Super enhancer related gene ANP32B promotes the proliferation of acute myeloid leukemia by enhancing MYC through histone acetylation.

BACKGROUND: Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, and childhood AML accounts for about 20% of pediatric leukemia. ANP32B, an important nuclear protein associated with proliferation, has been found to regulate hematopoiesis and CML leukemogenesis by inhibiting p53 activity. However, recent study suggests that ANP32B exerts a suppressive effect on B-cell acute lymphoblastic leukemia (ALL) in mice by activating PU.1. Nevertheless, the precise underlying mechanism of ANP32B in AML remains elusive. RESULTS: Super enhancer related gene ANP32B was significantly upregulated in AML patients. The expression of ANP32B exhibited a negative correlation with overall survival. Knocking down ANP32B suppressed the proliferation of AML cell lines MV4-11 and Kasumi-1, along with downregulation of C-MYC expression. Additionally, it led to a significant decrease in H3K27ac levels in AML cell lines. In vivo experiments further demonstrated that ANP32B knockdown effectively inhibited tumor growth. CONCLUSIONS: ANP32B plays a significant role in promoting tumor proliferation in AML. The downregulation of ANP32B induces cell cycle arrest and promotes apoptosis in AML cell lines. Mechanistic analysis suggests that ANP32B may epigenetically regulate the expression of MYC through histone H3K27 acetylation. ANP32B could serve as a prognostic biomarker and potential therapeutic target for AML patients.

The clinical value of combining shear wave elastography, VOCAL technique, and T2* MRI of early gestation placenta to predict pre-eclampsia.

OBJECTIVE: To investigate the clinical value of combining shear wave elastography (SWE) with the Volumetric Organ Computer-Aided AnaLysis (VOCAL) technique and T2* magnetic resonance imaging (MRI) to predict pre-eclampsia (PE). METHODS: From December 2022 to March 2023, we recruited 31 pregnant women diagnosed with PE at our hospital as the observation group and 85 normal pregnant women as the control group. Differences in placental elasticity, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and T2* MRI perfusion fraction (f) were compared between the two groups. Received operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of placental elasticity, VI, FI, VFI, f, and their combination for predicting PE. RESULTS: Placental elasticity was higher in the observation group than in the control group, while VI, FI, VFI, and f were lower in the observation group (all p < 0.05). The area under the curve (AUC) for placental elasticity, VI, FI, VFI, f, and their combination for predicting PE were 0.85, 0.77, 0.78, 0.84, 0.65, and 0.94, respectively. The sensitivity was 71%, 55%, 94%, 65%, 55%, and 81%. The specificity was 92%, 91%, 60%, 92%, 79%, and 98%. The combined prediction model had a higher AUC than the individual predictors (p < 0.05). CONCLUSION: SWE combined with VOCAL technique and T2* MRI has high value for predicting PE and can provide reference information for clinical diagnosis.

Conjunctival sac flora and drug susceptibility analysis in normal children in East China.

