Spatially aligned graph transfer learning for characterizing spatial regulatory heterogeneity.

Spatially resolved transcriptomics (SRT) technologies facilitate the exploration of cell fates or states within tissue microenvironments. Despite these advances, the field has not adequately addressed the regulatory heterogeneity influenced by microenvironmental factors. Here, we propose a novel Spatially Aligned Graph Transfer Learning (SpaGTL), pretrained on a large-scale multi-modal SRT data of about 100 million cells/spots to enable inference of context-specific spatial gene regulatory networks across multiple scales in data-limited settings.

Extreme Tolerance of Nanoparticle-Protein Corona to Ultra-High Abundance Proteins Enhances the Depth of Serum Proteomics.

The serum nanoparticle-protein corona (NPC) provides specific disease information, thus opening a new avenue for high-throughput in-depth proteomics to facilitate biomarker discovery. Yet, little is known about the interactions between NPs and proteins, and its role in enhanced depth of serum proteomics. Herein, a series of protein spike-in experiments are conducted to systematically investigate protein depletion and enrichment during NPC formation.

High- organic-inorganic hybrid dielectric material for flexible thin-film transistors and printed logic circuits.

A new photopolymerizable organic-inorganic (O-I) hybrid sol-gel material, AUP@SiO-184, has been synthesized and utilized as a gate dielectric in flexible organic thin-film transistors (OTFTs). The previously reported three-arm alkoxy-functionalized silane amphiphilic polymer has yielded stable O-I hybrid materials comprising uniformly dispersed nanoparticles in the sol state. In this study, a photosensitizer was introduced, facilitating curing effects under ultraviolet light.

Potential roles of cigarette smoking on gut microbiota profile among Chinese men.

Background: Cigarette smoking is posited as a potential factor in disrupting the balance of the human gut microbiota. However, existing studies with limited sample size have yielded inconclusive results.

Methods: Here, we assessed the association between cigarette smoking and gut microbial profile among Chinese males from four independent studies (N total = 3308).

Genetic mapping of serum metabolome to chronic diseases among Han Chinese.

Serum metabolites are potential regulators for chronic diseases. To explore the genetic regulation of metabolites and their roles in chronic diseases, we quantified 2,759 serum metabolites and performed genome-wide association studies (GWASs) among Han Chinese individuals. We identified 184 study-wide significant (p < 1.

Biocomputing at the crossroad between emulating artificial intelligence and cellular supremacy.

Biocomputation aims to create sophisticated biological systems capable of addressing important problems in (bio)medicine with a machine-like precision. At present, computational gene networks engineered by single- or multi-layered assembly of DNA-, RNA- and protein-level gene switches have allowed bacterial or mammalian cells to perform various regulation logics of interest, including Boolean calculation or neural network-like computing. This review highlights the molecular building blocks, design principles, and computational tasks demonstrated by current biocomputers, before briefly discussing possible fields where biological computers may ultimately outcompete their electronic counterparts and achieve cellular supremacy.

Aptamer-based fluorescence biosensor for rapid detection of chloramphenicol based on pyrene excimer switch.

Chloramphenicol (CAP) is widely used in treating bacteria infection in animals and humans. However, the accumulation of CAP in food and environment caused serious health risk to human. Consequently, sensitive and selective detection of CAP is of great importance in environmental monitoring and food safety.

One-core neuron deep learning for time series prediction.

The enormous computational requirements and unsustainable resource consumption associated with massive parameters of large language models and large vision models have given rise to challenging issues. Here, we propose an interpretable 'small model' framework characterized by only a single core-neuron, i.e.

Unveiling the role of saltmarshes as coastal potassium sinks: A perspective from porewater-derived potassium exchange.

