Biomechanical analysis of spinal cord injury during scoliosis correction surgery.

Introduction: Surgical correction is a common treatment for severe scoliosis. Due to the significant spinal deformation that occurs with this condition, spinal cord injuries during corrective surgery can occur, sometimes leading to paralysis. Methods: Such events are associated with biomechanical changes in the spinal cord during surgery, however, their underlying mechanisms are not well understood. Six patient-specific cases of scoliosis either with or without spinal complications were examined. Finite element analyses (FEA) were performed to assess the dynamic changes and stress distribution of spinal cords after surgical correction. The FEA method is a numerical technique that simplifies problem solving by replacing complex problem solving with simplified numerical computations. Results: In four patients with poor prognosis, there was a concentration of stress in the spinal cord. The predicted spinal cord injury areas in this study were consistent with the clinical manifestations of the patients. In two patients with good prognosis, the stress distribution in the spinal cord models was uniform, and they showed no abnormal clinical manifestations postoperatively. Discussion: This study identified a potential biomechanical mechanism of spinal cord injury caused by surgical correction of scoliosis. Numerical prediction of postoperative spinal cord stress distribution might improve surgical planning and avoid complications.

Postnatal growth restriction impairs rat lung structure and function.

The negative impact of nutritional deficits in the development of bronchopulmonary dysplasia is well recognized, yet mechanisms by which nutrition alters lung outcomes and nutritional strategies that optimize development and protect the lung remain elusive. Here, we use a rat model to assess the isolated effects of postnatal nutrition on lung structural development without concomitant lung injury. We hypothesize that postnatal growth restriction (PGR) impairs lung structure and function, critical mediators of lung development, and fatty acid profiles at postnatal day 21 in the rat. Rat pups were cross-fostered at birth to rat dams with litter sizes of 8 (control) or 16 (PGR). Lung structure and function, as well as serum and lung tissue fatty acids, and lung molecular mediators of development, were measured. Male and female PGR rat pups had thicker airspace walls, decreased lung compliance, and increased tissue damping. Male rats also had increased lung elastance, increased lung elastin protein abundance, and lysol oxidase expression, and increased elastic fiber deposition. Female rat lungs had increased conducting airway resistance and reduced levels of docosahexaenoic acid in lung tissue. We conclude that PGR impairs lung structure and function in both male and female rats, with sex-divergent changes in lung molecular mediators of development.

A rapid and robust method to determine the key parameters of formaldehyde emissions from building and vehicle cabin materials: Principle, multi-source application and exposure assessment.

The ubiquity of formaldehyde emitted in indoor and in-cabin environments can adversely affect health. This study proposes a novel full-range C-history method to rapidly, accurately and simultaneously determine the three key parameters (initial emittable concentration, partition coefficient, diffusion coefficient) that characterize the emission behaviors of formaldehyde from indoor building and vehicle cabin materials, by means of hybrid optimization. The key parameters of formaldehyde emissions from six building materials and five vehicle cabin materials at various temperatures, were determined. Independent experiments and sensitivity analysis verify the effectiveness and robustness of the method. We also demonstrate that the determined key parameters can be used for predicting multi-source emissions from different material combinations that are widely encountered in realistic indoor and in-cabin environments. Furthermore, based on a constructed vehicle cabin and the determined key parameters, we make a first attempt to estimate the human carcinogenic potential (HCP) of formaldehyde for taxi drivers and passengers at two temperatures (25 °C, 34 °C). The HCP for taxi drivers at both temperatures exceeds 10-6 cases, indicating relatively high potential risk. This study should be helpful for pre-evaluation of indoor and in-cabin air quality, and can assist designers in selecting appropriate materials to achieve effective source control.

Circular RNA ITCH Is a Tumor Suppressor in Clear Cell Renal Cell Carcinoma Metastasis through miR-106b-5p/PDCD4 Axis.

High metastasis of clear cell renal cell carcinoma (ccRCC) significantly influenced survival rate of ccRCC patients. Here, we intended to investigate the impacts of circular RNA ITCH (circ-ITCH) on the metastasis of ccRCC. The expression of circ-ITCH in ccRCC tissues and cells was evaluated utilizing qRT-PCR. Transwell assay and wound healing were applied to investigate migration and invasion of ccRCC cells. Target gene prediction and screening and luciferase reporter gene assays were utilized to assess downstream target genes of circ-ITCH. Western blot was utilized to detect metastasis-related protein expression. A xenograft tumor model was established to evaluate the role of circ-ITCH in vivo. Results showed that circ-ITCH was low expressed in ccRCC tissues and cells. Downregulation circ-ITCH promoted cell migration, but overexpressing circ-ITCH inhibited cell migration and invasion in OSRC-2 and SW839 cells. Mechanism investigations claimed that circ-ITCH exerted its metastasis-inhibitory activity via sponging miR-106b-5p and regulating the expression of PDCD4. Conclusively, circ-ITCH suppresses ccRCC metastasis by enforcing PDCD4 expression through binding miR-106b-5p. circ-ITCH may function as a novel diagnostic target to suppress ccRCC metastasis.

