Functions and mechanisms of cytosolic phospholipase A_(2)in central nervous system trauma

Central nervous system(CNS)trauma,including traumatic brain injury and spinal cord injury,has a high rate of disability and mortality,and effective treatment is currently lacking.Previous studies have revealed that neural inflammation plays a vital role in CNS trauma.As the initial enzyme in neuroinflammation,cytosolic phospholipase A_(2)(cPLA2)can hydrolyze membranous phosphatides at the sn-2 position in a preferential way to release lysophospholipids andω3-polyunsaturated fatty acid dominated by arachidonic acid,thereby inducing secondary injuries.Although there is substantial fresh knowledge pertaining to cPLA2,in-depth comprehension of how cPLA2 participates in CNS trauma and the potential methods to amelio rate the clinical res ults after CNS trauma are still insufficient.The present review summarizes the latest understanding of how cPLA2 participates in CNS trauma,highlighting novel findings pertaining to how cPLA2 activation initiates the potential mechanisms specifically,neuroinflammation,lysosome membrane functions,and autophagy activity,that damage the CNS after trauma.Moreover,we focused on testing a variety of drugs capable of inhibiting cPLA2 or the upstream pathway,and we explored how those agents might be utilized as treatments to improve the results following CNS trauma.This review aimed to effectively understand the mechanism of cPLA2 activation and its role in the pathophysiological processes of CNS trauma and provide clarification and a new referential framework for future research.

Deletion of 93 bp Far-upstream Fragment of Rice Cytosolic Fructose- 1, 6-Bisphosphatase Promoter Completely Alter Its Expression Pattern

The 1 195 bp 5′ flanking region of rice ( Oryza sativa L.) cytosolic fructose_1, 6_bisphosphatase (cyFBPase) can direct tissue, cell specific expression in transgenic rice. In order to identify sequence elements responsible for the regulation of mesophyll_specific expression, the 5′ flanking regions of -1 195 bp, -1 102 bp, -768 bp, and -644 bp upstream of the translation initiation ATG codon were fused to the reporter gene encoding β_glucuronidase (GUS) and transferred to rice via particle bombardment. Analysis of the 5′ promoter deletions identified that a 93 bp fragment between -1 195 bp and -1 102 bp is essential for directing mesophyll specific expression. High constitutive expression of GUS reporter gene was found in the -768 deletion lines and another two deletion series. These results indicate the great potential utility of the promoter in rice biotechnology.

Isolation of a 1 195 bp 5′-Flanking Region of Rice Cytosolic Fructose-1,6-bisphosphatase and Analysis of Its Expression in Transgenic Rice

A genomic DNA fragment containing the 5'-upstream sequence and part of the open reading frame corresponding to the cytosolic fructose-1,6-bisphosphatase (cyFBPase) cDNA was isolated by Genome Walking. The 1 195 lip 5'-flanking region which started from the translation initiation ATG codon was fused to reporter gene encoding beta-glucuronidase (GUS) and stably transferred to rice via particle bombardment. Strong GUS activity was detected in leaves and leaf sheaths of transgenic rice, but not in culms and roots. Histochemical localization revealed that GUS expression was exclusively restricted to mesophyll cells in transgenic rice. Our results indicate that the 1 195 bp fragment contains all the cis-elements required for directing mesophyll-specific expression pattern in rice.

Effect of Lanthanum(Ⅲ) on Cytosolic Free Calcium in Isolated Rabbit Mature Osteoclasts

The effect of lanthanum （ Ⅲ ） （La^3 ＋ ） on cytosolic free calcium （ [ Ca^2 ＋ ] i ） in isolated rabbit mature osteoclasts was studied with the employment of fluo-3/AM as an intracellular calcium-sensitive fluorescent probe by using a confocal laser scanning microscope. La^3＋ does not alter basal [Ca^2＋ ]i levels and cell spread area at the concentration of 1.00 × 10^- 8 mol· L ^- 1. However, La^3 ＋ at higher concentrations （ 1. 00 × 10^ - 5 and 1.00 × 10^- 7 mol· L^- 1 ） decreases [ Ca^2 ＋ ] i levels and cell spread area, and greater decreases are observed for the higher concentrations of La^3 ＋ . Since [Ca^2 ＋ ]i affects cytoskeleton and the adhesion properties of osteoclasts, our results seem to suggest that La^3 ＋ inhibit bone resorption by decreasing [Ca^2＋]i in rabbit mature osteoclasts.

