Engrailed: Pathological and physiological effects of a multifunctional developmental gene.

Engrailed-1 (EN1) is a developmental gene that encodes En1, a highly conserved transcription factor involved in regionalization during early embryogenesis and in the later maintenance of normal neurons. After birth, EN1 still plays a role in the development and physiology of the body; for example, it exerts a protective effect on midbrain dopaminergic (mDA) neurons, and loss of EN1 causes mDA neurons in the ventral midbrain to gradually die approximately 6 weeks after birth, resulting in motor and nonmotor symptoms similar to those observed in Parkinson's disease. Notably, EN1 has been identified as a possible susceptibility gene for idiopathic Parkinson's disease in humans. EN1 is involved in the processes of wound-healing scar production and tissue and organ fibrosis. Additionally, EN1 can lead to tumorigenesis and thus provides a target for the treatment of some tumors. In this review, we summarize the effects of EN1 on embryonic organ development, describe the consequences of the deletion or overexpression of the EN1 gene, and discuss the pathways in which EN1 is involved. We hope to clarify the role of EN1 as a developmental gene and present potential therapeutic targets for diseases involving the EN1 gene.

Mesoionic Carbene-Catalyzed Formyl Alkylation of Aldehydes.

Ketones are among the most useful functional groups in organic synthesis, and they are commonly encountered in a broad range of compounds with various applications. Herein, we describe the mesoionic carbene-catalyzed coupling reaction of aldehydes with non-activated secondary and even primary alkyl halides. This metal-free method utilizes deprotonated Breslow intermediates derived from mesoionic carbenes (MICs), which act as super electron donors and induce the single-electron reduction of alkyl halides. This mild coupling reaction has a broad substrate scope and tolerates many functional groups, which allows to prepare a diversity of simple ketones as well as bio-active molecules by late-stage functionalization.

Base-Catalyzed H/D Exchange Reaction of Difluoromethylarenes.

The budding deuteriodifluoromethyl group (CF2D) is a potentially significant functional group in medicinal chemistry. Herein, we investigated t-BuOK-catalyzed H/D exchange reaction of difluoromethylarenes in DMSO-d6 solution. The method provides excellent deuterium incorporation at the difluoromethyl group. Meanwhile, the effect of a trace amount of D2O in DMSO-d6 solution on the deuteration reaction was also investigated.

Synthesis, Structure, and Photophysical Properties of m-Phenylene-Embedded Cycloparaphenylene Nanorings.

Five m-phenylene-embedded cycloparaphenylenes m3[9]CPP 1-5 were synthesized by the platinum-mediated cyclooligomerization strategy with high overall yields. The structures of m3[9]CPP 1-3 were determined by X-ray diffraction analysis. Compared to [9]CPP, m3[9]CPP 1 caused a significant blueshift in the UV-vis absorption and fluorescence spectra. This result shows that the radial π-conjugation is distorted and partially interrupted. The photophysical properties of m3[9]CPP 1 were further tuned by the introduction of various substituents for m3[9]CPP 2-5. Methoxy group substitution at m-phenylene did not change the photophysical properties significantly. Replacement of m-phenylene by tetrafluoro-m-phenylene achieved a significant blueshift. When the carboxyl group was embedded at m-phenylene or the methoxy group was embedded at p-phenylene, significant redshifts were observed with blue color emission. Theoretical calculations revealed that the decrease in the HOMO-LUMO gap in m3[9]CPP 4 and 5 is favorable for the redshift of the fluorescence spectrum.

[The prevalence and influencing factors of eye diseases for IT industry video operation workers].

