Boosting mRNA-Engineered Monocytes via Prodrug-Like Microspheres for Bone Microenvironment Multi-Phase Remodeling.

Monocytes, as progenitors of macrophages and osteoclasts, play critical roles in various stages of bone repair, necessitating phase-specific regulatory mechanisms. Here, icariin (ICA) prodrug-like microspheres (ICA@GM) are developed, as lipid nanoparticle (LNP) transfection boosters, to construct mRNA-engineered monocytes for remodeling the bone microenvironment across multiple stages, including the acute inflammatory and repair phases. Initially, ICA@GM is prepared from ICA-conjugated gelatin methacryloyl via a microfluidics system.

Targeting Osteoblast-Osteoclast Cross-Talk Bone Homeostasis Repair Microcarriers Promotes Intervertebral Fusion in Osteoporotic Rats.

Balancing osteoblast-osteoclast (OB-OC) cross-talk is crucial for restoring bone tissue structure and function. Current clinical drugs targeting either osteogenesis or osteoclastogenesis fail to effectively regulate cross-talk, impeding efficient bone repair in osteoporosis patients. Ubiquitin-specific protease 26 (USP26) is shown to coordinate OB-OC cross-talk by independently regulating β-catenin and Iκb-α.

HIF-1α protects nucleus pulposus cells from oxidative stress-induced mitochondrial impairment through PDK-1.

The pathogenesis of intervertebral disc degeneration (IVDD) involves complex signaling networks and various effector molecules, and our understanding of the pathogenesis of IVDD is limited. Hypoxia inducible factor-1α (HIF-1α) is closely related to IVDD, and there is excessive oxidative stress concurrent with IVDD. In this study, we found that HIF-1α could protect nucleus pulposus cells from excessive oxidative stress by reversing the imbalance between oxidants and antioxidants and thus mitigating the oxidative stress-induced mitochondrial impairment.

IR-780 Dye-based Targeting of Cancer-associated Fibroblasts Improves Cancer Immunotherapy by Increasing Intra-tumoral T Lymphocytes Infiltration.

Background: Immune-checkpoint inhibitors (ICIs) against programmed death (PD)-1/PD-L1 pathway immunotherapy have been demonstrated to be effective in only a subset of patients with cancer, while the rest may exhibit low response or may develop drug resistance after initially responding. Previous studies have indicated that extensive collagen-rich stroma secreted by cancer-associated fibroblasts (CAFs) within the tumor microenvironment is one of the key obstructions of the immunotherapy for some tumors by decreasing the infiltrating cytotoxic T cells. However, there is still a lack of effective therapeutic strategies to control the extracellular matrix by targeting CAFs.

Targeted Protein Fate Modulating Functional Microunits Promotes Intervertebral Fusion.

Stable regulation of protein fate is a prerequisite for successful bone tissue repair. As a ubiquitin-specific protease (USP), USP26 can stabilize the protein fate of β-catenin to promote the osteogenic activity of mesenchymal cells (BMSCs) and significantly increased bone regeneration in bone defects in aged mice. However, direct transfection of Usp26 in vivo is inefficient.

Temporal soliton dynamics of synchronised ultrafast fibre lasers.

Synchronised ultrafast soliton lasers have attracted great research interest in recent decades. However, there is a lack of comprehensive understanding regarding the buildup mechanism of synchronised pulses. Here, we report a dynamic analysis of independent and synchronised solitons buildup mechanisms in synchronised ultrafast soliton lasers.

Broadband synchronization of ultrafast pulse generation with double-walled carbon nanotubes.

Double-walled carbon nanotubes have shown competitive properties in broadband optical pulse generation owning to the intrinsic electronic properties. Synchronization of ultrafast optical pulses in multiple wavelengths is a key technique for numerous applications, such as nonlinear frequency conversion, ultrafast pump-probe, coherent Raman scattering spectroscopy, coherent optical synthesis, etc. In this work, we demonstrate the mode-locking and synchronization of 1.

Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium.