The risk factors of gestational hypertension in patients with polycystic ovary syndrome: a retrospective analysis.

BACKGROUND: The hypertensive disorders complicating pregnancy (HDCP) is common in patients with polycystic ovary syndrome (PCOS), yet the potential influencing factors remained unclear. We aimed to assess the independent risk factors of HDCP in patients with PCOS, to provide clinical evidences for the management of PCOS. METHODS: Pregnant PCOS patients treated in our hospital from June 1, 2018 to November 30, 2020 were approached. The personal and clinical characteristics of patients with and without gestational hypertension were evaluated. Logistic regressions were conducted to identify the independent risk factors of HDCP, Receiver operating characteristics (ROC)curve analysis was conducted to evaluate the predicting value. RESULTS: A total of 188 PCOS patients were included, the incidence of HDCP in patients with PCOS was 27.66 %. There were significant differences in the age, BMI, family history of hypertension, the history of adverse pregnancy, history of contraceptive pills use and family history of HDCP between HDCP group and no-HDCP group (all p < 0.05), and there were no significant differences in the family history of diabetes, multiple pregnancy and long-term smoking history between HDCP group and no-HDCP group (all p > 0.05). Age ≥ 27y(OR2.048, 95 %CI1.121 ~ 3.208), BMI ≥ 24 kg/m2(OR1.463, 95 %CI1.069 ~ 2.011), family history of hypertension(OR2.129, 95 %CI1.093 ~ 3.042), the history of adverse pregnancy(OR2.435, 95 %CI1.264 ~ 4.085), history of contraceptive pills use(OR3.806, 95 %CI1.184 ~ 6.102), family history of HDCP(OR1.934, 95 %CI1.016 ~ 2.774) were the independent risk factors of HDCP in patients with PCOS (all p < 0.05). ROC curve analyses indicated that those factors had good predictive value on HDCP in PCOS patients. CONCLUSIONS: The incidence of HDCP in PCOS patients is relatively high. In clinical practice, medical workers should carry out early prevention and intervention measures for these risk factors to reduce the incidence of HDCP.

Maternal high-fat diet up-regulates type-1 cannabinoid receptor with estrogen signaling changes in a sex- and depot- specific manner in white adipose tissue of adult rat offspring.

PURPOSE: Obesity and high-fat (HF) diet are associated with over activation of the endocannabinoid system (ECS). We have demonstrated that maternal HF diet induces early obesity and modulates cannabinoid signaling in visceral (VIS) and subcutaneous (SUB) white adipose tissue (WAT) in weanling rat offspring. We hypothesized that perinatal maternal HF diet would program the expression of ECS in adipose tissue in a long-term way in parallel to alterations in epigenetic markers and sex hormone signaling. METHODS: Progenitor female rats received control diet (C, 9% fat) or isocaloric high-fat diet (HF, 28% fat) for 8 weeks before mating, gestation, and lactation. All pups were weaned to C diet and they were euthanized at 180 days old. RESULTS: Maternal HF diet induced overweight and increased SUB WAT mass of male and female adult offspring. Maternal HF diet induced hypertrophy of VIS and SUB adipocytes only in female offspring associated with increased type 1 cannabinoid receptor protein (CB1) and mRNA (Cnr1) levels. These changes were associated with increased estrogen receptor α binding to Cnr1 promoter in SUB WAT of adult female offspring, which may contribute to higher expression of Cnr1. CONCLUSION: Increased CB1 signaling in adipose tissue might contribute to higher adiposity programmed by maternal HF diet because endocannabinoids stimulate the accumulation of fat in the adipose tissue. Our findings provide molecular insights into sex-specific targets for anti-obesity therapies based on the endocannabinoid system.

Prognostic Value of Long Noncoding RNA SPRY4-IT1 on Survival Outcomes in Human Carcinomas: A Systematic Review and Meta-Analysis with TCGA Database.