Lysophosphatidic acid induced nuclear translocation of nuclear factor-κB in Panc-1 cells by mobilizing cytosolic free calcium

AIM: To clarify whether Lysophosphatidic acid (LPA) activates the nuclear translocation of nuclear factor-κB (NF-κB) in pancreatic cancer. METHODS: Panc-1, a human pancreatic cancer cell line, was used throughout the study. The expression of LPA receptors was confirmed by reverse-transcript polymerase chain reaction (RT-PCR). Cytosolic free calcium was measured by fluorescent calcium indicator fura-2, and the localization of NF-κB was visualized by immunofluorescent method with or without various agents, which effect cell signaling. RESULTS: Panc-1 expressed LPA receptors, LPA1, LPA2 and LPA3. LPA caused the elevation of cytosolic free calcium dose-dependently. LPA also caused the nuclear translocation of NF-κB. Cytosolic free calcium was attenuated by pertussis toxin (PTX) and U73122, an inhibitor of phospholipase C. The translocation of NF-κB was similarly attenuated by PTX and U73122, but phorbol ester, an activator of protein kinase C, alone did not translocate NF-κB. Furthermore, the translocation of NF-κB was completely blocked by Ca2+ chelator BAPTA-AM. Thapsigargin, an endoplasmic- reticulum Ca2+-ATPase pump inhibitor, also promoted the translocation of NF-κB. Staurosporine, a proteinkinase C inhibitor, attenuated translocation of NF-κB induced by LPA. CONCLUSION: These findings suggest that protein kinase C is activated endogenously in Panc-1, and protein kinase C is essential for activating NF-κB with cytosolic calcium and that LPA induces the nuclear translocation of NF-κB in Panc-1 by mobilizing cytosolic free calcium.

Induction of defence gene expression by oligogalacturonic acid requires in-creases in both cytosolic calcium and hydrogen peroxide in Arabidopsis thaliana

Responses to oligogalacturonic acid (OGA) were determined in transgenic Arabidopsis thaliana seedlings expressing the calcium reporter protein aequorin. OGA stimulated a rapid, substantial and transient increase in the concentration of cytosolic calcium ([Ca2+]cyt) that peaked after ca. 15 s. This increase was dose-dependent, saturating at ca. 50 μg Gal equiv/ml of OGA. OGA also stimulated a rapid generation of H2O2. A small, rapid increase in H2O2 content was followed by a much larger oxidative burst, with H2O2 content peaking after ca. 60 min and declining thereafter. Induction of the oxidative burst by OGA was also dose-dependent, with a maximum response again being achieved at ca. 50 μg Gal equiv/mL. Inhibitors of calcium fluxes inhibited both increases in [Ca2+]cyt and [H2O2], whereas inhibitors of NADPH oxidase blocked only the oxidative burst. OGA increased strongly the expression of the defence-related genes CHS,GST, PAL and PR-1. This induction was suppressed by inhibitors of calcium flux or NADPH oxidase, indicating that increases in both cytosolic calcium and H2O2 are required for OGA-induced gene expression.

Cytosolic phospholipase A2α modulates cell-matrix adhesion via the FAK/paxillin pathway in hepatocellular carcinoma

