Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy

The advent of single-cell RNA sequencing(scRNA-seq)has provided insight into the tumour immune microenvironment(TIME).This review focuses on the application of scRNA-seq in investigation of the TIME.Over time,scRNA-seq methods have evolved,and components of the TIME have been deciphered with high resolution.In this review,we first introduced the principle of scRNA-seq and compared different sequencing approaches.Novel cell types in the TIME,a continuous transitional state,and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer.Thus,we concluded novel cell clusters of cancerassociated fibroblasts(CAFs),T cells,tumour-associated macrophages(TAMs)and dendritic cells(DCs)discovered after the application of scRNA-seq in TIME.We also proposed the development of TAMs and exhausted T cells,as well as the possible targets to interrupt the process.In addition,the therapeutic interventions based on cellular interactions in TIME were also summarized.For decades,quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer.Summarizing the current findings,we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy,which can subsequently be implemented in the clinic.Finally,we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.

Protective effects of combined treatment with ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury

Despite improvement in cardiopulmonary resuscitation(CPR)performance,cardiac arrest(CA)is still associated with poor prognosis.The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury(I/R).The guidelines for CPR suggest the use of therapeutic hypothermia(TH)as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury.During TH,sedative agents(propofol)and analgesia agents(fentanyl)are commonly used to prevent shiver and pain.However,propofol has been associated with a number of serious adverse effects such as metabolic acidosis,cardiac asystole,myocardial failure,and death.In addition,mild TH alters the pharmacokinetics of agents(propofol and fentanyl)and reduces their systemic clearance.For CA patients undergoing TH,propofol can be overdosed,leading to delayed awakening,prolonged mechanical ventilation,and other subsequent complications.Ciprofol(HSK3486)is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room.Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol.Therefore,we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs.

Estimating global prevalence,incidence,and outcomes of nonalcoholic fatty liver disease from 2000 to 2021:systematic review and meta-analysis

Background:The increasing burden of non-alcoholic fatty liver disease(NAFLD)worldwide imposes an emerging public health issue.We perform the current study to estimate the global prevalence,incidence,disease progression,and clinical outcomes of NAFLD.Methods:A systematic search was conducted in Medline,Embase,Web of Science,Google Scholar,and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021.NAFLD prevalence,incidence,rate of disease progression,and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation.Results:Our search identified 59,156 records,of which 578 studies fulfilled our inclusion criteria.The overall prevalence of NAFLD was 29.38%(95%confidence interval[CI]28.09-30.69)regardless of the diagnostic techniques.Looking at the group in which the diagnosis was made by ultrasound exclusively,the pooled prevalence was 30.49%(95%CI 29.55-31.43).NAFLD has become more prevalent during the year 2011-2021(31.63%,95%CI 30.23-33.04)compared with year 2000-2010(27.94%,95%CI 26.23-29.69).The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26%(95%CI 1.13-21.01),46.49%(95%CI 35.93-57.20),and 46.72%(95%CI 37.57-55.98)in general population,NAFLD patients,and severe/morbidly obese patients,respectively.Based on a total of 110,142 newly developed NAFLD patients,the pooled incident rate was estimated as 46.24 cases per 1000 person-years(95%CI 43.21-49.30).In patients with NAFLD,the incident rate of hepatocellular carcinoma was 1.46(95%CI 0.90-2.03)cases per 1000 person-years.The overall pooled estimate of NAFLD related mortality was 23.91(95%CI 13.55-37.18)death per 1000 person-years.Conclusions:The prevalence of NAFLD is increasing globally.It is contributing to poor clinical outcomes including hepatocellular carcinoma and death.Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe.Registration:PROSPERO,No.CRD42020171104.

TSPAN32 suppresses chronic myeloid leukemia pathogenesis and progression by stabilizing PTEN

We report herein that TSPAN32 is a key node factor for Philadelphia (Ph+) leukemia pathogenesis. We found that TSPAN32expression was repressed by BCR-ABL and ectopic TSPAN32 expression upon Imatinib treatment inhibited the proliferation of Ph+cell lines. Tspan32 overexpression significantly prevented BCR-ABL induced leukemia progression in a murine model and impairedleukemia stem cell (LSC) proliferation. LSCs represent an obstacle for chronic myeloid leukemia (CML) elimination, which continuallyreplenish leukemia cells and are associated with disease relapse. Therefore, the identification of essential targets that contribute tothe survival and self-renewal of LSCs is important for novel curative CML. Mechanistically, TSPAN32 was shown to interact withPTEN, increased its protein level and caused a reduction in PI3K-AKT signaling activity. We also found that TSPAN32 was repressedby BCR-ABL via the suppression of an important transcription factor, TAL1. Ectopic expression of TAL1 significantly increasedTSPAN32 mRNA and protein level, which indicated that BCR-ABL repressed TSPAN32 transcription by decreasing TAL1 expression.Overall, we identified a new signaling axis composed of “BCR-ABL-TAL1-TSPAN32-PTEN-PI3K-AKT”. Our findings furthercomplement the known mechanisms underlying the transformation potential of BCR-ABL in CML pathogenesis. This new signalingaxis also provides a potential means to target PI3K-AKT for CML treatment.

Novel lysosome-targeted anticancer fluorescent agents used in zebrafish and nude mouse tumour imaging

The design of three novel fatty nitrogen mustard-based anticancer agents with fluorophores incorporated into the alkene structure(CXL 118,CXL121,and CXL122)is described in this report.The results indicated that these compounds are selectively located in lysosomes and exhibit effective antitumour activity.Notably,these compounds can directly serve as both reporting and imaging agents in vitro and in vivo without the need to add other fluorescent tagging agents.