BACKGROUND: Emerging evidences have shown that long noncoding RNA SPRY4-IT1 can be aberrantly expressed in human cancers, and it could be an unfavorable prognostic factor in cancer patients. However, the prognostic mechanism of SPRY4-IT1 is still unclear. This study is aimed at evaluating its potential predictive value for cancer prognosis. METHODS: We thoroughly searched PubMed, Embase, Web of Science, and MEDLINE databases so as to explore the relationship between SPRY4-IT1 expression and cancer prognosis value. Then, TCGA datasets were used to validate the results of our meta-analysis. RESULTS: In all, seventeen studies involving 1650 patients were included in this meta-analysis. Pooled results showed that high expression of SPRY4-IT1 was significantly correlated with poor OS (HR = 1.96, 95% confidence interval (CI) = 1.47-2.62, P < 0.001) in cancer patients. Furthermore, exploration of TCGA dataset further validated that SPRY4-IT1 was aberrantly expressed in various cancers, which partially confirmed our results in this meta-analysis. CONCLUSIONS: The present systematic review and meta-analysis implicated that the aberrant expressions of lncRNA SPRY4-IT1 were strongly associated with clinical survival outcomes in various cancers and therefore might serve as a promising biomarker for predicting prognosis of human cancers.

A smart theranostic platform for photoacoustic and magnetic resonance dual-imaging-guided photothermal-enhanced chemodynamic therapy.

The use of smart theranostic agents in multimodal imaging and treatment is a promising strategy to overcome the limitations of single mode diagnosis and treatment, and can greatly improve the diagnosis and effects of treatment. In this study, a gold@manganese dioxide (Au@MnO2) core-shell nanostructure was designed as a glutathione (GSH)-triggered smart theranostic agent for photoacoustic and magnetic resonance (MR) dual-imaging-guided photothermal-enhanced chemodynamic therapy. Both in vitro and in vivo experiments demonstrated not only that the photoacoustic and MR imaging function of Au@MnO2 could be activated by a high endogenous GSH concentration, but also that after being triggered by the endogenous GSH, Au@MnO2 had an excellent synergistic treatment effect in photothermal-enhanced chemodynamic therapy under the guidance of photoacoustic and MR imaging. This study demonstrated that the use of GSH-triggered Au@MnO2 in photoacoustic and MR dual-imaging-guided photothermal-enhanced chemodynamic therapy is a smart theranostic nanoplatform for the accurate diagnosis and efficient treatment of cancer.

Maternal Tobacco Smoke Exposure Causes Sex-Divergent Changes in Placental Lipid Metabolism in the Rat.

Maternal tobacco smoke exposure (MTS) affects fetal acquisition of long-chain polyunsaturated fatty acids (LCPUFA) and increases the risk of obesity and cardio-metabolic disease in the offspring. Alterations in fetal LCPUFA acquisition in maternal smoking are mediated by the placenta. The handling of LCPUFA by the placenta involves protein-mediated transfer and storage. Molecular mediators of placental LCPUFA handling include PPARγ and the fatty acid transport proteins. We previously demonstrated, in a rat model, that MTS results in programming of adult-onset obesity and metabolic disease in male, but not female, offspring. In this study, we test the hypothesis that in utero MTS exposure alters placental structure, placental LCPUFA handling, and fetal fatty acid levels, in a sex-divergent manner. We exposed pregnant rats to tobacco smoke from embryonic day 11 to term gestation. We measured placental and fetal fatty acid profiles, the systolic/diastolic ratio (SD ratio), placental histology, and expression of molecular mediators in the placenta. Our primary finding is that MTS alters fatty acid profiles in male, but not female fetuses and placenta, including increasing the ratio of omega-6 to omega-3 fatty acids. MTS also increased SD ratio in male, but not female placenta. In contrast, the expression of PPARγ and FATPs was upregulated in female, but not male placenta. We conclude that MTS causes sex-divergent changes in placental handling of LCPUFA in the rat. We speculate that our results demonstrate an adaptive response to MTS by the female placenta.

Maternal high-fat diet impairs leptin signaling and up-regulates type-1 cannabinoid receptor with sex-specific epigenetic changes in the hypothalamus of newborn rats.