PURPOSE: To investigate the distribution characteristics of conjunctival sac flora and assess the susceptibility of commonly used topical antimicrobial agents in normal children under the age of 18 in East China. METHODS: In 2019, a study was conducted at Qingdao Eye Hospital of Shandong First Medical University to analyze the microorganism cultures of conjunctival sac in 1258 normal children (2516 eyes; average age, 6.21 ± 3.78 years) in East China. Exclusion criteria included children with ocular surface diseases and those who had used any topical antimicrobial agents recently. The microorganism species in the conjunctival sac were analyzed using the M-38A protocol (microdilution method; investigators read the minimum inhibitory concentration [MIC] values) by the Clinical and Laboratory Standards Institute to determine drug susceptibility. RESULTS: The incidence of conjunctival sac microorganism in children was 32.87% (827/2516), a total of 541 cases (male 293, female 248). Children with conjunctival sac flora in a single eye were 255 and in both eyes were 286 (no statistical difference, P > 0.05). The concordance rate of children with binocular conjunctival sac flora was 32.16% (174/541; male 84, female 90). A total of 42 species of bacteria were detected. Children with Gram-positive cocci accounted for the highest proportion, 91.54% (757/827). The top three bacteria with the highest detection rates were Staphylococcus epidermidis (S. epidermidis; 52.12%), Streptococcus (12.09%), and Staphylococcus aureus (S. aureus; 10.76%). Streptococcus mitis (5.20%) accounted for the highest proportion of Streptococcus.S. epidermidis had the highest proportion in all age groups and was positively correlated with age (r = 0.89, P = 0.03). Before six years of age, the streptococcal proportion(mainly S. mitis) was greater than that of Staphylococcus aureus. The drug susceptibility analysis showed that S. epidermidis was most sensitive to gatifloxacin (98.61%), while it had the highest resistance rate to erythrocin (87.94%). S. aureus had the highest susceptibility to moxifloxacin (100%). Streptococcus was most sensitive to moxifloxacin (96.97%) and had the highest resistance rate to tobramycin (92.93%). CONCLUSIONS: Conjunctival sac flora in children was dominated by Gram-positive cocci, mainly S. epidermidis, S. aureus, and Streptococcus. S. epidermidis increased with age; the proportion of Streptococcus was higher than S. aureus among children aged 0-6 years. The typical conjunctiva sac flora was generally sensitive to quinolones, such as moxifloxacin and gatifloxacin; Streptococcus displayed high resistance to tobramycin antibiotics; and the female children had higher resistance to tobramycin than the male children.

Understanding the wetting discrepancy in calcium alumino silicate hydrate induced by Al/Si ratio.

The application of supplementary cementitious materials (SCMs) in concrete can improve its durability in the marine environment. Calcium alumino silicate hydrate (CASH) is the main hydration product of SCMs; however, to date, the mechanism of the wetting discrepancy in CASH with different Al/Si ratios has not been revealed at the molecular scale. Herein, the molecular dynamics simulation method was used to study the wettability of water nanodroplets on the surface of CASH substrates with different Al/Si ratios, aiming to reveal the influence of CASH gel with different Al contents on the wettability of water molecules. The simulation results suggested that the CASH interface with a high Al/Si ratio has better wettability for nanodroplets. The microcosmic analysis showed that the interaction between particles and the CASH substrate is affected by the Al content. The electronegativity of the CASH substrate increases due to the substitution of Al-O tetrahedrons, which makes it stronger to solidify Ca ions on its surface and easier to form hydrogen bonds with water molecules in a nanodroplet. The orientation distribution of water molecules further revealed the source of the force of the CASH substrate on nanodroplets at the atomic level. The analysis of the dynamic properties showed that the H-bonds between CASH substrate with a high Al/Si ratio and water molecules are more stable, and thus the nanodroplets have better stability on the surface of CASH.

A retrospective survey of strabismus surgery in a tertiary eye center in northern China, 2014-2019.

BACKGROUND: To evaluate the distribution pattern and changes of strabismus surgery in northern China. METHODS: The records of strabismus patients at Qingdao Eye Hospital from January 2014 to December 2019 were reviewed retrospectively. The characteristics analyzed included gender, regional distribution, constituent ratio of age and type of strabismus. Changes during the periods 2014-2016 and 2017-2019 were compared and analyzed. RESULTS: A total of 5746 strabismus patients were recruited. The number of strabismus patients was relatively stable each year from 2014 to 2016 but gradually increased each year from 2017 to 2019. Of these, 51.7% (2968/5746) were male, and 48.3% (2778/5746) were female. The majority (89.8%, 5159/5746) of the patients were from Shandong Province. The statistical results of the constituent ratio of age showed that 32.4% (1860/5746) were 7-12 years old (primary school level). Patients under 12 years of age (preschool and primary school level) accounted for 60.0% (3447/5746) of all the patients. In terms of the types of strabismus, exotropia accounted for 63.5% (3650/5746), followed by esotropia and vertical rotational strabismus at 13.2% (758/5746) and 9.7% (555/5746), respectively. Intermittent exotropia was the most common type among the exotropia patients, accounting for 71.3% (2604/3650). Among the patients with intermittent exotropia, 62.5% (1627/2604) were children aged 4-12 years, and the basic type of intermittent exotropia was the main type. Four percent (231/5746) of the patients, of which adult patients comprised the main population, required reoperation. CONCLUSIONS: Patients with strabismus at primary school level comprised the largest group of strabismus patients in north China. Exotropia was the most common type of strabismus, and intermittent exotropia was the most common type of exotropia. The rate of exotropia to esotropia was 5:1.

Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression.

Homozygous tau knockout (Mapt-/-) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau in maintaining the survival of midbrain dopaminergic neurons (mDANs) during aging. However, it remains to be determined whether the microtubule-associated protein tau regulates the differentiation and survival of mDANs during embryonic developmental stages. Here, we show that tau haploinsufficiency in postnatal day 0 (P0) heterozygous (Mapt+/-) pups, but not a complete loss of tau in the Mapt-/- littermates, led to a significant reduction of DA neurons in the VTA. This selective loss of DA neurons correlated with a similar reduction in orthodenticle homeobox 2 (Otx2), which is restricted to VTA neurons at the postmitotic stage and selectively controls the neurogenesis and survival of specific neuronal subtypes of VTA. Moreover, the prenatal developmental cell death in the Mapt+/- VTA specifically increased, and the expression of microtubule-associated protein (MAP)-1A was significantly up-regulated in the P0 Mapt-/- , but not the Mapt+/- , pups. These results suggest that tau haploinsufficiency, without the compensation effect of MAP1A, induces reduction of Otx2 expression, increases prenatal cell death, and accordingly leads to selective loss of VTA DA neurons in the early postnatal stage. Our findings highlight the impact of tau haploinsufficiency on the survival of mDANs and indicate that tau may participate in midbrain development in a dose-dependent way.-Zheng, M., Jiao, L., Tang, X., Xiang, X., Wan, X., Yan, Y., Li, X., Zhang, G., Li, Y., Jiang, B., Cai, H., Lin, X. Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression.

Chloride Transport and Related Influencing Factors of Alkali-Activated Materials: A Review.

Chloride transport is a vital issue in the research on the durability of alkali-activated materials (AAMs). Nevertheless, due to its miscellaneous types, complex mix proportions, and limitations in testing methods, the reports of different studies are numerous and vary greatly. Therefore, in order to promote the application and development of AAMs in chloride environments, this work systematically reviews the chloride transport behavior and mechanism, solidification of chloride, influencing factors, and test method of chloride transport of AAMs, along with conclusions regarding instructive insights to the chloride transport problem of AAMs in future work.

Unilateral chronic angle-closure glaucoma in a pediatric patient with neurofibromatosis: a case report.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease that causes multi-system damage. It is rarely associated with angle-closure glaucoma, especially in pediatric patients. We herein report a case of unilateral chronic angle-closure glaucoma in a patient with NF1. A 5-year-old girl with a large subcutaneous soft mass and multiple scattered coffee-milk spots presented with low vision, increased intraocular pressure, and angle closure in her right eye. Lisch nodules were seen in both eyes. In her right eye, ectropion uveae was observed at the top and bottom margins of the pupil. Magnetic resonance imaging of the skull and orbit revealed no abnormalities. Finally, trabeculectomy was performed on the right eye, after which the right eye showed a stable intraocular pressure. NF1 combined with angle-closure glaucoma is rare and easily missed in the clinical setting. Early diagnosis and treatment may achieve good results.

BRD4 PROTAC degrader MZ1 exhibits anti-B-cell acute lymphoblastic leukemia effects via targeting CCND3.

