Application of super-resolution fluorescence microscopy in hematologic malignancies

Hematologic malignancies are one of the most common malignant tumors caused by the clonal proliferation and differentiation of hematopoietic and lymphoid stem cells.The examination of bone marrow cells combined with immunodeficiency typing is of great significance to the diagnostic type,treatment and prognosis of hematologic malignancies.Super-resolution fluorescence microscopy(SRM)is a special kind of optical microscopy technology,which breaks the resolution limit and was awarded the Nobel Prize in Chemistry in 2014.With the development of SRM,many related technologies have been applied to the diagnosis and treatment of clinical diseases.It was reported that a major type of SRM technique,single molecule localization microscopy(SMLM),is more sensitive than flow cytometry(FC)in detecting cell membrane antigens'expression,thus enabling better chances in detecting antigens on hematopoietic cells than traditional analytic tools.Furthermore,SRM may be applied to clinical pathology and may guide precision medicine and personalized medicine for clone hematopoietic cell diseases.In this paper,we mainly discuss the application of SRM in clone hematological malignancies.

Glycodiversification of gentamicins through in vivo glycosyltransferase swapping enabled the creation of novel hybrid aminoglycoside antibiotics with potent activity and low ototoxicity

Aminoglycosides(AGs)are a class of antibiotics with a broad spectrum of activity.However,their use is limited by safety concerns associated with nephrotoxicity and ototoxicity,as well as drug resistance.To address these issues,semi-synthetic approaches for modifying natural AGs have generated new generations of AGs,however,with limited types of modification due to significant challenges in synthesis.This study explores a novel approach that harness the bacterial biosynthetic machinery of gentamicins and kanamycins to create hybrid AGs.This was achieved by glycodiversification of gentamicins via swapping the glycosyltransferase(GT)in their producer with the GT from kanamycins biosynthetic pathway and resulted in the creation of a series of novel AGs,therefore referred to as genkamicins(GKs).The manipulation of the hybrid biosynthetic pathway enabled the targeted accumulation of different GK species and the isolation and characterization of six GK components.These compounds display retained antimicrobial activity against a panel of World Health Organization(WHO)critical priority pathogens,and GK-C2a,in particular,demonstrates low ototoxicity compared to clinical drugs in zebrafish embryos.This study provides a new strategy for diversifying the structure of AGs and a potential avenue for developing less toxic AG drugs to combat infectious diseases.

Fourier-domain-compressed optical time-stretch quantitative phase imaging flow cytometry

Optical time-stretch(OTS)imaging flow cytometry offers a promising solution for high-throughput and highprecision cell analysis due to its capabilities of high-speed,high-quality,and continuous imaging.Compressed sensing(CS)makes it practically applicable by significantly reducing the data volume while maintaining its highspeed and high-quality imaging properties.To enrich the information of the images acquired with CS-equipped OTS imaging flow cytometry,in this work we propose and experimentally demonstrate Fourier-domaincompressed OTS quantitative phase imaging flow cytometry.It is capable of acquiring intensity and quantitative phase images of cells simultaneously from the compressed data.To evaluate the performance of our method,static microparticles and a corn root cross section are experimentally measured under various compression ratios.Furthermore,to show how our method can be applied in practice,we utilize it in the drug response analysis of breast cancer cells.Experimental results show that our method can acquire high-quality intensity and quantitative phase images of flowing cells at a flowing speed of 1 m/s and a compression ratio of 30%.Combined with machine-learning-based image analysis,it can distinguish drug-treated and drug-untreated cells with an accuracy of over 95%.We believe our method can facilitate cell analysis in both scientific research and clinical settings where both high-throughput and high-content cell analysis is required.

The application of CRISPR-Cas in disease diagnosis and treatment

Clustered regularly interspaced short palindromic repeat(CRISPR)has been gaining much attention in the modern medical field and has been widely used for the diagnosis and treatment of diseases in recent years.In this review,we will introduce the application of CRISPR in disease diagnosis and treatment,including its use in detecting pathogens,gene mutations,and genetic diseases,as well as its application in gene therapy for single-gene diseases,cancer,viral infectious diseases,and cardiovascular diseases.Additionally,we will discuss the potential future directions and challenges of CRISPR in the diagnosis and treatment of diseases,and provide a thorough overview of the ways in which CRISPR is used for diagnosing and treating diseases.