OBJECTIVE: To investigate the situation of video-contact and eye diseases for IT industry video operation workers, and to analyze the influencing factors, providing scientific evidence for the make of health-strategy for IT industry video operation workers. METHODS: We take the random cluster sampling method to choose 190 IT industry video operation workers in a city of Jiangsu province, analyzing the relations between video contact and eye diseases. RESULTS: The daily video contact time of IT industry video operation workers is 6.0-16.0 hours, whose mean value is (I 0.1 ± 1.8) hours. 79.5% of workers in this survey wear myopic lens, 35.8% of workers have a rest during their working, and 14.2% of IT workers use protective products when they feel unwell of their eyes. Following the BUT experiment, 54.7% of IT workers have the normal examine results of hinoculus, while 45.3% have the abnormal results of at least one eye. Simultaneously, 54.7% workers have the normal examine results of hinoculus in the SIT experiment, however, 42.1% workers are abnormal. According to the broad linear model, there are six influencing factors (daily mean time to video, distance between eye and displayer, the frequency of rest, whether to use protective products when they feel unwell of their eyes, the type of dis player and daily time watching TV.) have significant influence on vision, having statistical significance. At the same time, there are also six influencing factors (whether have a rest regularly,sex, the situation of diaphaneity for cornea, the shape of pupil, family history and whether to use protective products when they feel unwell of their eyes.) have significant influence on the results of BUT experiment,having statistical significance. However, there are seven influencing factors (the type of computer, sex, the shape of pupil, the situation of diaphaneity for cornea, the angle between displayer and workers' sight, the type of displayer and the height of operating floor.) have significant influence on the results of SIT experiment,having statistical significance. CONCLUSIONS: The health-situation of IT industry video operation workers' eye is not optimistic, most of workers are lack of protection awareness; we need to strengthen propaganda and education according to its influencing factors and to improve the level of medical control and prevention for eye diseases in relevant industries.

Nanophthalmos: An Update on the Biological Parameters and Fundus Abnormalities.

Nanophthalmos is a clinical phenotype of simple microphthalmos, in which the anterior and posterior segments of the eyeball do not develop into a normal size without other major ocular or systemic anomalies. Typical clinical manifestations of nanophthalmos include short axial length, thickened sclera, small cornea, shallow anterior chamber, and increased lens-to-eye volume ratio. Currently, there is a lack of recognized diagnostic criteria for nanophthalmos. With the development of eye examination technologies, such as biological measurement and imaging examination, visualization and quantification of the eyeball's shape and structure in nanophthalmos can be realized. New clinical features have been reported, which are of great significance for diagnosing and treating nanophthalmos. This review introduces the related concepts of nanophthalmos and the new developments in its clinical characterization.

Ortho-Selective Hydrogen Isotope Exchange of Phenols and Benzyl Alcohols by Mesoionic Carbene-Iridium Catalyst.

Hydrogen isotope exchange reactions of phenols and benzyl alcohols have been achieved by a mesoionic carbene-iridium catalyst with high ortho selectivity and high functional group tolerance. Control experiments indicated that acetate is crucial to realize the ortho selectivity, whereas density functional theory calculations supported an outer-sphere direction with hydrogen bonding between acetate and the hydroxyl group.

Highly Enantioselective Synthesis of Pyrroloindolones and Pyrroloquinolinones via an N-Heterocyclic Carbene-Catalyzed Cascade Reaction.

In this work, the NHC-catalyzed Michael/Mannich/lactamization cascade reaction of enals with either indole-2-carboxaldehyde-derived aldimines or indole-7-carboxaldehyde-derived aldimines is described. This protocol enables the rapid assembly of optically active pyrroloindolones and pyrroloquinolinones derivatives under mild conditions with high yields, excellent enantioselectivities, and a broad substrate scope.

[Early-middle stage effect of percutaneous spinal endoscopic BEIS technique for lumbar spinal stenosis].