INTRODUCTION: B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent malignant tumor affecting children. While the majority of B-ALL patients (90%) experience successful recovery, early relapse cases of B-ALL continue to exhibit high mortality rates. MZ1, a novel inhibitor of Bromodomains and extra-terminal (BET) proteins, has demonstrated potent antitumor activity against hematological malignancies. The objective of this study was to examine the role and therapeutic potential of MZ1 in the treatment of B-ALL. METHODS: In order to ascertain the fundamental mechanism of MZ1, a sequence of in vitro assays was conducted on B-ALL cell lines, encompassing Cell Counting Kit 8 (CCK8) assay, Propidium iodide (PI) staining, and Annexin V/PI staining. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to examine protein and mRNA expression levels. Transcriptomic RNA sequencing (RNA-seq) was utilized to screen the target genes of MZ1, and lentiviral transfection was employed to establish stably-expressing/knockdown cell lines. RESULTS: MZ1 has been observed to induce the degradation of Bromodomain Containing 4 (BRD4), Bromodomain Containing 3 (BRD3), and Bromodomain Containing 2 (BRD2) in B-ALL cell strains, leading to inhibited cell growth and induction of cell apoptosis and cycle arrest in vitro. These findings suggest that MZ1 exhibits cytotoxic effects on two distinct molecular subtypes of B-ALL, namely 697 (TCF3/PBX1) and RS4;11 (MLL-AF4) B-ALL cell lines. Additionally, RNA-sequencing analysis revealed that MZ1 significantly downregulated the expression of Cyclin D3 (CCND3) gene in B-ALL cell lines, which in turn promoted cell apoptosis, blocked cell cycle, and caused cell proliferation inhibition. CONCLUSION: Our results suggest that MZ1 has potential anti-B-ALL effects and might be a novel therapeutic target.

Hydrogen sulfide prevents hypoxia-induced apoptosis via inhibition of an H2O2-activated calcium signaling pathway in mouse hippocampal neurons.

Hydrogen sulfide (H(2)S), an endogenous gaseous mediator, has been shown to exert protective effects against damage to different organs in the human body caused by various stimuli. However, the potential effects of H(2)S on hypoxia-induced neuronal apoptosis and its mechanisms remain unclear. Here, we exposed mouse hippocampal neurons to hypoxic conditions (2% O(2), 5% CO(2) and 93% N(2) at 37 °C) to establish a hypoxic cell model. We found that 4-h hypoxia treatment significantly increased intracellular reactive oxygen species (ROS) levels, and pretreatment with NaHS (a source of H(2)S) for 30 min suppressed hypoxia-induced intracellular ROS elevation. The hypoxia treatment significantly increased cytosolic calcium ([Ca(2+)](i)), and pretreatment with NaHS prevented the increase in [Ca(2+)](i). Additionally, polyethylene glycol (PEG)-catalase (a H(2)O(2) scavenger) but not PEG-SOD (an O(2)(-) scavenger) conferred an inhibitory effect similar to H(2)S on the hypoxia-induced increase in [Ca(2+)](i). Furthermore, we found that pretreatment with NaHS could significantly inhibit hypoxia-induced neuronal apoptosis, which was also inhibited by PEG-catalase or the inositol 1,4,5-triphosphate (IP(3)) receptor blocker xestospongin C. Taken together, these findings suggest that H(2)S inhibits hypoxia-induced apoptosis through inhibition of a ROS (mainly H(2)O(2))-activated Ca(2+) signaling pathway in mouse hippocampal neurons.

BRD4 PROTAC degrader MZ1 exerts anticancer effects in acute myeloid leukemia by targeting c-Myc and ANP32B genes.

Acute myeloid leukemia (AML) is a highly cancerous and aggressive hematologic disease with elevated levels of drug resistance and relapse resulting in high mortality. Recently, bromodomains and extra-terminal (BET) protein inhibitors have been extensively researched in hematological tumors as potential anticancer agents. MZ1 is a novel BET inhibitor that mediates selective proteins degradation and suppression of tumor growth through proteolysis-targeting chimeras (PROTAC) technology. Accordingly, this study aimed to investigate the role and therapeutic potential of MZ1 in AML. In this study, we first identified that AML patients with high BRD4 expression had poor overall survival than those with low expression group. MZ1 inhibited AML cell growth and induced apoptosis and cycle arrest in vitro. MZ1 induced degradation of BRD4, BRD3 and BRD2 in AML cell strains. Additionally, MZ1 also initiated the cleavage of poly-ADP-ribose polymerase (PARP), which showed cytotoxic effects on NB4 (PML-RARa), K562 (BCR-ABL), Kasumi-1 (AML1-ETO), and MV4-11 (MLL-AF4) cell lines representing different molecular subtypes of AML. In AML mouse leukemia model, MZ1 significantly decreased leukemia cell growth and increased the mouse survival time. According to the RNA-sequencing analysis, MZ1 led to c-Myc and ANP32B genes significant downregulation in AML cell lines. Knockdown of ANP32B promoted AML cell apoptosis and inhibited cell growth. Overall, our data indicated that MZ1 had broad anti-cancer effects on AML cell lines with different molecular lesions, which might be exploited as a novel therapeutic strategy for AML patients.

