The landscape of histone modification in organ fibrosis.

An increase in fibrous connective tissue and a decrease in parenchymal cells in organ tissues are the primary pathological alterations linked to organ fibrosis. If fibrosis is not treated, organ structure is destroyed, function can decline, or even fail, posing a serious risk to human life and health. Numerous organs develop fibrosis, and organ fibroproliferative illnesses account for almost 45% of patient deaths from various diseases in the industrialized world, as well as a major cause of disability and mortality in many other diseases. Recently, it has become evident that histone modification is an important way to regulate gene expression in organ fibrosis. Histone modifications alter the structure of chromatin, thereby affecting gene accessibility. Histone acetylation modifications relax chromatin, making it easier for gene transcription factors to access DNA, thereby promoting gene transcription. In addition, histone modifications recruit other proteins to interact with chromatin to form complexes that further regulate gene expression. Histone methylation modifications recruit methylation-reading proteins that recognize methylation marks and alter gene expression status. It not only affects the normal physiological function of cells, but also plays an important role in organ fibrosis. This article reviews the important role played by histone modifications in organ fibrosis and potential therapeutic approaches.

Topical JAK inhibition ameliorates EGFR inhibitor-induced rash in rodents and humans.

Epidermal growth factor receptor inhibitors (EGFRis) are used to treat many cancers, but their use is complicated by the development of a skin rash that may be severe, limiting their use and adversely affecting patient quality of life. Most studies of EGFRi-induced rash have focused on the fully developed stage of this skin disorder, and early pathological changes remain unclear. We analyzed high-throughput transcriptome sequencing of skin samples from rats exposed to the EGFRi afatinib and identified that keratinocyte activation is an early pathological alteration in EGFRi-induced rash. Mechanistically, the induction of S100 calcium-binding protein A9 (S100A9) occurred before skin barrier disruption and led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells. Topical JAK inhibition suppressed the recruitment of immune cells and ameliorated the severity of skin rash in afatinib-treated rats and mice with epidermal deletion of EGFR, while having no effect on EGFRi efficacy in tumor-bearing mice. In a pilot clinical trial (NCT05120362), 11 patients with EGFRi-induced rash were treated with delgocitinib ointment, resulting in improvement in rash severity by at least one grade in 10 of them according to the MASCC EGFR inhibitor skin toxicity tool (MESTT) criteria. These findings provide a better understanding of the early pathophysiology of EGFRi-induced rash and suggest a strategy to manage this condition.

Concomitant Near-Infrared Photothermy and Photoluminescence of Rod-Shaped Au52(PET)32 and Au66(PET)38 Synthesized Concurrently.

Gold nanoclusters exhibiting concomitant photothermy (PT) and photoluminescence (PL) under near-infrared (NIR) light irradiation are rarely reported, and some fundamental issues remain unresolved for such materials. Herein, we concurrently synthesized two novel rod-shaped Au nanoclusters, Au52(PET)32 and Au66(PET)38 (PET = 2-phenylethanethiol), and precisely revealed that their kernels were 4 × 4 × 6 and 5 × 4 × 6 face-centered cubic (fcc) structures, respectively, based on the numbers of Au layers in the [100], [010], and [001] directions. Following the structural growth mode from Au52(PET)32 to Au66(PET)38, we predicted six more novel nanoclusters. The concurrent synthesis provides rational comparison of the two nanoclusters on the stability, absorption, emission and photothermy, and reveals the aspect ratio-related properties. An interesting finding is that the two nanoclusters exhibit concomitant PT and PL under 785 nm light irradiation, and the PT and PL are in balance, which was explained by the qualitative evaluation of the radiative and non-radiative rates. The ligand effects on PT and PL were also investigated.

Degradation and enhanced oil recovery potential of Alcanivorax borkumensis through production of bio-enzyme and bio-surfactant.

Microbial enhanced oil recovery (EOR) has become the focus of oilfield research due to its low cost, environmental friendliness and sustainability. The degradation and EOR capacity of A. borkumensis through the production of bio-enzyme and bio-surfactant were first investigated in this study. The total protein concentration, acetylcholinesterase, esterase, lipase, alkane hydroxylase activity, surface tension, and emulsification index (EI) were determined at different culture times. The bio-surfactant was identified as glycolipid compound, and the yield was 2.6 ± 0.2 g/L. The nC12 and nC13 of crude oil were completely degraded, and more than 40.0 % of nC14-nC24 was degraded by by A. borkumensis. The results of the microscopic etching model displacement and core flooding experiments showed that emulsification was the main mechanism of EOR. A. borkumensis enhanced the recovery rate by 20.2 %. This study offers novel insights for the development of environmentally friendly and efficient oil fields.