Objective: To explore the effect of cytosolic phospholipase A2α(cPLA2α) on hepatocellular carcinoma(HCC) cell adhesion and the underlying mechanisms.Methods: Cell adhesion, detachment, and hanging-drop assays were utilized to examine the effect of cPLA2α on the cell-matrix and cell-cell adhesion. Downstream substrates and effectors of cPLA2α were screened via a phospho-antibody microarray.Associated signaling pathways were identified by the functional annotation tool DAVID. Candidate proteins were verified using Western blot and colocalization was investigated via immunofluorescence. Western blot and immunohistochemistry were used to detect protein expression in HCC tissues. Prognosis evaluation was conducted using Kaplan-Meier and Cox-proportional hazards regression analyses.Results: Our findings showed that cPLA2α knockdown decreases cell-matrix adhesion but increases cell-cell adhesion in HepG2 cells. Microarray analysis revealed that phosphorylation of multiple proteins at specific sites were regulated by cPLA2α. These phosphorylated proteins were involved in various biological processes. In addition, our results indicated that the focal adhesion pathway was highly enriched in the cPLA2α-relevant signaling pathway. Furthermore, cPLA2α was found to elevate phosphorylation levels of FAK and paxillin, two crucial components of focal adhesion. Moreover, localization of p-FAK to focal adhesions in the plasma membrane was significantly reduced with the downregulation of cPLA2α. Clinically, cPLA2α expression was positively correlated with p-FAK levels. Additionally, high expression of both cPLA2α and p-FAK predicted the worst prognoses for HCC patients.Conclusions: Our study indicated that cPLA2α may promote cell-matrix adhesion via the FAK/paxillin pathway, which partly explains the malignant cPLA2α phenotype seen in HCC.

Real-time Assessment of Cytosolic, Mitochondrial, and Nuclear Calcium Levels Change in Rat Pheochromocytoma Cells during Pulsed Microwave Exposure Using a Genetically Encoded Calcium Indicator

Little information is available about the effects of exposure to pulsed microwaves on neuronal Ca^2＋ signaling under non-thermal conditions. In this study, rat pheochromocytoma （PC12） cells were exposed to pulsed microwaves for 6 min at a specific absorption rate （SAR） of 4 W/kg to assess possible real-time effects. During microwave exposure, free calcium dynamics in the cytosol, mitochondria, and nucleus of cells were monitored by time-lapse microfluorimetry using a genetically encoded calcium indicator （ratiometric-pericam, ratiometric-10ericam-mt,

Effects of 3, 4-Dihydroxyacetophenone on Cytosolic Calcium in Pulmonary Artery Endothelial and Smooth Muscle Cells during Acute Hypoxia

Summary: The effects of 3, 4-Dihydroxyacetophenone (3, 4-DHAP) on cytosolic free calcium [Ca~2+ ]_i in pulmonary artery endothelia (PAECs) and smooth muscle cells (PASMCs) during acute hypoxia were studied. Porcine pulmonary artery endothelial and smooth muscle cells (PASMCs) were cultured primarily, and they were divided into 4 groups: groups incubated under normoxia or hypoxia and those with or without treatment with 3, 4-DHAP. The [Ca~2+ ]_i of both PAECs and PASMCs was measured by determining the fluorescence of fura 2 AM on spetrofluorometer. Our results showed that hypoxia caused significant elevation of [Ca~2+ ]_i, in both PAECs and PASMCs, 3, 4-DHAP could attenuate the hypoxic elevation of [Ca~2+ ]_i only in PASMCs but not in PAECs. It is concluded that 3, 4-DHAP decreases the hypoxic elevation of [Ca~2+ ]_i in PASMCs. This might contribute to its inhibitory effect on hypoxic pulmonary vasoconstriction.

Refractory very early-onset inflammatory bowel disease associated with cytosolic isoleucyl-tRNA synthetase deficiency:A case report

BACKGROUND Aminoacyl tRNA synthetases/ligases(ARSs)are highly conserved enzymes involved in attaching amino acids to tRNA promoting protein synthesis.Although deficiencies of ARSs localized to the mitochondria classically present with neuropathology,the clinical features of cytosolic ARS deficiencies are more variable.They have previously been associated with neonatal hepatitis,but never with early-onset inflammatory bowel disease.CASE SUMMARY A nine-year-old Bangladeshi boy presented with neonatal liver failure and deranged clotting,transaminitis and cholestasis.His parents were first cousins.Two older brothers and a sister were well.The patient suffered from loose stools from early infancy which became more troublesome and persistent from five years old with ten bloody motions a day.Repeated endoscopies showed persistent pancolitis,which was refractory to mesalazine,corticosteroids,azathioprine,sirolimus and anti-TNF(adalimumab)therapy,but has improved recently with subcutaneous methotrexate.Whole Genome Sequencing revealed a novel pathogenic missense variant(c.290A>G)in the cytosolic isoleucyl-tRNA synthetase gene,leading to an amino acid substitution(p.Asp97Gly).Pathogenic variants in other genes associated with inflammatory bowel disease(IBD)(ADAM17,EGFR,FOXP3,IL10RA,IL10RB,IL21R,NCF4,STAT3)were excluded.Cytokine assays demonstrated markedly elevated IL-2,IL-5,IL-13,IL-9 and IL-10 by the patient’s CD4+T-cells,while IL-17A,IL-17F,IFNβwere lower,and TNFαnot significantly different when compared to healthy controls.CONCLUSION This case report provides evidence that recessive mutations in cytosolic isoleucyltRNA synthetase are a novel monogenic cause of IBD,which should be considered,particularly in infants and children with a history of neonatal hepatitis and very early-onset IBD poorly responsive to treatment.