Saltmarshes serve as repositories for various metal species, primarily due to vegetation removal and mineralization processes. However, the significance of potassium (K), one of the three major nutrients (nitrogen, phosphorus, and K) essential for plant growth, has often been overlooked, particularly in the context of saltmarshes where the mechanisms of K transport via porewater exchange remain poorly understood. To address this knowledge gap, we conducted field observations and laboratory analysis, and developed a Rn mass balance model to quantify K fluxes via porewater exchange under physical, biological, and anthropogenic drivers.

Occurrence and migration of synthetic phenolic antioxidants in food packaging materials: Effects of plastic types and storage temperature.

Synthetic phenolic antioxidants (SPAs) are widely used in food packaging materials to extend product shelf life. Not much attention has been paid to high molecular weight SPAs (HMW SPAs) so far, despite their potential health risks. In this study, we first analyzed the concentrations of ten HMW SPAs in food plastic packaging materials (including 6 plastic categories, n = 116).

Synthesis of Unprotected Racemic Tryptophan Derivatives Using Gramine via Nickel(II) Complex.

A chemical method for the preparation of nonprotected tryptophan via nickel(II) complexes under simple operating conditions was established. The carefully designed nickel(II) glycinates are inexpensive and can be quantitatively recovered releasing the target tryptophans in high yield. The method has a wide range of synthesis generality, allowing the preparation of various substituted tryptophans.

Merging SOMO activation with transition metal catalysis: Deoxygenative functionalization of amides to β-aryl amines.

Singly occupied molecular orbital (SOMO) activation of in situ generated enamines has achieved great success in (asymmetric) α-functionalization of carbonyl compounds. However, examples on the use of this activation mode in the transformations of other functional groups are rare, and the combination of SOMO activation with transition metal catalysis is still less explored. In the area of deoxygenative functionalization of amides, intermediates such as iminium ions and enamines were often generated in situ to result in the formation of α-functionalized amines.

Advancements in molecular imaging probes for precision diagnosis and treatment of prostate cancer.

Prostate cancer is the second most common cancer in men, accounting for 14.1% of new cancer cases in 2020. The aggressiveness of prostate cancer is highly variable, depending on its grade and stage at the time of diagnosis.

Ultra-sensitive fluorescence-activated droplet single-cell sorting based on Tetramer-HCR-EvaGreen amplification.

The current single-cell analysis technologies such as fluorescence-activated cell sorting (FACS) and fluorescence-activated droplet sorting (FADS) could decipher the cellular heterogeneity but were constrained by low sorting performance and cell viability. Here, an ultra-sensitive single-cell sorting platform has been developed by integrating the FADS technology with Tetramer-HCR-EvaGreen (THE) fluorescence signal amplification. The THE system produced much higher fluorescence signal than that of the single Tetramer or Tetramer-HCR signal amplification.

Discovery of Novel RNA Demethylase FTO Inhibitors Featuring an Acylhydrazone Scaffold with Potent Antileukemia Activity.

Fat mass obesity-associated protein (FTO) has been emerging as a potential therapeutic target for drug discovery in RNA epigenetics. In this work, a series of novel FTO inhibitors featuring an acylhydrazone scaffold were identified, and the optimized compounds - showed potent FTO inhibitory activities with IC values ranging from 7.1 to 9.

Design, synthesis and activity evaluation of novel quinazolinone compounds as TRPC5 inhibitors.

The TRPC5 channel plays an important role in regulating various physiological processes, which is related to various human diseases, especially psychiatric and kidney diseases. Although the TRPC5 channel is one of the essential potential target, no drugs against TRPC5 channels have been granted in the market to date. In this study, based on the structure of hit compound ph1, we further synthesied 49 compounds of novel quinazolinone and heterocyclic fusion pyrimidinone derivatives, and their activities were evaluated by electrophysiological assays.

Achieving Biofunctional Micropatterns via Protein-Based Aqueous Photoresists with Tailored Functionalities.

