SARS-CoV-2 getting into the brain;neurological phenotype of COVID-19,and management by nano-biotechnology

Human coronavirus infection getting into the brain:By February 2022,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,causing the coronavirus disease 2019(COVID-19)outbreak,has infected around 415 million people,and caused~5.8 million deaths worldwide(WHO,https://covid19.who.int/).As SARS-CoV-2 replicates during the infection,it undergoes genetic mutation to generate variants with varying characteristics and mutation frequencies.The emerging,over time,new variants that differ with transmissibility,immunity,and infection severity pose continuous challenges to established COVID-19 management strategies and regulations.Several SARS-CoV-2 variants such as Omicron(B.1.1.529),Delta(B.1.617.2),UK(B.1.17),South Africa(B.1.351),Brazil(P.1),and New York B.1.525-B.1.526 were detected worldwide and accelerated severity of COVID-19 pandemic(Figure 1A;McQuaid et al.,2021).

MXene‑Graphene Composites:A Perspective on Biomedical Potentials

MXenes,transition metal carbides and nitrides with graphene-like structures,have received considerable attention since their first discovery.On the other hand,Graphene has been extensively used in biomedical and medicinal applications.MXene and graphene,both as promising candidates of two-dimensional materials,have shown to possess high potential in future biomedical applications due to their unique physicochemical properties such as superior electrical conductivity,high biocompatibility,large surface area,optical and magnetic features,and extraordinary thermal and mechanical properties.These special structural,functional,and biological characteristics suggest that the hybrid/composite structure of MXene and graphene would be able to meet many unmet needs in different fields;particularly in medicine and biomedical engineering,where high-performance mechanical,electrical,thermal,magnetic,and optical requirements are necessary.However,the hybridization and surface functionalization should be further explored to obtain biocompatible composites/platforms with unique physicochemical properties,high stability,and multifunctionality.In addition,toxicological and long-term biosafety assessments and clinical translation evaluations should be given high priority in research.Although very limited studies have revealed the excellent potentials of MXene/graphene in biomedicine,the next steps should be toward the extensive research and detailed analysis in optimizing the properties and improving their functionality with a clinical and industrial outlook.Herein,different synthesis/fabrication methods and performances of MXene/graphene composites are discussed for potential biomedical applications.The potential toxicological effects of these composites on human cells and tissues are also covered,and future perspectives toward more successful translational applications are presented.The current state-of-the-art biotechnological advances in the use of MXene-Graphene composites,as well as their developmental challenges and future prospects are also deliberated.Due to the superior properties and multifunctionality of MXene-graphene composites,these hybrid structures can open up considerable new horizons in future of healthcare and medicine.

Size matters:the biochemical logic of ligand type in endocrine crosstalk

The endocrine system is a fundamental type of long-range cell-cell communication that is important for maintaining metabolism,physiology,and other aspects of organismal homeostasis.Endocrine signaling is mediated by diverse blood-borne ligands,also called hormones,including metabolites,lipids,steroids,peptides,and proteins.The size and structure of these hormones are fine-tuned to make them bioactive,responsive,and adaptable to meet the demands of changing environments.Why has nature selected such diverse ligand types to mediate communication in the endocrine system?What is the chemical,signaling,or physiologic logic of these ligands?What fundamental principles from our knowledge of endocrine communication can be applied as we continue as a field to uncover additional new circulating molecules that are claimed to mediate long-range cell and tissue crosstalk?This review provides a framework based on the biochemical logic behind this crosstalk with respect to their chemistry,temporal regulation in physiology,specificity,signaling actions,and evolutionary development.

A Novel Vision of Reinforcing Nanofibrous Masks with Metal Nanoparticles:Antiviral Mechanisms Investigation

Prevention of spreading viral respiratory disease,especially in case of a pandemic such as coronavirus disease of 2019(COVID-19),has been proved impossible without considering obligatory face mask-wearing protocols for both healthy and contaminated populations.The widespread application of face masks for long hours and almost everywhere increases the risks of bacterial growth in the warm and humid environment inside the mask.On the other hand,in the absence of antiviral agents on the surface of the mask,the virus may have a chance to stay alive and be carried to different places or even put the wearers at risk of contamination when touching or disposing the masks.In this article,the antiviral activity and mechanism of action of some of the potent metal and metal oxide nanoparticles in the role of promising virucidal agents have been reviewed,and incorporation of them in an electrospun nanofibrous structure has been considered an applicable method for the fabrication of innovative respiratory protecting materials with upgraded safety levels.

Accurate nanoelectrode recording of human pluripotent stem cell-derived cardiomyocytes for assaying drugs and modeling disease

The measurement of the electrophysiology of human pluripotent stem cell-derived cardiomyocytes is critical for their biomedical applications,from disease modeling to drug screening.Yet,a method that enables the high-throughput intracellular electrophysiology measurement of single cardiomyocytes in adherent culture is not available.To address this area,we have fabricated vertical nanopillar electrodes that can record intracellular action potentials from up to 60 single beating cardiomyocytes.Intracellular access is achieved by highly localized electroporation,which allows for low impedance electrical access to the intracellular voltage.Herein,we demonstrate that this method provides the accurate measurement of the shape and duration of intracellular action potentials,validated by patch clamp,and can facilitate cellular drug screening and disease modeling using human pluripotent stem cells.This study validates the use of nanopillar electrodes for myriad further applications of human pluripotent stem cell-derived cardiomyocytes such as cardiomyocyte maturation monitoring and electrophysiology-contractile force correlation.