Overexpression of Brassica napus cytosolic fructose-1,6-bisphosphatase and sedoheptulose-1,7-bisphosphatase genes significantly enhanced tobacco growth and biomass

Elevated activities of cytosolic fructose-1,6-bisphosphatase(cyFBPase) and sedoheptulose-1,7-bisphosphatase(SBPase)are associated with higher yields in plants. In this study, the expression levels of the cyFBPase and SBPase genes were increased by overexpressing rape(Brassica napus) cDNA in tobacco(Nicotiana tabacum) plants. The transgenic plants coexpressing cy FBPase and SBPase(TpFS), or expressing single cy FBPase(TpF) or SBPase(TpS) had 1.77-, 1.55-, 1.23-fold cyFBPase and 1.45-, 1.12-, 1.36-fold SBPase activities as compared to the wild-type(WT), respectively. Photosynthesis rates of TpF, TpS and TpFS increased 4, 20 and 25% compared with WT plants. The SBPase and cyFBPase positively regulated each other and functioned synergistically in transgenic tobacco plants. In addition, the sucrose contents of the three transgenic plants were higher than that of WT plants. The starch accumulation of the TpFS and TpS plants was improved by 53 and 37%, but slightly decreased in TpF plants. Moreover, the transgenic tobacco plants harbouring SBPase and/or cyFBPase genes showed improvements in their growth, biomass, dry weight, plant height, stem diameter, leaf size,flower number, and pod weight. In conclusion, co-expression of SBPase and cyFBPase may pave a new way for improving crop yield in agricultural applications.

Cytosolic Phospholipase A2 and Its Role in Cancer

Cytosolic phospholipase A2α （cPLA2α） catalyzes the release of arachidonic acid （AA） and lysophosphoglyceride from membrane phospholipids. Although the roles of AA and eicosanoids in cellular viability, the processes of inflammation and cancer cell development have been extensively studied, the function of cPLA2α in the processes of inflammation and cancer cell development is not clear. This review summarizes published evidences for the biochemical properties and regulatory mechanisms of cPLA2α. The potential for use of cPLA2α as a novel diagnostic target and predictive biomarker for tumors is also discussed.

Mitochondrial malfunction in vanishing white matter disease： a disease of the cytosolic translation machinery

Vanishing white matter （VWM） disease - a disease of the cytosolic translation machinery： VWM is a recessive genet- ic neurodegenerative disease caused by mutations in any of the five genes encoding the subunits of translation initiation factor 2B （eIF2B） （Leegwater et al., 2001; OMIM 306896）.

Effects ofβ_2-Adrenergic Antagonist on Cytosolic Ca^(2+) in Ventricular Myocytes from Infarcted Rat Heart

Objectives To investigate the effects of β2-adrenergic antagonist on cytosolic Ca^2 ＋ （[Ca^2＋ ]i） in ventricular myocytes from infarcted rat heart. Methods A ligature was placed around left anterior descending coronary artery of rat hearts. Rats in the control group were sham-operated. Cardiomyocytes were dissociated at two, four, eight weeks after myocardial infarction （MI） and [Ca^2＋]i was measured via fura-2 fluorescence. The response of cardiomyocytes to isoproterenol in presence or absence of betal-adrenergic antagonist atenolol, beta2-adrenergic antagonist ICI118, 551 or non-selective β1, 2- adrenergic antagonists propranolol was examined. Results The followings were found that ICI 118, 551 had no significant effects on the rise of [Ca^2＋]i induced by isoproterenol in normal ventricular myocytes （P 〉 0.05）, ICI118, 551 only significantly attenuated the rise of [Ca^2＋]i induced by isoproterenol at four weeks and eight weeks after MI （24.5%±5.7% vs 57.8% ± 13.2%, P〈 0.01; 12.2%±7.9% vs 44.6%±11.3%, P〈 0.01）. Atenolol had suppressive effects only in the control group and the post-MI group of two weeks （P 〈 0.05）, and propranolol had suppressive effects in the control and all the three post-MI groups （P 〈 0.01）. Conclusions Beta2-adrenergic antagonist ICI118, 551 may exert negative effects on Ca^2＋ overload initiated by sympathetic stimulation after MI.