The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.

Autophagy-mediated chemosensitization by cysteamine in cancer cells.

Cysteamine (CS) has many biomedical and clinical applications because of its excellent water solubility, low cytotoxicity and good biocompatibility. A previous study by Brawer et al. reported the occurrence of many Gomori inclusion bodies in CS-treated astrocytes, which would suggest the induction of autophagy. Here we provided a comprehensive line of evidence demonstrating that CS caused autophagosome accumulation in cancer cells. CS exerted a biphasic effect on the autophagy process, increasing the formation of autophagosomes in the early phase and blocking the autophagic degradation in a later phase. Furthermore, we showed that CS sensitized doxorubicin-elicited chemotherapeutic killing in HeLa, B16 melanoma and doxorubicin-resistant MCF-7 cells and also enhanced chemotherapeutic efficacy of doxorubicin in a mouse melanoma model. Finally, we demonstrated that the chemosensitizing effect of CS was at least partly dependent on its ability to modulate autophagy. Our results revealed a novel biological function for CS in enhancing the chemotherapeutic effect of doxorubicin through autophagy modulation and pointed to the potential use of CS in adjunct cancer chemotherapy.

Full-Diffractive Multifocal Intraocular Lens Posterior Optic Capture for Selected Pediatric Cataracts.

PURPOSE: To evaluate the short-term outcomes of implantation of a full-diffractive multifocal intraocular lens (IOL) with optic capture for selected pediatric cataracts. METHODS: In this prospective study, patients with pediatric cataract aged 3 to 14 years were selected to receive multifocal IOL (Tecnis ZMB00; Abbott Medical Optics) posterior optic capture. Visual acuity, stereopsis, visual quality, and complications were assessed. RESULTS: Forty-five patients (66 eyes) were recruited with a follow-up of 9.09 ± 5.93 months (range: 6 to 24 months). The cataract was bilateral in 21 patients and unilateral in 24 patients. At the last follow-up visit, the mean distance-corrected distance, intermediate, and near visual acuity was 0.28 ± 0.25, 0.43 ± 0.24, and 0.39 ± 0.27 logMAR, respectively. Among the patients with bilateral cataract, postoperative corrected distance visual acuity (CDVA) was 20/40 or better in 79% (33 of 42) of the eyes and 20/20 in 26% (11 of 42) of the eyes. Of the patients with unilateral cataract, 54% (13 of 24) achieved a CDVA of 20/40 or better but none obtained a CDVA of 20/20. All patients developed stereopsis postoperatively (P < .05). There was no significant difference in modulation transfer function cut-off and Strehl ratio between the eyes with a multifocal IOL and the healthy eyes of patients with unilateral cataract (P > .05). Objective Scatter Index values were significantly better in the healthy eyes (P < .05). No posterior capsule opacification, posterior synechiae, secondary glaucoma, pigmentary IOL deposits, or IOL decentration was observed during the follow-up period. CONCLUSIONS: Short-term follow-up results suggest full-diffractive multifocal IOL optic capture may benefit appropriately selected patients with pediatric cataract. [J Refract Surg. 2021:37(6):390-397.].

Cataract surgery contributes to ocular axis growth of aphakic eyes in infants with complex microphthalmos.