Cell Stem Cell：利用干细胞制造出的心肌细胞有助精准心血管医疗取得进展

在一项新的研究中。来自美国斯坦福大学医学院的研究人员发现利用人诱导性多能干细胞（iPS细胞）制造的心肌细胞忠实地反映供者天然的心脏组织中关键基因的表达模式。因此，这些细胞能够被用来预测病人是否可能经历药物相关的心脏损伤。相关研究结果在线发表在Cell Stem Cell期刊上。论文标题为＂Transcriptome Profiling of Patient -Specific Human iPSC - ardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro＂.

To manage long COVID by selective SARS-CoV-2 infection biosensing

According to the National Institutes of Health(NIH),the initiative of The Rapid Acceleration of Diagnostics Tech and Advanced Technology Platforms(RADxTech/ATP)program was established to promote research and development(R&D)in the field of investigating selective,sensitive,and affordable sensing technologies for coronavirus disease 2019(COVID-19)diagnostics.This is a goaloriented approach toward point-of-care testing(POCT)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection management applications.Till May 2022,RADxTech/ATP has been involved in 1.9 billion tests production,44 FDA authorized tests,first over-the-counter test for POCT and home-based testing,and>100 companies dedicated to smart sensor development(https://www.nibib.nih.gov/covid-19/radx-tech-program/radx-tech-dashboard).Despite such outstanding growth,COVID-19 management is far from in control due to SARS-CoV-2 mutations,virus presence in life systems(including human-to-human transmission,water,food,animal,and air[mainly indoor premises])。

Differential Responses of Transplanted Stem Cells to Diseased Environment Unveiled by a Molecular NIR-II Cell Tracker

Stem cell therapy holds high promises in regenerative medicine.The major challenge of clinical translation is to precisely and quantitatively evaluate the in vivo cell distribution,migration,and engraftment,which cannot be easily achieved by current techniques.To address this issue,for the first time,we have developed a molecular cell tracker with a strong fluorescence signal in the second near-infrared(NIR-II)window(1,000-1,700 nm)for real-time monitoring of in vivo cell behaviors in both healthy and diseased animal models.The NIR-II tracker(CelTrac1000)has shown complete cell labeling with low cytotoxicity and profound long-term tracking ability for 30 days in high spatiotemporal resolution for semiquantification of the biodistribution of transplanted stem cells.Taking advantage of the unique merits of CelTrac1000,the responses of transplanted stem cells to different diseased environments have been discriminated and unveiled.Furthermore,we also demonstrate CelTrac1000 as a universal and effective technique for ultrafast real-time tracking of the cellular migration and distribution in a 100μm single-cell cluster spatial resolution,along with the lung contraction and heart beating.As such,this NIR-II tracker will shift the optical cell tracking into a single-cell cluster and millisecond temporal resolution for better evaluating and understanding stem cell therapy,affording optimal doses and efficacy.

Macrophage-targeted single walled carbon nanotubes stimulate phagocytosis via pH-dependent drug release

Atherosclerotic cardiovascular disease is the leading cause of mortality in the world.A driving feature of atherosclerotic plaque formation is dysfunctional efferocytosis.Because the“don’t eat me”molecule CD47 is upregulated in atherosclerotic plaque cores,CD47-blocking strategies can stimulate the efferocytic clearance of apoptotic cells and thereby help prevent the progression of plaque buildup.However,these therapies are generally costly and,in clinical and murine trials,they have resulted in side effects including anemia and reticulocytosis.Here,we developed and characterized an intracellular phagocytosis-stimulating treatment in the CD47-SIRPαpathway.We loaded a novel monocyte/macrophage-selective nanoparticle carrier system with a small molecule enzymatic inhibitor that is released in a pH-dependent manner to stimulate macrophage efferocytosis of apoptotic cell debris via the CD47-SIRPαsignaling pathway.We demonstrated that single-walled carbon nanotubes(SWNTs)can selectively deliver tyrosine phosphatase inhibitor 1(TPI)intracellularly to macrophages,which potently stimulates efferocytosis,and chemically characterized the nanocarrier.Thus,SWNT-delivered TPI can stimulate macrophage efferocytosis,with the potential to reduce or prevent atherosclerotic disease.

An extracellular matrix paradox in myocardial scar formation

In a recent article in Cell,Yokota et al.1 demonstrate that type V collagen,a minor component of the cardiac extracellular matrix,plays a paradoxical role in limiting scar size after myocardial infarction by altering the mechanical properties of the developing scar tissue and by regulating integrindependent activation of cardiac fibroblasts(Fig.1).