Atomically Precise Nanometer-Sized Pt Catalysts with an Additional Photothermy Functionality.

Atomically precise ~1-nm Pt nanoparticles (nanoclusters, NCs) with ambient stability are important in fundamental research and exhibit diverse practical applications (catalysis, biomedicine, etc.). However, synthesizing such materials is challenging. Herein, by employing the mixture ligand protecting strategy, we successfully synthesized the largest organic-ligand-protected (~1-nm) Pt23 NCs precisely characterized with mass spectrometry and single-crystal X-ray diffraction analyses. Interestingly, natural population analysis and Bader charge calculation indicate an alternate, varying charge -layer distribution in the sandwich-like Pt23 NC kernel. Pt23 NCs can catalyze the oxygen reduction reaction under acidic conditions without requiring calcination and other treatments, and the resulting specific and mass activities without further treatment are sevenfold and eightfold higher than those observed for commercial Pt/C catalysts, respectively. Density functional theory and d-band center calculations interpret the high activity. Furthermore, Pt23 NCs exhibit a photothermal conversion efficiency of 68.4 % under 532-nm laser irradiation and can be used at least for six cycles, thus demonstrating great potential for practical applications.

Bottom-Up Construction of Metal-Organic Framework Loricae on Metal Nanoclusters with Consecutive Single Nonmetal Atom Tuning for Tailored Catalysis.

The introduction of single or multiple heterometal atoms into metal nanoparticles is a well-known strategy for altering their structures (compositions) and properties. However, surface single nonmetal atom doping is challenging and rarely reported. For the first time, we have developed synthetic methods, realizing "surgery"-like, successive surface single nonmetal atom doping, replacement, and addition for ultrasmall metal nanoparticles (metal nanoclusters, NCs), and successfully synthesized and characterized three novel bcc metal NCs Au38I(S-Adm)19, Au38S(S-Adm)20, and Au38IS(S-Adm)19 (S-Adm: 1-adamantanethiolate). The influences of single nonmetal atom replacement and addition on the NC structure and optical properties (including absorption and photoluminescence) were carefully investigated, providing insights into the structure (composition)-property correlation. Furthermore, a bottom-up method was employed to construct a metal-organic framework (MOF) on the NC surface, which did not essentially alter the metal NC structure but led to the partial release of surface ligands and stimulated metal NC activity for catalyzing p-nitrophenol reduction. Furthermore, surface MOF construction enhanced NC stability and water solubility, providing another dimension for tunning NC catalytic activity by modifying MOF functional groups.

Single-cell transcriptomic analysis of radiation-induced lung injury in rat.

Radiation-induced lung injury (RILI) frequently occurs as a complication following radiotherapy for chest tumors like lung and breast cancers. However, the precise underlying mechanisms of RILI remain unclear. In this study, we generated RILI models in rats treated with a single dose of 20 Gy and examined lung tissues by single-cell RNA sequencing (scRNA-seq) 2 weeks post-radiation. Analysis of lung tissues revealed 18 major cell populations, indicating an increase in cell-cell communication following radiation exposure. Neutrophils, macrophages, and monocytes displayed distinct subpopulations and uncovered potential for pro-inflammatory effects. Additionally, endothelial cells exhibited a highly inflammatory profile and the potential for reactive oxygen species (ROS) production. Furthermore, smooth muscle cells (SMC) showed a high propensity for extracellular matrix (ECM) deposition. Our findings broaden the current understanding of RILI and highlight potential avenues for further investigation and clinical applications.

Numerical Simulation of Proppant Transport in Major and Branching Fractures Based on CFD-DEM.