Maternal nutritional imbalances trigger developmental adaptations involving early epigenetic mechanisms associated with adult chronic disease. Maternal high-fat (HF) diet promotes obesity and hypothalamic leptin resistance in male rat offspring at weaning and adulthood. Leptin resistance is associated with over activation of the endocannabinoid system (ECS). The ECS mainly consists of endocannabinoids derived from n-6 fatty acids and cannabinoid receptors (CB1 coded by Cnr1 and CB2 coded by Cnr2). The CB1 activation in hypothalamus stimulates feeding and appetite for fat while CB2 activation seems to play an immunomodulatory role. We demonstrated that maternal HF diet increases hypothalamic CB1 in male offspring while increases CB2 in female offspring at birth, prior to obesity development. However, the molecular mechanisms behind these changes remain unexplored. We hypothesized that maternal HF diet would down-regulate leptin signaling and up-regulate Cnr1 mRNA levels in the hypothalamus of the offspring at birth, associated with sex-specific changes in epigenetic markers and sex steroid signaling. To test our hypothesis, we used progenitor female rats that received control diet (C, 9% fat) or isocaloric high-fat diet (HF, 28% fat) from 8 weeks before mating until delivery. Blood, hypothalamus and carcass from C and HF male and female offspring were collected for biochemical and molecular analyses at birth. Maternal HF diet down-regulated the transcriptional factor STAT3 in the hypothalamus of male and female offspring, but induced hypoleptinemia only in males and decreased phosphorylated STAT3 only in female offspring. Because leptin acts through STAT3 pathway to inhibit central ECS, our results suggest that leptin pathway impairment might contribute to increased levels of Crn1 mRNA in hypothalamus of both sex offspring. Besides, maternal HF diet increased the histone acetylation percentage of Cnr1 promoter in male offspring and increased the androgen receptor binding to the Cnr1 promoter, which can contribute to higher expression of Cnr1 in newborn HF offspring. Maternal HF diet increased plasma n6 to n3 fatty acid ratio in male offspring, which is an important risk factor to metabolic diseases and might indicate an over activation of endocannabinoid signaling. Thus, although maternal HF diet programs a similar phenotype in adult offspring of both sexes (obesity, hyperphagia and higher preference for fat), here we showed that molecular mechanisms involving leptin signaling, ECS, epigenetic markers and sex hormone signaling were modified prior to obesity development and can differ between newborn male and female offspring. These observations may provide molecular insights into sex-specific targets for anti-obesity therapies.

Genetic polymorphisms of melatonin receptors 1A and 1B may result in disordered lipid metabolism in obese patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a condition in which a woman's levels of the sex hormones (estrogen and progesterone) are out of balance, leading to the growth of ovarian cysts. PCOS can affect the menstrual cycle, fertility, cardiac function and even appearance of women. Therefore, we aimed to explore the genetic polymorphism of the melatonin receptors 1A and 1B in obese patients with PCOS to identify a new theoretical basis for its treatment. Patients presenting with PCOS (n=359) were enrolled and classified into an obese OB­PCOS group [body mass index (BMI) of PCOS patients ≥25 kg/m2] or a nonobese NOB­PCOS group, and 215 oviduct infertile patients who experienced normal ovulation were used as the control group. All baseline characteristics, endocrine hormone levels, lipid and glucose metabolism, and insulin indices were measured. The genotypes of rs2119882 within the MTNR1A gene and of rs10830963 within the MTNR1B gene were determined by PCR­RFLP; the genotype frequency and the difference in the distribution of allele frequency were compared. For rs2119882, C allele carriers who were not diagnosed with PCOS had an increased risk of developing PCOS, and C allele carriers with PCOS had an increased risk of developing OB­PCOS. For rs10830963, G allele carriers who were not diagnosed with PCOS had an increased risk of developing PCOS. The TT genotype in rs2119882 and the CC genotype in rs10830963 were protective factors for OB­PCOS, and increased levels of LH, testosterone, and estradiol and abnormal menstruation were key risk factors for PCOS. Furthermore, the TT genotype at the rs2119882 site was the key protective factor for OB­PCOS patients. Our study found that MTNR1A rs2119882 and MTNR1B rs10830963 could increase the risk for PCOS and cause glycolipid metabolism disorder in PCOS patients.

Protein stabilizer, NDSB-195, enhances the dynamics of the ß4 -α2 loop of ubiquitin.