Metabolism of minor isoforms of prion proteins Cytosolic prion protein and transmembrane prion protein

Transmissible spongiform encephalopathy or prion disease is triggered by the conversion from cellular prion protein to pathogenic prion protein. Growing evidence has concentrated on prion protein configuration changes and their correlation with prion disease transmissibility and patho- genicity. In vivo and in vitro studies have shown that several cytosolic forms of prion protein with specific topological structure can destroy intracellular stability and contribute to prion protein pathogenicity. In this study, the latest molecular chaperone system associated with endoplasmic re- ticulum-associated protein degradation, the endoplasmic reticulum resident protein quality-control system and the ubiquitination proteasome system, is outlined. The molecular chaperone system directly correlates with the prion protein degradation pathway. Understanding the molecular mechanisms will help provide a fascinating avenue for further investigations on prion disease treatment and prion protein-induced neurodegenerative diseases.

Procainamide inhibits A23187－induced human platelet aggregation and increase in cytosolic free－Ca2＋ in the cells

Effects of procainamide (PA) on human platelet aggregation and the cytosolic free-Ca2+ concentration ([Ca2+]) were investigated in vitro. PA at doses of 8.5 , 34 and 136 μmol·L-1 could inhibit the human platelet aggregation induced by 0. 5 μmol · L-1 A23187 with a good concentration -effect relationship. One min and maximal aggregation rates were also inhibited ( P<0. 01 ,vs control). The [Ca2+], was decreased in the presence of PA ,and the changes of [Ca2+], showed a significant linear correlation with 1 min or maximal aggregation rate (P<0.05). These results suggest that the mechanisms of PA inhibiting platelet aggregation relate to the decrease of [Ca2+].

Time-dependent changes of glial fibriliary acidic protein and cytosolic phospholipase A2 in hippocampal area of focal cerebral ischemia/reperfusion in rats

BACKGROUND： Interaction between astrocyte and neuron may two-dimensionally influence on ischemic injury; however, glial fibriliary acidic protein （GFAP） and cytosolic phospholipase A2 （cPLA2） are both important markers to reflect changes of astrocyte and neuron after cerebral ischemia, respectively. OBJECTIVE： To observe the changes of GFAP and positive cPLA2 cells in hippocampal area of model rats with focal cerebral ischemia in various phases of cerebral ischemia/reperfusion. DESIGN ： Randomized contrast observation SETTING： Department of Basic Medical Science of Human Anatomy and Histology ＆ Embryology, Medical College of Wuhan Polytechnic University; Faculty Medical College of Wuhan University. MATERIALS： The experiment was carried out in the Department of Basic Medical Science, Medical College of Wuhan Industry College from May to June 2004. A total of 28 healthy SD rats of either gender and weighing 200-250 g were provided by Animal Department of Medical College of Jianghan University. METHODS： All 28 rats were randomly divided into 7 groups, including sham operation group, 2-, 6-, 12-, 24- and 48-reperfusion groups, and triphenyltetrazolium chloride （TTC） group, with 4 in each group. Two hours after ischemia, ischemia/reperfusion models were established in left middle cerebral artery （MCA）; common carotid artery was ligated and line cork was inserted into it with the depth of （1.8±0.5） cm. Rats in sham operation group were inserted with the depth of 1.0 cm, and other operations were as the same as those in 2-hour ischemia/reperfusion groups. Models in TTC group were established as the same as those in 2-hour ischemia/24-hour reperfusion group, and they were used to evaluate the therapeutic effect. Changes of GFAP and cPLA2 in hippocampal area in various phases were detected with immunohisto- chemical method. MAIN OUTCOME MEASURES ： Changes of GFAP and positive cPLA2 cells in hippocampal area of rats with focal cerebral ischemia in various phases of ischemia/reperfusion. RESULTS： All 28 rats were involved in the final analysis without any loss. （1） Animal models successfully showed the effect of focal cerebral ischemia. （2） Changes of GFAP and cPLA2 in hippocampal area in various phases： Two hours after ischemia/reperfusion, changes of GFAP and cPLA2 were increased gradually, reached at peak at 24 hours, and decreased gradually. CONCLUSION ： Courses of GFAP and cPLA2 are changed at the onset of focal cerebral ischemia, and this suggests that both of them participate in injury or protection of brain tissue of focal cerebral ischemia.

Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice

Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation,known as meta-inflammation.This state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver disease.Pyruvate is a glycolytic metabolite and a crucial node in various metabolic pathways.However,its role and molecular mechanism in obesity and associated complications are obscure.In this study,we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain,white adipose tissue inflammation,and metabolic dysregulation.To identify the target proteins of pyruvate,drug affinity responsive target stability was employed with proteomics,cellular thermal shift assay,and isothermal drug response to detect the interactions between pyruvate and its molecular targets.Consequently,we identified cytosolic phospholipase A2(cPLA2)as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity,white adipose tissue inflammation,and hepatic steatosis in a cPLA2-dependent manner.Studies with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated,confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and obesity.Overall,our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity but it also sheds light on the mechanism of its action.Pyruvate’s prior clinical use indicates that it can be considered a safe and viable alternative for obesity,whether consumed as a dietary supplement or as part of a regular diet.

Research Article Dynamically crosslinked nanocapsules for the efficient and serumresistant cytosolic protein delivery

Intracellular protein delivery is critical to the development of protein-based biopharmaceuticals and therapies.However,current delivery vectors often suffer from complicated syntheses,low generality among various proteins,and insufficient serum stability.Herein,we developed an enlightened cytosolic protein delivery strategy by dynamically crosslinking epigallocatechin gallate(EGCG),low-molecular-weight polyethylenimine(PEI 1.8k),and 2-acetylphenylboric acid(2-APBA)on the protein surface,hence forming the EPP-protein nanocapsules(NCs).EGCG enhanced protein encapsulation via hydrogen bonding,and reduced the positive charge density of PEI to endow the NCs with high serum tolerance,thereby enabling effective cellular internalization in serum.The formation of reversible imine and boronate ester among 2-APBA,EGCG,and PEI 1.8k allowed acid-triggered dissociation of EPP-protein NCs in the endolysosomes,which triggered efficient intracellular release of the native proteins.Such strategy therefore showed high efficiency and universality for diversities of proteins with different molecular weights and isoelectric points,including enzyme,toxin,antibody,and CRISPR(clustered regularly interspaced short palindromic repeats)-Cas9 ribonucleoprotein(RNP),outperforming the commercial protein transduction reagent PULSin and RNP transfection reagent lipofectamine CMAX.Moreover,intravenously(i.v.)injected EPP-saporin NCs efficiently delivered saporin into 4T1 tumor cells to provoke robust antitumor effect.This simple,versatile,and robust cytosolic protein delivery system holds translational potentials for the development of protein-based therapeutics.

Catechol-Based Polymers with High Efficacy in Cytosolic Protein Delivery

Polymers have been widely proposed as carriers for cytosolic protein delivery despite multiple barriers such as protein binding,cell internalization,and endosome escape during cytosolic delivery.Inspired by the strong binding affinity of natural polyphenols with proteins and cell membranes,herein we propose polyphenol modification to improve the efficacy of the protein delivery of cationic polymers.Catecholmodified dendrimers with balanced hydrophobic and hydrogen-bonding interactions show the highest efficacy for various cargo proteins and peptides while the pyrogallol-grafted ones exhibit the lowest efficacy due to increased ligand hydrophilicity.The catechol-based polymers efficiently deliver various bioactive proteins into the cytosol of live cells,exerting biofunctions after intracellular release,and successfully transmittingα-chymotrypsin into tumor cells in vivo to inhibit tumor growth.This study proves that polycatechols can serve as a family of highly efficient carriers for delivery of macromolecular biopharmaceuticals.