This research investigated the effect of branching fracture, proppant, and fracturing fluid on proppant transport based on the CFD-DEM coupling model. The obtained results show that the balance height of embankment in the major fracture decreases gradually with increasing angle between major and branching fractures, while it increases gradually in the branching fracture. This is because the additional resistance of fracturing fluid flow at the joint increases with increasing angle, leading to the decrease of the fracturing fluid velocity. The proppant is prone to settling in branching fractures, resulting in the increase of embankment height in the branching fracture. At angles of 45, 60, and 90°, as the diameter of the proppant increases from 0.8 to 1.1 mm, the balance height of embankment increases slightly in the major fracture, while it decreases in the branching fracture. The frictional resistance of the fracture wall enhances the difficulty of large proppant entering the branching fracture, resulting in a decrease in the amount of proppant entering the branching fracture and a decrease of the balance height of embankment in the branching fracture. In the low-viscosity fracturing fluid, the proppant quickly deposits at the bottom of the fracture as it enters the fracture. Improving the viscosity of the fracturing fluid can significantly enhance its ability to transport the proppant. The proppant is less likely to quickly settle in high-viscosity fracturing fluids, especially when the fracturing fluid viscosity exceeds 50 mPa·s.

AcousticRobots: Smart acoustically powered micro-/nanoswimmers for precise biomedical applications.

Although nanotechnology has evolutionarily progressed in biomedical field over the past decades, achieving satisfactory therapeutic effects remains difficult with limited delivery efficiency. Ultrasound could provide a deep penetration and maneuverable actuation to efficiently power micro-/nanoswimmers with little harm, offering an emerging and fascinating alternative to the active delivery platform. Recent advances in novel fabrication, controllable concepts like intelligent swarm and the integration of hybrid propulsions have promoted its function and potential for medical applications. In this review, we will summarize the mechanisms and types of ultrasonically propelled micro/nanorobots (termed here as "AcousticRobots"), including the interactions between AcousticRobots and acoustic field, practical design considerations (e.g., component, size, shape), the synthetic methods, surface modification, controllable behaviors, and the advantages when combined with other propulsion approaches. The representative biomedical applications of functional AcousticRobots are also highlighted, including drug delivery, invasive surgery, eradication on the surrounding bio-environment, cell manipulation, detection, and imaging, etc. We conclude by discussing the challenges and outlook of AcousticRobots in biomedical applications.

Ultraconformable Integrated Wireless Charging Micro-Supercapacitor Skin.

Conformable and wireless charging energy storage devices play important roles in enabling the fast development of wearable, non-contact soft electronics. However, current wireless charging power sources are still restricted by limited flexural angles and fragile connection of components, resulting in the failure expression of performance and constraining their further applications in health monitoring wearables and moveable artificial limbs. Herein, we present an ultracompatible skin-like integrated wireless charging micro-supercapacitor, which building blocks (including electrolyte, electrode and substrate) are all evaporated by liquid precursor. Owing to the infiltration and permeation of the liquid, each part of the integrated device attached firmly with each other, forming a compact and all-in-one configuration. In addition, benefitting from the controllable volume of electrode solution precursor, the electrode thickness is easily regulated varying from 11.7 to 112.5 µm. This prepared thin IWC-MSC skin can fit well with curving human body, and could be wireless charged to store electricity into high capacitive micro-supercapacitors (11.39 F cm-3) of the integrated device. We believe this work will shed light on the construction of skin-attachable electronics and irregular sensing microrobots.

Synthesis of Carboranylated Dihydropyrrolo[1,2-a]quinoxalines and Dihydroindolo[1,2-a]quinoxalines by BF3·OEt2-Catalyzed Heterocyclization of C-Formyl-o-carboranes and Investigation of Their Oxidation Stability.

A BF3·OEt2-catalyzed synthesis of carboranylated dihydropyrrolo[1,2-a]quinoxalines and dihydroindolo[1,2-a]quinoxalines in 30-99% yields is presented through the heterocyclization of various C-modified C-formyl-o-carboranes with 1-(2-aminophenyl)-pyrroles/indoles. A systematic comparative investigation of their oxidation stability in air confirmed that 4-carboranyl-4,5-dihydropyrrolo[1,2-a]quinoxaline had better stability than the 4-phenyl analogue. A cage-deboronation reaction for N-acetyl-substituted carboranylated dihydropyrrolo[1,2-a]quinoxaline produced the corresponding 7,8-nido-carborane cesium salt. A kinetic resolution was also realized to obtain an optically pure carboranylated N-heterocycle scaffold bearing a carborane cage carbon-bonded chiral stereocenter.