To observe the ocular axis, visual acuity and intraocular pressure (IOP) of aphakic eye in infants with congenital cataract and complex microphthalmos after first-stage cataract surgery.This retrospective study included infants with congenital cataract and operated at the Qingdao Eye Hospital between January 2010 and December 2014. The infants were divided into 2 groups: preoperative axial length <18 mm (microphthalmos) or ≥18 mm (controls). Follow-up lasted 24 months; visual acuity, axial length, and IOP were evaluated.There were 28 infants (55 eyes) in the microphthalmos group and 35 (61 eyes) in the control group. The preoperative visual acuity was negative for optokinetic nystagmus, while the postoperative visual acuity was positive for optokinetic nystagmus in both groups. The growth rate was higher in the microphthalmos group (1.4 ±â€Š0.8 vs 0.8 ±â€Š0.4 mm/yr, P < .001 vs controls). The axial length was smaller in the microphthalmos group at all time points compared with the control group (all P < .001). There was no changes in IOP in the microphthalmos group from baseline to 24 months (P = .147), but the IOP was slightly decreased in the control group (P = .015).Cataract surgery may contribute to ocular axis growth in infants with complex microphthalmos.

The effects of simultaneous operation on dissociated vertical deviation with horizontal and torsional strabismus.

AIM: To investigate the therapeutic effects of simultaneous horizontal and vertical operations on dissociated vertical deviation (DVD) associated with other deviations. METHODS: Forty-five cases of DVD with horizontal and torsional strabismus underwent combined operation were collected retrospectively. All clinical records were analyzed. All patients were followed up for 6 to 24mo. Wilcoxon signed-ranks test was performed to evaluate the changes of vertical and horizontal deviation. χ 2 test was used to evaluate the changes of binocular visual function. RESULTS: Forty-five cases included 36 patients with intermittent exotropia and binocular inferior oblique overaction (IOOA), 5 patients with concomitant esotropia and binocular IOOA, 4 patients with intermittent exotropia and monocular superior oblique palsy. The superior rectus recession (SRR) combined with horizontal rectus recession and the myectomy of inferior oblique or anterior transposition were operated simultaneously to correct all types of strabismus. There were 43 cases who achieved normal eye position in vertical direction, while 2 cases were with undercorrection of 5Δ to 6Δ. In patients with horizontal strabismus, 2 cases of exotropia were with overcorrection of 6Δ to 8Δ, 1 case of esotropia was with undercorrection of 6Δ, and 1 case of monocular superior oblique palsy with compensatory head posture was not significantly improved. The binocular visual function of most patients recovered after operation. The difference of the binocular visual function and eye position were significant compared with that before operation (P<0.05). CONCLUSION: The simultaneous operation on DVD with horizontal and torsional strabismus is successful.

Lacrimal androgen-binding proteins protect against Aspergillus fumigatus keratitis in mice.

AIM: To clarify the regulatory mechanisms of lacrimal androgen-binding proteins (ABPs) in mice with keratitis caused by Aspergillus fumigatus (A. fumigatus). METHODS: Mouse models of A. fumigatus keratitis were established. Lacrimal glands were removed after 24 h for general and histological comparison. Lacrimal ABPs were detected by qRT-PCR and quantitative proteomic analysis, or were detected by qRT-PCR after subconjunctival or lacrimal gland injection with dexamethasone. Unique inflammatory factors were detected by qRT-PCR, Western blot and/or immunofluorescence. Interleukin-1ß (IL-1ß) was injected into the lacrimal gland to explore the relationship between IL-1ß and lacrimal ABPs. RESULTS: The lacrimal glands of mice with fungal keratitis were larger than normal mice and these structures became disorganized. Moreover, the expression of ABP ε and ABP δ were increased. Subconjunctival injection with dexamethasone could reduce the size of the lacrimal gland and increase the expression of ABP ε and ABP δ, while lacrimal gland injection with dexamethasone had no obvious effects. The expression of IL-1ß in the lacrimal gland of mice with A. fumigatus keratitis was increased. When IL-1ß was injected into the lacrimal gland, the lacrimal gland enlarged and the expression of ABP ε and ABP δ decreased. CONCLUSION: Lacrimal glands contributed to protection in fungal keratitis, which was not due to the involvement of inflammatory cells in mice. ABP δ and ABP ε of mice were involved in reducing the severity of corneal damage in mice with A. fumigatus keratitis. Moreover, the expression of IL-1ß and ABP δ and ABP ε were intrinsically linked.