Photolithography is the most widely used micropatterning technique at the micro- and nanoscale in device fabrication. However, traditional photoresists used in photolithography are typically nonaqueous-based toxic substances that require harsh conditions for processing, limiting the development of biofunctional and biocompatible micropatterns. In this study, a protein-based aqueous photoresist derived from chemically modified silk fibroin named SAMA, capable of achieving high-resolution micropatterning (<1.

A trigger-inducible split-Csy4 architecture for programmable RNA modulation.

The CRISPR-derived endoribonuclease Csy4 is a popular tool for controlling transgene expression in various therapeutically relevant settings, but adverse effects potentially arising from non-specific RNA cleavage remains largely unexplored. Here, we report a split-Csy4 architecture that was carefully optimized for in vivo usage. First, we separated Csy4 into two independent protein moieties whose full catalytic activity can be restored via various constitutive or conditional protein dimerization systems.

Two-dimensional Health State Map to define metabolic health using separated static and dynamic homeostasis features: a proof-of-concept study.

Defining metabolic health is critical for the earlier reversing of metabolic dysfunction and disease, and fasting-based diagnosis may not adequately assess an individual's metabolic adaptivity under stress. We constructed a novel Health State Map (HSM) comprising a Health Phenotype Score (HPS) with fasting features alone and a Homeostatic Resilience Score (HRS) with five time-point features only ( = 30, 60, 90, 180, 240 min) following a standardized mixed macronutrient tolerance test (MMTT). Among 111 Chinese adults, when the same set of fasting and post-MMTT data as for the HSM was used, the mixed-score was highly correlated with the HPS.

Chemical imaging unveils mitochondria as the major site of medicinal biguanide accumulation within cells.

Metformin (MET), a commonly prescribed medication for managing type 2 diabetes, has demonstrated various beneficial effects beyond its primary anti-diabetic efficacy. However, the mechanism underlying MET activity and its distribution within organelles remain largely unknown. In this study, we integrate multiple technologies, including chemical labeling, immunostaining, and high-resolution microscopy imaging, to visualize the accumulation of MET in organelles of cultured cells.

Bi-targeting of thioredoxin 1 and telomerase by thiotert promotes cell death of myelodysplastic syndromes and lymphoma.

Thioredoxin1 (TRX1) and telomerase are both attractive oncology targets that are tightly implicated in tumor initiation and development. Here, we reported that the 6-dithio-2-deoxyguanosine analog thiotert exhibits an effective cytotoxic effect on myelodysplastic syndromes (MDS) cell SKM-1 and lymphoma cell U-937. Further studies confirmed that thiotert effectively disrupts cellular redox homeostasis, as evidenced by elevated intracellular reactive oxygen species (ROS) levels, increased MnSOD, accelerated DNA impairment, and activated apoptosis signal.

Gut know-how: IL-22 from T cells boosts stress resilience.

Immune activation during sustained stress typically worsens stress-related psychopathology. Whether it can enhance stress resilience remains unclear. In this issue of Immunity, Xia, Lu, Lan et al.

Nonlinear memristive computational spectrometer.

In the domain of spectroscopy, miniaturization efforts often face significant challenges, particularly in achieving high spectral resolution and precise construction. Here, we introduce a computational spectrometer powered by a nonlinear photonic memristor with a WSe homojunction. This approach overcomes traditional limitations, such as constrained Fermi level tunability, persistent dark current, and limited photoresponse dimensionality through dynamic energy band modulation driven by palladium (Pd) ion migration.

Interfacial mechanisms of enhanced photoluminescence in AgI-doped red light emitting perovskite quantum dot glass.

Red light emitting perovskite quantum dot (PQD) glass, with narrow-band emission and excellent stability, holds great potential for applications in liquid crystal displays. However, its low photoluminescence quantum yield (PLQY) remains the biggest obstacle limiting its practical application. Additionally, the mechanism behind the enhancement of the PLQY is not well understood, which restricts the further improvement of the PLQY in red light emitting PQD glass.