Ultrasound-nanovesicles interplay for theranostics.

Nanovesicles (NVs) are widely used in the treatment and diagnosis of diseases due to their excellent vascular permeability, good biocompatibility, high loading capacity, and easy functionalization. However, their yield and in vivo penetration depth limitations and their complex preparation processes still constrain their application and development. Ultrasound, as a fundamental external stimulus with deep tissue penetration, concentrated energy sources, and good safety, has been proven to be a patient-friendly and highly efficient strategy to overcome the restrictions of traditional clinical medicine. Recent research has shown that ultrasound can drive the generation of NVs, increase their yield, simplify their preparation process, and provide direct therapeutic effects and intelligent control to enhance the therapeutic effect of NVs. In addition, NVs, as excellent drug carriers, can enhance the targeting efficiency of ultrasound-based sonodynamic therapy or sonogenetic regulation and improve the accuracy of ultrasound imaging. This review provides a detailed introduction to the classification, generation, and modification strategies of NVs, emphasizing the impact of ultrasound on the formation of NVs and summarizing the enhanced treatment and diagnostic effects of NVs combined with ultrasound for various diseases.

pH/GSH dual responsive nanosystem for nitric oxide generation enhanced type I photodynamic therapy.

Tumor hypoxia diminishes the effectiveness of traditional type II photodynamic therapy (PDT) due to oxygen consumption. Type I PDT, which can operate independently of oxygen, is a viable option for treating hypoxic tumors. In this study, we have designed and synthesized JSK@PEG-IR820 NPs that are responsive to the tumor microenvironment (TME) to enhance type I PDT through glutathione (GSH) depletion. Our approach aims to expand the sources of therapeutic benefits by promoting the generation of superoxide radicals (O2-.) while minimizing their consumption. The diisopropyl group within PEG-IR820 serves a dual purpose: it functions as a pH sensor for the disassembly of the NPs to release JSK and enhances intermolecular electron transfer to IR820, facilitating efficient O2-. generation. Simultaneously, the release of JSK leads to GSH depletion, resulting in the generation of nitric oxide (NO). This, in turn, contributes to the formation of highly cytotoxic peroxynitrite (ONOO-.), thereby enhancing the therapeutic efficacy of these NPs. NIR-II fluorescence imaging guided therapy has achieved successful tumor eradication with the assistance of laser therapy.

Development and Applications of D-Amino Acid Derivatives-based Metabolic Labeling of Bacterial Peptidoglycan.

Peptidoglycan, an essential component within the cell walls of virtually all bacteria, is composed of glycan strands linked by stem peptides that contain D-amino acids. The peptidoglycan biosynthesis machinery exhibits high tolerance to various D-amino acid derivatives. D-amino acid derivatives with different functionalities can thus be specifically incorporated into and label the peptidoglycan of bacteria, but not the host mammalian cells. This metabolic labeling strategy is highly selective, highly biocompatible, and broadly applicable, which has been utilized in various fields. This review introduces the metabolic labeling strategies of peptidoglycan by using D-amino acid derivatives, including one-step and two-step strategies. In addition, we emphasize the various applications of D-amino acid derivative-based metabolic labeling, including bacterial peptidoglycan visualization (existence, biosynthesis, and dynamics, etc.), bacterial visualization (including bacterial imaging and visualization of growth and division, metabolic activity, antibiotic susceptibility, etc.), pathogenic bacteria-targeted diagnostics and treatment (positron emission tomography (PET) imaging, photodynamic therapy, photothermal therapy, gas therapy, immunotherapy, etc.), and live bacteria-based therapy. Finally, a summary of this metabolic labeling and an outlook is provided.

The functional study of a novel MKRN3 missense mutation associated with familial central precocious puberty.

Central precocious puberty (CPP) refers to a syndrome of early puberty initiation with a characteristic increase in the release of gonadotropin-releasing hormone (GnRH); therefore, it is also called GnRH-related precocious puberty. About a quarter of idiopathic central precocious puberty (ICPP) may be familial. Studies suggest that mutations of makorin ring finger protein 3 (MKRN3) can cause familial central precocious puberty (FCPP). In this report, we describe a Chinese female patient carrying a novel MKRN3 variant (c.980G>A/p.Arg327His) and presenting the CPP phenotype. This novel variant attenuated its own ubiquitination, degradation, and inhibition on the transcriptional and translational activity of GNRH1, which was verified through functional tests. We can consider this variant as a loss-of-function mutation, which subsides the inhibition of GnRH1-related signaling and gives rise to GnRH-related precocious puberty.

