Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants(SCVs).Moreover,microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process,leading to impaired bone defect repair.Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade,challenges remain in clinical management.The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections,but a comprehensive review of their research progress is lacking.This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration,and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Brain Pathology in COVID-19:Clinical Manifestations and Potential Mechanisms

Neurological manifestations of coronavirus disease 2019(COVID-19)are less noticeable than the respiratory symptoms,but they may be associated with disability and mortality in COVID-19.Even though Omicron caused less severe disease than Delta,the incidence of neurological manifestations is similar.More than 30%of patients experienced“brain fog”,delirium,stroke,and cognitive impairment,and over half of these patients presented abnormal neuroimaging outcomes.In this review,we summarize current advances in the clinical findings of neurological manifestations in COVID-19 patients and compare them with those in patients with influenza infection.We also illustrate the structure and cellular invasion mechanisms of SARS-CoV-2 and describe the pathway for central SARS-CoV-2 invasion.In addition,we discuss direct damage and other pathological conditions caused by SARS-CoV-2,such as an aberrant interferon response,cytokine storm,lymphopenia,and hypercoagulation,to provide treatment ideas.This review may offer new insights into preventing or treating brain damage in COVID-19.

Adding Fuel to the Fire by Increased GABAergic Inhibition:A Seizure-Amplifying Nigra-Parafascicular Pathway

Epilepsy is a common neurological disorder characterized by recurrent seizures.Most anti epileptic drugs (AEDs)work by regulating the balance of the excitatory glutamatergic and inhibitory GABAergic transmission.However,the current AEDs cannot successfully control seizures in most (>70%) patients with temporal lobe epilepsy (TLE)[1],in whom seizures typically begin in the hippocampus.This may be caused by changes in the synaptic efficacy and remodeling of neural circuits,such as alterations in the distribution/expression of GABA_A receptor subunits and mossy-fiber sprouting.Since Dr.Karen Gale and colleagues originally described the seizure-modulating effects of nigral GABAergic transmission in the early 1980s [2]。