Background: Radiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation. The most important feature of radiation ulcers is progressive ulceration, which results in the expansion of radiation injury to the nonirradiated area and refractory wounds. Current theories cannot explain the progression of radiation ulcers.

Synchronized triple-wavelength fiber lasers at 1, 1.55, and 1.9 µm.

Synchronized lasers working at different wavelengths are of great significance for numerous applications, such as high-energy femtosecond pulse emission, Raman microscopy, and precise timing distribution. Here, we report synchronized triple-wavelength fiber lasers working at 1, 1.55, and 1.

A small-molecule inhibitor of Keap1-Nrf2 interaction attenuates sepsis by selectively augmenting the antibacterial defence of macrophages at infection sites.

Background: Macrophages at infection sites are considered as the promising therapeutic targets to prevent sepsis development. The Nrf2/Keap1 system acts as a critical modulator of the antibacterial activity of macrophages. Recently, Keap1-Nrf2 protein-protein interaction (PPI) inhibitors have emerged as safer and stronger Nrf2 activators; however, their therapeutic potential in sepsis remains unclear.

Mitochondrial-targeting fluorescent small molecule IR-780 alleviates radiation-induced brain injury.

Radiation-induced brain injury (RIBI) is a common complication of radiation therapy for brain tumors. Vascular damage is one of the key factors closely related to the severity of the RIBI. However, effective vascular target treatment strategies are lacking.

Near-infrared Nrf2 activator IR-61 dye alleviates radiation-induced lung injury.

Oxidative stress injury and subsequent inflammatory response are considered to play critical roles in radiation-induced lung injury (RILI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates oxidative stress response and represses inflammation, but its therapeutic value in RILI remains elusive. Our previous studies have shown that the near-infrared (NIR) IR-61 dye evokes intracellular antioxidant defense by enhancing Nrf2 signaling and promoting anti-inflammatory effects.

Intervertebral Disc Degeneration and Low Back Pain Depends on Duration and Magnitude of Axial Compression.

Purpose: The pathological role of axial stress in intervertebral disc degeneration (IDD) is controversial, and there was no quantified study until now. Here, we tried to clarify the correlation between IDD or low back pain (LBP) and axial stress at different duration and magnitude in vitro and in vivo.

Method: In vitro, the gene expression of aggrecan, matrix metalloproteinase-3 (MMP3), calcitonin gene-related peptide (CGRP), and substance P (SP) was measured when nucleus pulposus cells (NPCs) were compressed under gradual severity.

Propionibacterium acnes contributes to low back pain via upregulation of NGF in TLR2-NF-κB/JNK or ROS pathway.

Propionibacterium acnes infection in intervertebral discs (IVDs) is a newly identified cause of low back pain (LBP). In the present study, we aimed to determine whether the nerve growth factor (NGF), a critical pro-algesic factor, is involved in P. acnes-induced LBP.

G-Protein Coupled Receptor 35 Induces Intervertebral Disc Degeneration by Mediating the Influx of Calcium Ions and Upregulating Reactive Oxygen Species.

Intervertebral disc degeneration (IDD) is a chronic disease affecting millions of patients; however, its specific etiology is unknown. G protein-coupled receptors (GPRs) are a superfamily of integral membrane receptors in cells, and the receptors respond to a diverse range of stimuli and participate in multiple cellular activities. Here, using RNA-sequencing (RNA-seq) methods and immunohistochemistry, we revealed that G protein-coupled receptor 35 (GPR35) may have a relationship with IDD.

Increased Expression of Integrin Alpha 6 in Nucleus Pulposus Cells in Response to High Oxygen Tension Protects against Intervertebral Disc Degeneration.

The destruction of the low oxygen microenvironment in nucleus pulposus (NP) cells played a critical role in the pathogenesis of intervertebral disc degeneration (IVDD). The purpose of this study was to determine the potential role of integrin alpha 6 (ITG 6) in NP cells in response to high oxygen tension (HOT) in IVDD. Immunofluorescence staining and western blot analysis showed that the levels of ITG 6 expression were increased in the NP tissue from IVDD patients and the IVDD rat model with mild degeneration, which were reduced as the degree of degeneration increases in severity.

