The importance of fasciculation and elongation protein zeta-1 in neural circuit establishment and neurological disorders

The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly.These circuits range from short-range local signaling networks between neighboring neurons to long-range networks formed between various brain regions.Compelling converging evidence indicates that alterations in neural circuits arising from abnormalities during early neuronal development or neurodegeneration contribute significantly to the etiology of neurological disorders.Supporting this notion,efforts to identify genetic causes of these disorders have uncovered an over-representation of genes encoding proteins involved in the processes of neuronal differentiation,maturation,synaptogenesis and synaptic function.Fasciculation and elongation protein zeta-1,a Kinesin-1 adapter,has emerged as a key central player involved in many of these processes.Fasciculation and elongation protein zeta-1-dependent transport of synaptic cargoes and mitochondria is essential for neuronal development and synapse establishment.Furthermore,it acts downstream of guidance cue pathways to regulate axo-dendritic development.Significantly,perturbing its function causes abnormalities in neuronal development and synapse formation both in the brain as well as the peripheral nervous system.Mutations and deletions of the fasciculation and elongation protein zeta-1 gene are linked to neurodevelopmental disorders.Moreover,altered phosphorylation of the protein contributes to neurodegenerative disorders.Together,these findings strongly implicate the importance of fasciculation and elongation protein zeta-1 in the establishment of neuronal circuits and its maintenance.

All-in-one theranostic nanoplatfbrm with controlled drug release and activated MRI tracking functions for synergistic NIR-II hyperthermiachemotherapyof tumors

Real-time tracking drug release behavior is fundamentally important for avoiding adverse effects or unsuccessful treatment in personalizemedical treatment.However,the development of a non-invasive drug reporting platform still remains challenging.Herein the design of a novelsyn thetic magnetic resonance imaging(MRI)agent for drug release tracking(SMART)is reported,which integrates photothermal core andparamagnetic ion/drug loading shell with a thermal valve in a hybrid structure.Through near-infrared(NIR)-II photothermal effect originatingfrom inner Au-Cu9S5 nanohybrid core,burst release of drugs loaded in the mesoporous silica shell is achieved.The concomitant use of aphase change material not only prevents premature drug release,but also regulates heating effect,keeping local temperature below 45℃,enabling synergistic chemotherapy and mild hyperthermia in vitro and in vivo.Furthermore,the drug release from SMART facilitates protonaccessibility to the paramagnetic ions anchored inside mesopores channels,enhancing Iongitudinal T1 relaxation rate and displaying positivesignal correlation to the amount of released drug,thus allowing norvinvasive real-time monitoring of drug release event.The current studyhighlights the potential of designed MRI nanophores such as SMART for real-time and in-situ monitoring of drug delivery for precisionthera nostic applications.

Modular micro-PCR system for the onsite rapid diagnosis of COVID-19

Effective containment of the COVID-19 pandemic requires rapid and accurate detection of the pathogen.Polymerase chain reaction(PCR)remains the gold standard for COVID-19 confirmation.In this article,we report the performance of a cost-effective modular microfluidic reverse transcription(RT)-PCR and RT-loop mediated isothermal amplification(RTLAMP)platform,Epidax®,for the point-of-care testing and confirmation of SARS-CoV-2.This platform is versatile and can be reconfigured either for screening using endpoint RT-PCR or RT-LAMP tests or for confirmatory tests using realtime RT-PCR.Epidax®is highly sensitive and detects as little as 1 RNA copy perµL for real-time and endpoint RT-PCR,while using only half of the reagents.We achieved comparable results with those of a commercial platform when detecting SARS-CoV-2 viruses from 81 clinical RNA extracts.Epidax®can also detect SARS-CoV-2 from 44 nasopharyngeal samples without RNA extraction by using a direct RT-PCR assay,which shortens the sample-to-answer time to an hour with minimal user steps.Furthermore,we validated the technology using an RT-LAMP assay on 54 clinical RNA extracts.Overall,our platform provides a sensitive,cost-effective,and accurate diagnostic solution for lowresource settings.

Matrisomal genes in squamous cell carcinoma of head and neck influence tumor cell motility and response to cetuximab treatment

Dear Editor,Head and neck squamous cell carcinoma(HNSCC)is the sixth most common cancer globally[1,2].Despite the improvement in treatment modalities,up to 50%of HNSCC patients still develop recurrent/metastatic(R/M)disease[3],and platinum-based chemotherapy with cetuximab and/or pembrolizumab has become the standard of care[4].However,R/M HNSCC is challenging to treat,the prognosis is poor,and there is an unmet need for new therapeutic targets.