An ingenious design from nature to accelerate the repair of long-bone critical defects: the longitudinal tubular transverse interconnection structure of deer antlers.

Deer antlers, the only mammalian bony organs capable of complete regeneration, exhibit a growth rate of 2.7 cm/day, far surpassing human long bones (1 mm/day). Long-bone critical defects (LBCDs) occur when defects exceed intrinsic healing capacity.

A predictive endocrine resistance index accurately stratifies luminal breast cancer treatment responders and non-responders.

Background: Endocrine therapy (ET) with tamoxifen (TAM) or aromatase inhibitors (AI) is highly effective against hormone receptor (HR) positive early breast cancer (BC), but resistance remains a major challenge. The primary objectives of our study were to understand the underlying mechanisms of primary resistance and to identify potential biomarkers.

Methods: We selected >800 patients in three sub-cohorts (Discovery, N=364, matched pairs), Validation 1, N=270, Validation 2, N= 176) of the West German Study Group (WSG) Adjuvant Dynamic marker-Adjusted Personalized Therapy (ADAPT) trial who underwent short-term pre-operative TAM or AI treatment.

Augmenting osteoporotic osseointegration through a temporal release nanocoating-based reversing dysregulated osteogenic microenvironment.

Rationale: Imbalances in the osteogenic-osteoclastic microenvironment hinder effective osseointegration between the prosthesis and host bone, which is a key factor contributing to the high incidence of prosthesis loosening and periprosthetic fractures in osteoporosis patients. Developing an implant interface that can reverse the dysregulated osteogenic microenvironment is an effective strategy to address this challenge.

Methods: A novel bioinspired interface with a spatial gradient structure was engineered by 3D-printed porous titanium alloy implants and hollow mesoporous silica nanoparticles coating.

Antlers on does: An unexpected role of macrophages in deer biology.

Antlers, a male deer secondary sex characteristic, are unique mammalian appendages that fully regenerate annually, under androgen regulation. Stem cells located in the antlerogenic periosteum (AP), a tissue overlaying the frontal crest of both male and female deer, play a crucial role in antlerogenesis. Nonetheless, the underlying molecular mechanisms as to how antlerogenesis is regulated by androgens remain largely unexplored.

BRCA1 is involved in sustaining rapid antler growth possibly via balancing of the p53/endoplasmic reticulum stress signaling pathway.

Background: Regeneration is the preferred approach to restore the structure and function after tissue damage. Rapid proliferation of cells over the site of damage is integral to the process of regeneration. However, even subtle mutations in proliferating cells may cause detrimental effects by eliciting abnormal differentiation.

Systemic factors associated with antler growth promote complete wound healing.

Deer antlers are the only mammalian appendages that can fully regenerate from periosteum of pedicles (PP). This regeneration process starts from regenerative healing of wounds. Removal of PP abolishes antler regeneration, however, the regenerative cutaneous wound healing proceeds, indicating that some factors in the circulation contribute to this healing.

Bone metabolism associated with annual antler regeneration: a deer insight into osteoporosis reversal.

Osteoporosis, a metabolic disorder, remains challenging to treat due to limited understanding of its underlying mechanism. The annual cycle of "cyclic physiological osteoporosis (CPO)" and its full reversal in male deer represents a unique natural model for studying this condition. Deer antlers, weighing up to 25 kg/pair, derive over 60% of their mineral contents from deer skeleton during mineralization.

Neurophysiological features of STN LFP underlying sleep fragmentation in Parkinson's disease.

Background: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear.

Method: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication.

Reciprocal negative feedback between Prrx1 and miR-140-3p regulates rapid chondrogenesis in the regenerating antler.

During growth phase, antlers exhibit a very rapid rate of chondrogenesis. The antler is formed from its growth center reserve mesenchyme (RM) cells, which have been found to be the derivatives of paired related homeobox 1 (Prrx1)-positive periosteal cells. However, the underlying mechanism that drives rapid chondrogenesis is not known.

Conditioned Media from Deer Antler Stem Cells Effectively Alleviate Type 1 Diabetes Mellitus Possibly via Inhibiting the NF-κB Signaling Pathway.

Background: Type 1 diabetes mellitus (T1D) represents a severe threat to human health. Persistent hyperglycemia and dyslipidemia can lead to damaged liver function, while effective interventions for these complications are currently lacking. Deer antler stem cells (AnSCs), a novel type of adult stem cells, significantly reduced liver injury, which was speculated to be achieved through the paracrine pathway.

The intestinal epithelial-macrophage-crypt stem cell axis plays a crucial role in regulating and maintaining intestinal homeostasis.

The intestinal tract plays a vital role in both digestion and immunity, making its equilibrium crucial for overall health. This equilibrium relies on the dynamic interplay among intestinal epithelial cells, macrophages, and crypt stem cells. Intestinal epithelial cells play a pivotal role in protecting and regulating the gut.

Antler thymosin β10 reduces liver fibrosis via inhibiting TGF-β1/SMAD pathway.