OBJECTIVE: To explore the clinical early-middle stage clinical effect of percutaneous spinal endoscopic with the technique of Broad Easy Immediate Surgery(BEIS) for lumbar spinal stenosis. METHODS: The clinical data of 57 patients with lumbar spinal stenosis treated by surgery from June 2015 to June 2016 were retrospectively analyzed, including 32 cases treated by percutaneous spinal endoscopic with the technique of BEIS (minimally invasive group) and 25 cases by posterior approach of lumbar pedicle screws internal fixation and intervertebral disc excision with bone graft fusion surgery (open surgery group). The pre-operative general data such as age, Body Mass Index (BMI) and etc. were analysed and compared. The operation time, intraoperative blood loss, hospitalization time of the two groups were analyzed. Visual analogue score(VAS), Oswestry Disability Index(ODI), Japanese Orthopedic Association Score(JOA) of preoperative and at 1 week, 1 month, 3 months, 6 months after surgery were used to evaluate the clinical outcome of the two group. RESULTS: All the operations were successful and all the patients recovered smoothly without severe complications, all the wounds got good healing. The pain of the lumbar and lower limb had been improved after surgery. All the patients were followed up more than 6 months with an average of(10.65±3.38) months. There was no significant difference in general data such as age, BMI, and etc. between two groups(P>0.05). There were significant differences in VAS, ODI between two groups at 1 week, 1, 3, 6 months after surgery(P<0.05). The postoperative lumbar pain of the minimally invasive group had been better improved than the open surgery group. However, there was no significant difference in JOA between two groups at 1 week, 1, 3, 6 months after surgery(P>0.05). Intraoperative blood loss and hospitalization time of minimally invasive group was less than that of open surgery group. CONCLUSIONS: BEIS technique has the advantage of less trauma, less bleeding for lumbar stenosis when compared to open surgery. It can better alleviate the postoperative local lumbar pain, and early-middle clinical effect is equivalent to open surgery, so it can be used as a safe and effective surgical treatment for lumbar spinal stenosis.

Ruthenium-Catalyzed ortho- and meta-H/D Exchange of Arenes.

Ruthenium-catalyzed aromatic H/D exchange in [D4]acetic acid has been developed. By using N-heteroarenes as directing groups, both ortho and meta positions are selectively deuterated with high levels of D incorporation. Moreover, this strategy provides an alternative way to achieve meta-C-H activation.

Access to dihydropyridinones and spirooxindoles: application of N-heterocyclic carbene-catalyzed [3+3] annulation of enals and oxindole-derived enals with 2-aminoacrylates.

A strategy for the NHC-catalyzed synthesis of dihydropyridinones and spirooxindoles has been developed via [3+3] annulation reactions of enals or isatin-derived enals with 2-aminoacrylates under oxidative conditions. In this efficient strategy, the 2-aminoacrylates served as nucleophiles. Modifying the standard base switched the carbon-carbon double bond formation from 5,6-positions to 3,4-positions to generate 5,6-dihydropyridinones and 3,4-dihydropyridinones, respectively. Meanwhile, a diverse set of spirooxindole derivatives were also synthesized in good to excellent yields.

[Excision of necrotic and infected tissues combined with induced membrane and external fixator technique for the treatment of chronic osteomyelitis in tibia after fracture operation].

OBJECTIVE: To investigate the clinical efficacy of excision of necrotic and infected tissues combined with induced membrane and external fixator technique to treat chronic osteomyelitis in tibia after fracture operation. METHODS: From June 2011 to June 2014, a total of 13 patients with tibia osteomyelitis were treated with excision of necrotic and infected tissues and external fixator technique in the first stage. There were 8 males and 5 females, ranging in age from 16 to 67 years old with an average of (37.3±14.3) years old. Within 6 to 8 weeks the induced membrane was formed and the induced membrane technique was applied to promote new bone forming in the second stage. RESULTS: Thirteen patients had no reinfection and achieved complete bone healing after 24 to 52 months follow-up. All the patients had satisfactory function. CONCLUSIONS: Excision of necrotic and infected tissues combined with induced membrane and external fixator technique to treat chronic osteomyelitis in tibia after fracture operation can provide satisfactory results.

Enantioselective [3 + 2] Annulation of Enals with 2-Aminoacrylates Catalyzed by N-Heterocyclic Carbene.

