Bridging the gap:axonal fusion drives rapid functional recovery of the nervous system

Injuries to the central or peripheral nervous system frequently cause long-term disabilities because damaged neurons are unable to efficiently self-repair.This inherent deficiency necessitates the need for new treatment options aimed at restoring lost function to patients.Compared to humans,a number of species possess far greater regenerative capabilities,and can therefore provide important insights into how our own nervous systems can be repaired.In particular,several invertebrate species have been shown to rapidly initiate regeneration post-injury,allowing separated axon segments to re-join.This process,known as axonal fusion,represents a highly efficient repair mechanism as a regrowing axon needs to only bridge the site of damage and fuse with its separated counterpart in order to re-establish its original structure.Our recent findings in the nematode Caenorhabditis elegans have expanded the promise of axonal fusion by demonstrating that it can restore complete function to damaged neurons.Moreover,we revealed the importance of injury-induced changes in the composition of the axonal membrane for mediating axonal fusion,and discovered that the level of axonal fusion can be enhanced by promoting a neuron＇s intrinsic growth potential.A complete understanding of the molecular mechanisms controlling axonal fusion may permit similar approaches to be applied in a clinical setting.

Tumor recurrence after pathological complete response in locally advanced gastric cancer after neoadjuvant therapy:Two case reports

BACKGROUND The pathological complete response(ypCR)rate following neoadjuvant chemotherapy for advanced gastric cancer remains low and lacks a universally accepted treatment protocol.Immunotherapy has achieved breakthrough progress.CASE SUMMARY We report two female patients with gastric cancer defined as clinical stage cT4N1-2M0.Detection of mismatch repair protein showed mismatch repair function defect,and perioperative treatment with programmed death protein 1 inhibitor combined with S-1+oxaliplatin achieved ypCR.Surprisingly,the patients underwent clinical observation after surgery but developed different degrees of metastasis at~6 mo after surgery.CONCLUSION PD-1 inhibitor combined with chemotherapy provides a more strategic choice for comprehensive perioperative treatment of gastric cancer.

An effective pharmacological hydrogel induces optic nerve repair and improves visual function

Irreversible eye lesions, such as glaucoma and traumatic optic neuropathy, can cause blindness;however, no effective treatments exist. The optic nerve, in particular, lacks the capacity to spontaneously regenerate, requiring the development of an effective approach for optic nerve repair, which has proven challenging. Here, we demonstrate that a combination of the small molecules 3BDO and trichostatin A(TSA)—which regulate mTOR and HDAC, respectively—packaged in thermosensitive hydrogel for 4-week-sustained release after intravitreal injection, effectively induced optic nerve regeneration in a mouse model of optic nerve crush injury. Moreover, this combination of 3BDO and TSA also protected axon projections and improved visual responses in an old mouse model(11 months old) of glaucoma. Taken together, our data provide a new, local small molecule-based treatment for the effective induction of optic nerve repair, which may represent a foundation for the development of pharmacological methods to treat irreversible eye diseases.

Molecular evolutionary analysis of gene families encoding DNA recombination and repair proteins and histone demethylases,and their functional implications

Many eukaryotic genes are members of multi-gene families due to gene duplications, which generate new copies that allow functional divergence. However, the relationship between

Matrix from urine stem cells boosts tissue-specific stem cell mediated functional cartilage reconstruction

Articular cartilage has a limited capacity to self-heal once damaged.Tissue-specific stem cells are a solution for cartilage regeneration;however,ex vivo expansion resulting in cell senescence remains a challenge as a large quantity of high-quality tissue-specific stem cells are needed for cartilage regeneration.Our previous report demonstrated that decellularized extracellular matrix(dECM)deposited by human synovium-derived stem cells(SDSCs),adipose-derived stem cells(ADSCs),urine-derived stem cells(UDSCs),or dermal fibroblasts(DFs)provided an ex vivo solution to rejuvenate human SDSCs in proliferation and chondrogenic potential,particularly for dECM deposited by UDSCs.To make the cell-derived dECM(C-dECM)approach applicable clinically,in this study,we evaluated ex vivo rejuvenation of rabbit infrapatellar fat pad-derived stem cells(IPFSCs),an easily accessible alternative for SDSCs,by the abovementioned C-dECMs,in vivo application for functional cartilage repair in a rabbit osteochondral defect model,and potential cellular and molecular mechanisms underlying this rejuvenation.We found that C-dECM rejuvenation promoted rabbit IPFSCs’cartilage engineering and functional regeneration in both ex vivo and in vivo models,particularly for the dECM deposited by UDSCs,which was further confirmed by proteomics data.RNA-Seq analysis indicated that both mesenchymal-epithelial transition(MET)and inflammation-mediated macrophage activation and polarization are potentially involved in the C-dECM-mediated promotion of IPFSCs’chondrogenic capacity,which needs further investigation.

Bioadaptability:An Innovative Concept for Biomaterials

Biocompatibility is the basic requirement of biomaterials for tissue repair. However, the present concept of biocompatibility has a certain limitation in explaining the phenomena involved in biomaterial-based tissue repair. New materials, in particular those for tissue engineering and regeneration, have been developed with common characteristics, i.e. they participate deeply into important chemical and biological processes in the human body and the interaction between the biomaterials and tissues is far more complex. Understanding the interplay between these biomaterials and tissues is vital for their development and functionalization. Herein, we suggest the concept of bioadaptability of biomaterials. This concept describes the three most important aspects that can determine the performance of biomaterials in tissue repair： 1） the adaptability of the micro-environment created by biomaterials to the native microenvironment in situ; 2） the adaptability of the mechanical properties of biomaterials to the native tissue; 3） the adaptability of the degradation properties of biomaterials to the new tissue formation. The concept of bioadaptability emphasizes both the material＇s characteristics and biological aspects within a certain micro-environment and molecular mechanism. It may provide new inspiration to uncover the interaction mechanism of biomaterials and tissues, to foster the new ideas of functionalization of biomaterials and to investigate the fundamental issues during the tissue repair process by biomaterials. Furthermore, designing biomaterials with such bioadaptability would open a new door for repairing and regenerating organs or tissues. In this review, we summarized the works in recent years on the bioadaptability of biomaterials for tissue repair applications.

Pulmonary function changes following surgical correction for pectus excavatum

Objective To assess whether and to what extent pulmonary function returns to normal after surgical correction for pectus excavatum Methods Twenty seven patients who could be examined in person at the outpatient department of our hospital were included in this study Of these patients, 24 were boys and 3 were girls, with age ranging from 3 to 16 years (mean: 8 67 years) The mean age at surgery was 4 years and mean years at follow up was 6 8 Pulmonary function measurements included inspiratory vital capacity (IVC), total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC), RV/TLC ratio, maximal voluntary ventilation (MVV), forced ventilatory capacity (FVC), forced expiratory volume in one second (FEV 1), maximal mid expiratory flow (MMEF), maximal expiratory flow at 75% vital capacity (V 75 ), maximal expiratory flow at 50% vital capacity (V 50 ), maximal expiratory flow at 25% vital capacity (V 25 ) and breathing reserve ratio (BR) Results TLC, FRC, MVV, MMEF, V 75 and V 50 were not different from normal values IVC, FVC, FEV 1 and V 25 were significantly decreased compared with normal values RV and RV/TLC were high in 87 5% cases Conclusions Preoperative symptoms improved substantially after operation Little airway obstruction was observed postoperatively, suggesting that patients with pectus excavatum should have surgery as early in life as possible, preferably by age 3