Hepatic stellate cell (HSC) activation is a crucial step in the development of liver fibrosis. Previous studies have shown that antler stem cells (AnSCs) inhibited HSC activation, suggesting that this may be achieved through secreting or releasing peptides. This study aimed to investigate whether AnSC-derived peptides (AnSC-P) could reduce liver fibrosis.

SiRNF8 Delivered by DNA Framework Nucleic Acid Effectively Sensitizes Chemotherapy in Colon Cancer.

Background: The evident side effects and decreased drug sensitivity significantly restrict the use of chemotherapy. However, nanoparticles based on biomaterials are anticipated to address this challenge.

Methods: Through bioinformatics analysis and colon cancer samples, we initially investigated the expression level of RNF8 in colon cancer.

Transarterial chemoembolization combined donafenib with/without PD-1 for unresectable HCC in a multicenter retrospective study.

Background & Aims: This multicenter retrospective study evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with donafenib and a programmed death-1 (PD-1) inhibitor (TACE+DP) and TACE combined with donafenib (TACE+D) for unresectable hepatocellular carcinoma (uHCC).

Methods: The clinical data of 388 patients with uHCC who received TACE+DP or TACE+D as first-line treatment at six Chinese academic centers from July 2021 to July 2022 were collected and analyzed retrospectively. Patients in the TACE+DP group received an intravenous administration of a PD-1 inhibitor every three weeks and oral donafenib (0.

Antler stem cell-derived exosomes promote regenerative wound healing via fibroblast-to-myofibroblast transition inhibition.

Introduction: The typical outcome of mammalian wound healing is scarring, a fibrotic process mediated by myofibroblast aggregation. Perfect healing in a clinical setting is relatively unexplored. Surprisingly, our previous studies have shown that the large wound (10 cm diameter or more) of the pedicle of deer naturally achieves regenerative restoration, realized through a paracrine pathway from adjacent antler stem cells (AnSCs).

Antler stem cell exosomes alleviate pulmonary fibrosis via inhibiting recruitment of monocyte macrophage, rather than polarization of M2 macrophages in mice.

Pulmonary fibrosis (PF), a chronic interstitial lung disease, is characterized by over-abundant deposition of extracellular matrix consisting mainly of collagen I. In previous studies, we demonstrated that deer antler stem cells (AnSCs), a novel type of adult stem cell, are capable of significantly down-regulating collagen formation in different organs and tissues and speculated that they could effectively treat PF via reducing collagen deposition in the lung tissue. In the present study, we found that administration of AnSCs improved the survival rate of PF mice and reduced lung fibrosis, collagen deposition and myofibroblast differentiation.

Protein crotonylation: An emerging regulator in DNA damage response.

DNA damage caused by internal or external factors lead to increased genomic instability and various diseases. The DNA damage response (DDR) is a crucial mechanism that maintaining genomic stability through detecting and repairing DNA damage timely. Post-translational modifications (PTMs) play significant roles in regulation of DDR.

Injectable hydrogel made from antler mesenchyme matrix for regenerative wound healing creating a fetal-like niche.

Background: Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing. Previous studies have indicated that antler reserve mesenchyme (RM) cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages.

Aim: To develop hydrogels from the antler RM matrix (HARM) and evaluate the effect on wound healing.

Macrophage-Related Testicular Inflammation in Individuals with Idiopathic Non-Obstructive Azoospermia: A Single-Cell Analysis.

Male infertility is a global issue that seriously affects reproductive health. This study aimed to understand the underlying causes of idiopathic non-obstructive azoospermia (iNOA), which is a type of male infertility with unknown origins that accounts for 10-15% of cases. By using single-cell analysis techniques, we aimed to uncover the mechanisms of iNOA and gain insight into the cellular and molecular changes in the testicular environment.

A population of stem cells with strong regenerative potential discovered in deer antlers.

The annual regrowth of deer antlers provides a valuable model for studying organ regeneration in mammals. We describe a single-cell atlas of antler regrowth. The earliest-stage antler initiators were mesenchymal cells that express the paired related homeobox 1 gene ( mesenchymal cells).

Placental stem cells-derived exosomes stimulate cutaneous wound regeneration engrailed-1 inhibition.

Skin wounds generally heal by scarring, a fibrotic process mediated by the Engrailed-1 (EN1) fibroblast lineage. Scar is detrimental to tissue structure and function, but perfect healing in clinical settings remains to be explored. Recent studies have shown that mesenchymal stem cell (MSC) transplantation can reduce scarring Here, we investigated the effects of placental MSCs (pMSCs) and exosomes derived from pMSCs (pMSC-exos) on wound healing using a full-thickness rat model.

Single-cell transcriptome reveals core cell populations and androgen-RXFP2 axis involved in deer antler full regeneration.

Deer antlers constitute a unique mammalian model for the study of both organ formation in postnatal life and annual full regeneration. Previous studies revealed that these events are achieved through the proliferation and differentiation of antlerogenic periosteum (AP) cells and pedicle periosteum (PP) cells, respectively. As the cells resident in the AP and the PP possess stem cell attributes, both antler generation and regeneration are stem cell-based processes.