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.

Touchable cell biophysics property recognition platforms enable multifunctional blood smart health care

As a crucial biophysical property,red blood cell(RBC)deformability is pathologically altered in numerous disease states,and biochemical and structural changes occur over time in stored samples of otherwise normal RBCs.However,there is still a gap in applying it further to point-of-care blood devices due to the large external equipment(high-resolution microscope and microfluidic pump),associated operational difficulties,and professional analysis.Herein,we revolutionarily propose a smart optofluidic system to provide a differential diagnosis for blood testing via precise cell biophysics property recognition both mechanically and morphologically.Deformation of the RBC population is caused by pressing the hydrogel via an integrated mechanical transfer device.The biophysical properties of the cell population are obtained by the designed smartphone algorithm.Artificial intelligence-based modeling of cell biophysics properties related to blood diseases and quality was developed for online testing.We currently achieve 100%diagnostic accuracy for five typical clinical blood diseases(90 megaloblastic anemia,78 myelofibrosis,84 iron deficiency anemia,48 thrombotic thrombocytopenic purpura,and 48 thalassemias)via real-world prospective implementation;furthermore,personalized blood quality(for transfusion in cardiac surgery)monitoring is achieved with an accuracy of 96.9%.This work suggests a potential basis for next-generation blood smart health care devices.

Personnel protection strategy for healthcare workers in Wuhan during the COVID-19 epidemic

Objective:To identify the effectiveness of a personnel protection strategy in protection of healthcare workers from SARS-CoV-2 infection.Design:During the COVID-19 pandemic,943 healthcare staff sent from Guangzhou to Wuhan to care for patients with suspected/confirmed COVID-19 received infection precaution training before their mission and were equipped with Level 2/3 personal protective equipment(PPE),in accordance with guidelines from the National Health Commission of China.We conducted a serological survey on the cumulative attack rate of SARS-CoV-2 among the healthcare workers sent to Wuhan and compared the seropositive rate to that in local healthcare workers from Wuhan and Jingzhou.Results:Serial tests for SARS-CoV-2 RNA and tests for SARS-CoV-2 immunoglobulin M and G after the 6-8 week mission revealed a zero cumulative attack rate.Among the local healthcare workers inWuhan and Jingzhou of Hubei Province,2.5%(113 out of 4495)and 0.32%(10 out of 3091)had RT-PCR confirmed COVID-19,respectively.The seropositivity for SARS-CoV-2 antibodies(IgG,IgM,or both IgG/IgM positive)was 3.4%(53 out of 1571)in local healthcare workers from Wuhan with Level 2/3 PPE working in isolation areas and 5.4%(126 out of 2336)in healthcare staff with Level 1 PPE working in non-isolation medical areas,respectively.Conclusions and relevance:Our study confirmed that adequate training/PPE can protect medical personnel against SARS-CoV-2.

RNA m^(6) A modification: Mapping methods, roles, and mechanisms in acute myeloid leukemia

N^(6)-Methyladenosine(m^(6)A)is the most abundant modification in eukaryotic mRNA,and plays important biological functions via regulating RNA fate determination.Recent studies have shown that m^(6)A modification plays a key role in hematologic malignancies,including acute myeloid leukemia.The current growth of epitranscriptomic research mainly benefits from technological progress in detecting RNA m^(6)A modification in a transcriptome-wide manner.In this review,we first briefly summarize the latest advances in RNA m^(6)A biology by focusing on writers,readers,and erasers of m^(6)A modification,and describe the development of high-throughput methods for RNA m^(6)A mapping.We further discuss the important roles of m^(6)A modifiers in acute myeloid leukemia,and highlight the identification of potential inhibitors for AML treatment by targeting of m^(6)A modifiers.Overall,this review provides a comprehensive summary of RNA m^(6)A biology in acute myeloid leukemia.