Enantioselective Synthesis of Biphenyl-Bridged ϵ-Sultams by Organocatalytic Mannich Reactions of Cyclic N-Sulfonylimines with Unactivated Ketones.

A highly enantioselective Mannich reaction of biphenyl-bridged seven-membered cyclic N-sulfonylimines with methyl alkyl ketones is disclosed in this study. The reaction was performed under organocatalysis by using a quinine-derived primary amine as the catalyst in combination with a Brønsted acid as the co-catalyst. High yields (up to 89 %) and excellent enantioselectivities (up to 97 % ee) were observed. For methyl alkyl ketones containing a larger alkyl substituent, specific regioselective addition to the C=N bond is favored at the methyl group. On the contrary, ketones containing a smaller alkyl substituent or hydroxyacetone substrates gave major syn selective Mannich products at the methylene group.

Building Block Metal Nanocluster-Based Growth in 1D Direction.

Metal nanoclusters with precisely modulated structures at the nanoscale give us the opportunity to synthesize and investigate 1D nanomaterials at the atomic level. Herein, it realizes selective 1D growth of building block nanocluster "Au13 Cd2 " into three structurally different nanoclusters: "hand-in-hand" (Au13 Cd2 )2 O, "head-to-head" Au25 , and "shoulder-to-shoulder" Au33 . Detailed studies further reveals the growth mechanism and the growth-related tunable properties. This work provides new hints for the predictable structural transformation of nanoclusters and atomically precise construction of 1D nanomaterials.

The Landscape of Biomimetic Nanovesicles in Brain Diseases.

Brain diseases, such as brain tumors, neurodegenerative diseases, cerebrovascular diseases, and brain injuries, are caused by various pathophysiological changes, which pose a serious health threat. Brain disorders are often difficult to treat due to the presence of the blood-brain barrier (BBB). Biomimetic nanovesicles (BNVs), including endogenous extracellular vesicles (EVs) derived from various cells and artificial nanovesicles, possess the ability to penetrate the BBB and thus can be utilized for drug delivery to the brain. BNVs, especially endogenous EVs, are widely distributed in body fluids and usually carry various disease-related signal molecules such as proteins, RNA, and DNA, and may also be analyzed to understand the etiology and pathogenesis of brain diseases. This review covers the exhaustive classification and characterization of BNVs and pathophysiological roles involved in various brain diseases, and emphatically focuses on nanotechnology-integrated BNVs for brain disease theranostics, including various diagnosis strategies and precise therapeutic regulations (e.g., immunity regulation, disordered protein clearance, anti-neuroinflammation, neuroregeneration, angiogenesis, and the gut-brain axis regulation). The remaining challenges and future perspectives regarding the nanotechnology-integrated BNVs for the diagnosis and treatment of brain diseases are also discussed and outlined.

Pd8 Nanocluster with Nonmetal-to-Metal- Ring Coordination and Promising Photothermal Conversion Efficiency.

Constructing ambient-stable, single-atom-layered metal-based materials with atomic precision and understanding their underlying stability mechanisms are challenging. Here, stable single-atom-layered nanoclusters of Pd were synthesized and precisely characterized through electrospray ionization mass spectrometry and single-crystal X-ray crystallography. A pseudo-pentalene-like Pd8 unit was found in the nanocluster, interacting with two syn PPh units through nonmetal-to-metal -ring coordination. The unexpected coordination, which is distinctly different from the typical organoring-to-metal coordination in half-sandwich-type organometallic compounds, contributes to the ambient stability of the as-obtained single-atom-layered nanocluster as revealed through theoretical and experimental analyses. Furthermore, quantum chemical calculations revealed dominant electron transition along the horizontal x-direction of the Pd8 plane, indicating high photothermal conversion efficiency (PCE) of the nanocluster, which was verified by the experimental PCE of 73.3 %. Therefore, this study unveils the birth of a novel type of compound and the finding of the unusual nonmetal-to-metal -ring coordination and has important implications for future syntheses, structures, properties, and structure-property correlations of single-atom-layered metal-based materials.