Non-detergent sulfobetaines (NDSBs) are a new group of small, synthetic protein stabilizers, which have advantages over classical compatible osmolytes, such as polyol, amines, and amino acids: they do not increase solution viscosity, unlike polyols, and they are zwitterionic at all pH ranges, unlike amines and amino acids. NDSBs also facilitate the crystallization and refolding of proteins. The mechanism whereby NDSBs exhibit such activities, however, remains elusive. To gain insight into this mechanism, we studied, using nuclear magnetic resonance (NMR), the effects of dimethylethylammonium propane sulfonate (NDSB-195) on the dynamics of ubiquitin, on which a wealth of information has been accumulated. By analyzing the line width of amide proton resonances and the transverse relaxation rates of nitrogen atoms, we found that NDSB-195 enhances the microsecond-millisecond dynamics of a ß4 -α2 loop of ubiquitin. Although those compounds that enhance protein dynamics are generally considered to destabilize protein molecules, NDSB-195 enhanced the stability of ubiquitin against guanidium chloride denaturation. Thus, the simultaneous enhancement of stability and flexibility by a single compound can be attained.

Refolding additive, dimethylbenzylammonium propane sulfonate (NDSB- 256), accelerates gly-pro cis-trans isomerization.

Proline cis-trans isomerization plays a key role in the rate-determining steps of protein folding, and many different peptide-proline cis-trans isomerases (PPIases) catalyze this reaction. The acceleration of isomerization would be beneficial for in vitro refolding of protein preparations for industrial and research purposes. So we analyzed whether low-molecular-weight compounds that have been reported to enhance protein refolding have the activity to accelerate the isomerization. To evaluate the effects of chemicals on the isomerization rate, we set up a new NMR (EXSY) method that is invulnerable to their inhibitory activity, if any, and to their large NMR signals. With this method, we found that dimethylbenzylammonium propane sulfonate (NDSB-256) increase the isomerization rate in a concentration-dependent manner for the first time. Acceleration by imidazole (suggested but not experimentally confirmed) was also demonstrated. Arginine, a most popular refolding additive, did not show any significant effects on the isomerization reaction as expected.

The role of biliary epithelial cells in the immunopathogenesis of non-suppurative destructive cholangitis in murine hepatic graft-versus-host disease.

Non-suppurative destructive cholangitis (NSDC) is characterized by T-cell infiltration of the biliary epithelia of small-to medium-caliber bile ducts, causing apoptosis of biliary epithelial cells (BEC) and, ultimately, ductopenia. NSDC is the primary histopathologic process in the autoimmune disease known as primary biliary cirrhosis (PBC) and in alloimmune graft-versus-host disease (GVHD) and hepatic allograft rejection. The onset of NSDC in the B10.D2→BALB/c murine model of hepatic GVHD is preceded by hepatic production of pro-inflammatory cytokines, accumulation of lipopolysaccharide (LPS), and expression of chemokine genes. To explain the curious restriction of NSDC to small- and medium-caliber intrahepatic bile ducts, we hypothesized that BEC lining these bile ducts secrete chemokines and cytokines that chemoattract, activate, and polarize the effector T cells mediating NSDC. To test this hypothesis we stimulated BALB/c immortalized BEC (IBEC) in vitro with pro-inflammatory mouse recombinant cytokines with and without LPS and determined the expression of chemokines and cytokines by IBEC using a polymerase chain reaction (PCR), quantitative protein enzyme-linked immunosorbent assays (ELISAs), and microarrays. The capacity of stimulated IBEC to chemoattract activated T cells was assessed in the presence and absence of inhibitors of specific chemokine receptors. We found that pro-inflammatory cytokines, especially the combination of IFNγ and TNFα, induced IBEC gene expression and the secretion of chemokine ligands for the chemokine receptors CCR1, CCR3, CCR5, and CXCR3. Chemokines secreted by IBEC stimulated with IFNγ plus TNFα chemoattracted activated T cells. Inhibition of CCR1, CCR3, CCR5, or CXCR3 significantly reduced the chemoattraction of activated T cells. We conclude that BEC probably play an active role in the immunopathogenesis of NSDC by mediating the chemoattraction and terminal activation of effector T cells responsible for apoptosis of BECs and ductopenia. Selective chemokine expression by BEC lining small- and medium-caliber bile ducts could explain the restriction of NSDC to ducts of this caliber. Inhibition of CCR1, CCR3, CCR5, and CXCR3 to block the chemoattraction and terminal activation of alloreactive T cells represents a potential therapeutic strategy for preventing NSDC after hematopoietic stem-cell transplantation or orthotopic liver transplantation.

Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein.