Identification of nose-to-brain homing peptide through phage display.

Brain delivery of drug molecules through the nasal passage represents a viable approach for bypassing the blood-brain barrier (BBB) but remains a major challenge due to lack of efficient homing carriers. To screen for potential peptides with the ability to transport into the brain via the nasal passage, we applied a C7C phage peptide display library (Ph.D.-C7C) intra-nasally to anesthetized rats and recovered phage from the brain tissue 45 min after phage administration. After three rounds of panning, 10 positive phage clones were selected and sequenced. Clone7, which exhibited highest translocation efficiency, was chosen for further studies. After nasal administration, Clone7 entered the brain within 30 min and exhibited translocation efficiency about 50-fold higher than a random phage. A 11-amino acid synthetic peptide derived from the displayed sequence of Clone7 (ACTTPHAWLCG) efficiently inhibited the nasal-brain translocation of Clone7. Both phage recovery results and fluorescent microscopy images revealed the presence of many more Clone7 phage in the brain than in the liver, kidney and other internal organs after the nasal administration, suggesting that Clone7 bypassed the BBB and entered brain directly. Furthermore, both Clone7 and the ACTTPHAWLCG peptide were found to be heavily distributed along the olfactory nerve after the nasal administration, further suggesting a direct passage route into the brain via the olfactory region. These results demonstrated the feasibility of using the in vivo phage display approach for selecting peptides with the nose-to-brain homing capability and may have implications for the development of novel targeting carriers useful for brain delivery.

Tau Deficiency Down-Regulated Transcription Factor Orthodenticle Homeobox 2 Expression in the Dopaminergic Neurons in Ventral Tegmental Area and Caused No Obvious Motor Deficits in Mice.

Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes is controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+, tau+/-, tau-/- mice. We found tau deficiency could not induce significant motor disorders. However, we discovered lower expression levels of transcription factors Orthodenticle homeobox 2 (OTX2) of mDANs in older aged mice. Compared with age-matched tau+/+ mice, there were 54.1% lower (p = 0.0192) OTX2 protein (OTX2-fluorescence intensity) in VTA DA neurons of tau+/- mice and 43.6% lower (p = 0.0249) OTX2 protein in VTA DA neurons of tau-/- mice at 18 months old. Combined with the relevant reports, our results suggested that tau deficiency alone might not be enough to mimic the pathology of Parkinson's disease. However, OTX2 down-regulation indicates that mDANs of tau-deficient mice will be more sensitive to toxic damage from MPTP.

Immobilization of Candida antarctic lipase B on MWNTs modified by ionic liquids with different functional groups.

Multiwalled carbon nanotubes (MWNTs) were modified by imidazole-based ionic liquids with different kinds of functional groups such as alkyl, carboxyl, amino and hydroxyl. The supports were used to immobilize Candida antarctic lipase B (CALB) and the influence of different functional groups of ionic liquids on enzymatic properties was investigated by the hydrolysis reaction of triacetin. The results revealed that the functionalization process did not destroy the structural integrity of MWNTs, and the enzymatic properities of CALB which immobilized on the MWNTs modified by ionic liquids with different kinds of functional groups were all improved. The hydroxyl functionalized ionic liquids which exhibited the best enzymatic properities was selected to investigate the effects of different carbon chain length on the enzymatic properties of immobilized CALB. Among them, CALB which immobilized on MWNTs modified by hydroxyl functionalized ionic liquid with suitable chain length (MWNTs-IL(8C)-OH-CALB) had the highest specific activity, with a specific activity of 18.11 times that of MWNTs-CALB. Furthermore, it also presented best thermal stability and reusability. The residual activity of MWNTs-IL(8C)-OH-CALB held over 64.01% of the initial activity after being incubated for 20min at 70°C, and the residual activity was 85.56% after 4 cycles of use.