm to analyze M. tuberculosis-specific sequences in two longitudinal cohorts, comprising 166 individuals with M.

Shear stress enhances anoikis resistance of cancer cells through ROS and NO suppressed degeneration of Caveolin-1.

Circulating tumor cells (CTCs) acquire enhanced anti-anoikis abilities after experiencing flow shear stress in the circulatory system. Our previous study demonstrated that low shear stress (LSS) promotes anoikis resistance of human breast carcinoma cells via caveolin-1 (Cav-1)-dependent extrinsic and intrinsic apoptotic pathways. However, the underlying mechanism how LSS enhanced Cav-1 expression in suspended cancer cells remains unclear.

A strain-induced considerable decrease of lattice thermal conductivity in 2D KAgSe with Coulomb interaction.

Based on first-principles calculations in combination with the Boltzmann transport theory, we investigate the effects of onsite Coulomb interaction and strain on the lattice thermal conductivity of the KAgSe monolayer, a recently discovered 2D thermoelectric system with a low lattice thermal conductivity when the onsite Coulomb interaction was not considered (X. Zhang, C. Liu, Y.

A High-Throughput Strategy for T-Cell Receptor Cloning and Expression.

Expression of T-cell receptor (TCR) genes is a critical step for TCR characterization and epitope identification. The recent interest in using specific TCRs for cancer immunotherapy has further increased the demand for practical and robust methods to rapidly clone and express TCRs. We show that a recombination-based cloning protocol facilitates simple and rapid transfer of the TCR transgene into different expression systems.

Effective photodegradation of rhodamine B and levofloxacin over CQDs modified BiOCl and BiOBr composite: Mechanism and toxicity assessment.

In this contribution, carbon quantum dots (CQDs) modified 3D-flower like BiOX (X = Cl, Br, I) photocatalyst were successfully prepared via a facile mechanical compounding method. The crystal structure, surface composition, morphologies, optical properties and photocatalytic activities were investigated in detail. The photocatalytic activity of the as-obtained photocatalyst were evaluated by degradation of rhodamine B (RhB) and Levofloxacin (LEV) under near IR-UV-vis light irradiation, the CQDs/BiOX composite displayed enhanced photocatalytic activity as compared with individual BiOX materials.

CRISPR-Cas12a System With Synergistic Phage Recombination Proteins for Multiplex Precision Editing in Human Cells.

The development of CRISPR-based gene-editing technologies has brought an unprecedented revolution in the field of genome engineering. Cas12a, a member of the Class 2 Type V CRISPR-associated endonuclease family distinct from Cas9, has been repurposed and developed into versatile gene-editing tools with distinct PAM recognition sites and multiplexed gene targeting capability. However, with current CRISPR/Cas12a technologies, it remains a challenge to perform efficient and precise genome editing of long sequences in mammalian cells.

Internet False News Information Feature Extraction and Screening Based on 5G Internet of Things Combined with Passive RFID.

In this paper, the authenticity of news information on the 5G Internet of Things (IoT) is studied, and a network false news information screening platform is designed and optimized by IoT combined with passive RFID. The electronic license chain based on data sovereignty is established, in which, combined with the identity identification and strong correlation ability based on the electronic license chain, a cross-industry, cross-business, and cross-field behavior record base database is formed; then, a digital library is constructed based on this base library; finally, through data sharing and management, a false news information feature extraction and screening platform is formed for the orderly management and reasonable dispatch of government resources and reducing various risks. The main functional modules implemented by the platform are the acquisition of news data and comment data, the retrieval and analysis of news data, the false detection of online news, and the visualization of false news data.

Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals.

The nutrient-sensing mammalian target of rapamycin (mTOR) is integral to cell fate decisions after T cell activation. Sustained mTORC1 activity favors the generation of terminally differentiated effector T cells instead of follicular helper and memory T cells. This is particularly pertinent for T cell responses of older adults who have sustained mTORC1 activation despite dysfunctional lysosomes.

Microbial single-strand annealing proteins enable CRISPR gene-editing tools with improved knock-in efficiencies and reduced off-target effects.

Several existing technologies enable short genomic alterations including generating indels and short nucleotide variants, however, engineering more significant genomic changes is more challenging due to reduced efficiency and precision. Here, we developed RecT Editor via Designer-Cas9-Initiated Targeting (REDIT), which leverages phage single-stranded DNA-annealing proteins (SSAP) RecT for mammalian genome engineering. Relative to Cas9-mediated homology-directed repair (HDR), REDIT yielded up to a 5-fold increase of efficiency to insert kilobase-scale exogenous sequences at defined genomic regions.

Identification of infectious spleen and kidney necrosis virus (ISKNV)-encoded microRNAs.

MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by complementary binding to target mRNAs. Virus-encoded miRNAs play important roles in virus life cycle and virus-host interactions. Viruses from the Megalocytivirus genus, family Iridoviridae, infect a wide range of fishes, bringing great challenges to aquaculture.

Shear stress stimulates integrin β1 trafficking and increases directional migration of cancer cells via promoting deacetylation of microtubules.

In egress routes of malignancy, cancer cells are constantly subjected to shear stress imposed by blood/lymph flow. Increasing evidence points toward the regulatory roles of shear stress in tumor cell adhesion and motility. Although it is known that integrin endocytic trafficking governs focal adhesion (FA) turnover and cell migration, the effect and biological consequences of low shear stress (LSS) on integrin trafficking remain unclear.

Matrix stiffness modulates ILK-mediated YAP activation to control the drug resistance of breast cancer cells.

One of the hallmarks of cancer progression is strong drug resistance during clinical treatments. The tumor microenvironment is closely associated with multidrug resistance, the optimization of tumor microenvironments may have a strong therapeutic effect. In this study, we configured polyacrylamide hydrogels of varying stiffness [low (10 kPa), intermediate (38 kPa) and high (57 kPa)] to simulate tissue physical matrix stiffness across different stages of breast cancer.

Re-localization of hormone effectors is associated with dormancy alleviation by temperature and after-ripening in sunflower seeds.

Temperature is the primary factor that affects seed dormancy and germination. However, the molecular mechanism that underlies its effect on dormancy alleviation remained largely unknown. In this study, we investigate hormone involvement in temperature induced germination as compared to that caused by after-ripening.

Activation of plasma membrane H-ATPases participates in dormancy alleviation in sunflower seeds.

Using various inhibitors and scavengers we took advantage of the size of sunflower (Helianthus annuus) seeds to investigate in vivo the effects of hormones, namely abscisic acid (ABA) and ethylene (ET), and reactive oxygen species (ROS) on the polarization of dormant (D) and non-dormant (ND) embryonic seed cells using microelectrodes. Our data show that D and ND seed cells present different polarization likely due to the regulation of plasma membrane (PM) H-ATPase activity. The data obtained after addition of hormones or ROS scavengers further suggest that ABA dependent inhibition of PM H-ATPases could participate in dormancy maintenance and that ET-and ROS-dependent PM H-ATPase stimulation could participate in dormancy release in sunflower seeds.