OBJECTIVES: We previously observed an association between ovarian cancer outcome and statin use and hypothesized lipoproteins have direct effects on ovarian cancer proliferation. Here we investigate the direct effects of low density lipoprotein (LDL) and oxidized LDL (oxLDL) on proliferation and the inhibitory effects of fluvastatin and a liver X receptor (LXR) agonist. METHODS: The effects of LDL, oxLDL, the LXR agonist TO901317, fluvastatin and cisplatin on cellular proliferation were determined using MTT assays. LXR pathway proteins were assayed by immunoblotting. Cytokine expression was determined by antibody array. RESULTS: Concentrations of oxLDL as small as 0.1 microg/ml stimulated CAOV3 and SKOV3 proliferation, while LDL had no effect. TO901317 inhibited the proliferation of CAOV3, OVCAR3 and SKOV3 cells stimulated by oxLDL. Fluvastatin inhibited oxLDL mediated proliferation of CAOV3 and SKOV3. Cardiotrophin 1 (CT-1) was mitogenic to CAOV3 and SKOV3, was induced by oxLDL, and was reversed by TO901317. OxLDL increased cisplatin IC50s by 3.8 microM and > 60 microM for CAOV3 and SKOV3 cells, respectively. The LXR pathway proteins CD36, LXR, and ABCA1 were expressed in eight ovarian carcinoma cell lines (A2780, CAOV3, CP70, CSOC882, ES2, OVCAR3, SKOV3). CONCLUSIONS: OxLDL reduced ovarian carcinoma cell chemosensitivity and stimulated proliferation. These effects were reversed by LXR agonist or fluvastatin. The LXR agonist also inhibited expression of the ovarian cancer mitogen CT-1. These observations suggest a biologic mechanism for our clinical finding that ovarian cancer survival is associated with statin use. Targeting LXR and statin use may have a therapeutic role in ovarian cancer.

Interaction of CD44 and hyaluronic acid enhances biliary epithelial proliferation in cholestatic livers.

Biliary epithelia express high levels of CD44 in hepatobiliary diseases. The role of CD44-hyaluronic acid interaction in biliary pathology, however, is unclear. A rat model of hepatic cholestasis induced by bile duct ligation was employed for characterization of hepatic CD44 expression and extracellular hyaluronan distribution. Cell culture experiments were employed to determine whether hyaluronan can regulate cholangiocyte growth through interacting with adhesion molecule CD44. Biliary epithelial cells were found to express the highest level of CD44 mRNA among four major types of nonparenchymal liver cells, including Kupffer, hepatic stellate, and liver sinusoidal endothelial cells isolated from cholestatic livers. CD44-positive biliary epithelia lining the intrahepatic bile ducts were geographically associated with extracellular hyaluronan accumulated in the portal tracts of the livers, suggesting a role for CD44 and hyaluronan in the development of biliary proliferation. Cellular proliferation assays demonstrated that cholangiocyte propagation was accelerated by hyaluronan treatment and antagonized by small interfering RNA CD44 or anti-CD44 antibody. The study provides compelling evidence to suggest that proliferative biliary epithelia lining the intrahepatic bile ducts are a prime source of hepatic CD44. CD44-hyaluronan interaction, by enhancing biliary proliferation, may play a pathogenic role in the development of cholestatic liver diseases.

Synthesis of well-defined poly(N-isopropylacrylamide)-b-poly(L-glutamic acid) by a versatile approach and micellization.

A novel Fmoc-protected chain transfer agent (CTA) was synthesized and applied in the reversible addition-fragmentation chain transfer (RAFT) polymerization of N-isopropylacrylamide (NIPAAm), resulting in well-defined Fmoc-protected PNIPAAm and the amino-end capped PNIPAAm by the subsequent hydrolysis. Poly(N-isopropylacrylamide)-b-poly(l-glutamic acid) (PNIPAAm-b-PLGA) with controlled molecular weight and narrow molecular weight distribution was synthesized successfully via ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydrides (NCAs) by using PNIPAAm-NH2 as the macroinitiator. Both pH- and thermo-responsive micellization behaviors of the block copolymer PNIPAAm55-b-PLGA35 in dilute aqueous solution were investigated by means of the pyrene fluorescence, circular dichroism, 1H NMR, transmission electron microscopy and dynamic and static light scattering. Spherical PLGA-core and rod-like PNIPAAm-core micelles are formed in response to pH and temperature. The reversible transition between the PLGA-core and PNIPAAm-core micelles was observed. This work provides a versatile approach for synthesizing well-defined stimuli-responsive polypeptide-based double hydrophilic diblock copolymers (DHBCs), and is of great potential for generating useful stimuli-responsive materials in biomedical applications.