Pharmaceutical targeting of succinate dehydrogenase in fibroblasts controls bleomycin-induced lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix in the lung with fibroblast-to-myofibroblast transition, leading to chronically compromising lung function and death. However, very little is known about the metabolic alterations of fibroblasts in IPF, and there is still a lack of pharmaceutical agents to target the metabolic dysregulation. Here we show a glycolysis upregulation and fatty acid oxidation (FAO) downregulation in fibroblasts from fibrotic lung, and perturbation of glycolysis and FAO affects fibroblasts transdifferentiation.

Reactive Oxygen Species Mediate Low Back Pain by Upregulating Substance P in Intervertebral Disc Degeneration.

Reactive oxygen species (ROS) are thought to have a strong correlation with a number of intervertebral disc (IVD) diseases. Here, we aimed to determine whether ROS represent an etiology of low back pain (LBP) during IVD degeneration. Thirty degenerated intervertebral disc samples were obtained from patients, and ROS levels were quantified using dihydroethidium (DHE) staining.

TRIM21 drives intervertebral disc degeneration induced by oxidative stress via mediating HIF-1α degradation.

The onset and progression of intervertebral disc degeneration (IVDD) is strictly associated with oxidative stress. TRIM21 (Tripartite motif-containing protein 21), a ubiquitin E3 ligase, has been shown to play an essential role in liver redox homeostasis; however, whether TRIM21 is involved in IVDD, especially in oxidative stress-induced IVDD, is unknown. Here, we reported that TRIM21 was upregulated in nucleus pulposus (NPs) with increasing severity of IVDD, and that oxidative stress was a stimulator of TRIM21 expression.

Knockdown of PC4 increases chemosensitivity of Oxaliplatin in triple negative breast cancer by suppressing mTOR pathway.

As a multifunctional nuclear protein, the human positive cofactor 4 (PC4) is highly expressed in various tumors including breast cancer and has potential roles in cancer development and progression. However, the functional signatures and molecular mechanisms of PC4 in triple negative breast cancer (TNBC) progression and chemotherapeutic response are still unknown. In this study, we found that PC4 is significantly upregulated in TNBC cells compared with non-TNBC cells, implying its potential role in TNBC.

Mitigation of radiation-induced pulmonary fibrosis by small-molecule dye IR-780.

Radiation-induced pulmonary fibrosis (RIPF) is a common complication during thoracic radiotherapy, but there are few effective treatments. Here, we identify IR-780, a mitochondria-targeted near-infrared (NIR) dye, can selectively accumulate in the irradiated lung tissues. Besides, IR-780 significantly alleviates radiation-induced acute lung injury and fibrosis.

A novel in vivo mouse intervertebral disc degeneration model induced by compressive suture.

Intervertebral disc degeneration (IDD) is the root cause of many musculoskeletal disorders of the spine. However, the etiology of IDD is complex and still not well understood. Animal models of IDD would be useful in deciphering the underlying mechanisms.

Bi-needle technique versus transforaminal endoscopic spine system technique for percutaneous endoscopic lumbar discectomy in treating intervertebral disc calcification: a propensity score matched cohort analysis.

Objective: The aim of this study was to evaluate the clinical results of a Bi-needle technique and conventional transforaminal endoscopic spine system (TESSYS) technique for percutaneous endoscopic lumbar discectomy (PELD) in treating patients with intervertebral disc calcification (IDC).

Background: PELD has gained acceptance for treating patients with IDC. The Bi-needle technique was designed to improve the efficiency and safety of PELD.

Anthropogenic Perchlorate Increases since 1980 in the Canadian High Arctic.

An ice core of 15.5 m retrieved from Agassiz Ice Cap (Nunavut, Canada) in April 2009 was analyzed for perchlorate to obtain a temporal trend in the recent decades and to better understand the factors affecting High Arctic deposition. The continuous record dated from 1936 to 2007, covers the periods prior to and during the major atmospheric releases of organic chlorine species that affected the stratospheric ozone levels.