A novel and convenient strategy for the enantioselective synthesis of γ-lactam derivatives via N-heterocyclic carbene catalyzed formal [3 + 2] annulation of enals with 2-aminoacrylates is disclosed. This activation mode provides a complementary approach to the synthesis of various γ-lactam derivatives in good yields with excellent diastereo- and enantioselectivities. In this process, two consecutive stereocenters are constructed, and a quaternary carbon center is also established.

CD1 Mouse Retina Is Shielded From Iron Overload Caused by a High Iron Diet.

PURPOSE: High RPE iron levels have been associated with age-related macular degeneration. Mutation of the ferroxidase ceruloplasmin leads to RPE iron accumulation and degeneration in patients with aceruloplasminemia; mice lacking ceruloplasmin and its homolog hephaestin have a similar RPE degeneration. To determine whether a high iron diet (HID) could cause RPE iron accumulation, possibly contributing to RPE oxidative stress in AMD, we tested the effect of dietary iron on mouse RPE iron. METHODS: Male CD1 strain mice were fed either a standard iron diet (SID) or the same diet with extra iron added (HID) for either 3 months or 10 months. Mice were analyzed with immunofluorescence and Perls' histochemical iron stain to assess iron levels. Levels of ferritin, transferrin receptor, and oxidative stress gene mRNAs were measured by quantitative PCR (qPCR) in neural retina (NR) and isolated RPE. Morphology was assessed in plastic sections. RESULTS: Ferritin immunoreactivity demonstrated a modest increase in the RPE in 10-month HID mice. Analysis by qPCR showed changes in mRNA levels of iron-responsive genes, indicating moderately increased iron in the RPE of 10-month HID mice. However, even by age 18 months, there was no Perls' signal in the retina or RPE and no retinal degeneration. CONCLUSIONS: These findings indicate that iron absorbed from the diet can modestly increase the level of iron deposition in the wild-type mouse RPE without causing RPE or retinal degeneration. This suggests regulation of retinal iron uptake at the blood-retinal barriers.

Ag island film-enhanced rare earth co-luminescence effect of Tb-Gd-protein-sodium dodecyl benzene sulfonate system and sensitive detection of protein.

This paper reported the coupling technique of Ag island film-enhanced fluorescence with rare earth co-luminescence effect of Tb-Gd-sodium dodecyl benzene sulfonate (SDBS)-protein system. While the collagen is used as the separator between Ag island film and the fluorophore because it not only can decrease the fluorescence of the blank, but also can promote the adsorption of other proteins and change the conformation of the protein. The effects of Ag island film on both the fluorescence and resonance energy transfer process of Tb-Gd-SDBS-protein system are studied, finding that Ag island film can enhance the energy transfer efficiency of this system, resulting in fluorescence enhancement about tenfold compared with this system without Ag island film. Therefore, this technique is used for the detection of proteins as low as 0.72 ng/mL for BSA and 1.3 ng/mL for HSA. In addition, Ag island film can also change the energy transfer process of Tb-SDBS-protein system.

[Position and orientation of zygomatic-area implant of zygo-buccal flange osseointegrated implant obturator].

OBJECTIVE: To provide objective data for position and orientation of zygomatic-area implant used in zygo-buccal flange osseointegrated implant obturator for patients with large maxillary defect. METHODS: Fifty cases of normal unilateral zygomatic body with dentition were measured on three-dimensional spiral CT images. Measurements included the slope angle of zygomatic body on sagittal sectional image, the maximal horizontal distance from the buccal boundary of maxillary alveolar to outboard of maxillary sinus. Furthermore, the configuration of zygomatic body was observed on coronal sectional image. RESULTS: The average rearward slope angle of zygomatic-body was 80.03 degrees. Forty-eight cases showed straight zygomatic-body configurations and two cases quite curvy. The maximal horizontal distance from the buccal boundary of maxillary alveolar to outboard of maxillary sinus was 6.77 mm. CONCLUSIONS: In a normal condition, implants can be upright inserted tilting about 10 degrees ahead to utilize much zygomatic bone-volume in high site. In order to improve security and validity of implantation, it is better to take spiral CT examination to evaluate the bone volume and shape of zygomatic body before zygomatic-area implant.