Preparation of luteolin loaded nanostructured lipid carrier based gel and effect on psoriasis of mice.

This study investigated a nanostructured lipid carrier (NLC)-gel system containing luteolin (LUT), a potential drug delivery system for the treatment of psoriasis. LUT-NLC was prepared by solvent emulsification ultrasonication method. The particle size was 199.9 ± 2.6 nm, with the encapsulation efficiency of 99.81% and drug loading of 4.06%. X-ray diffractometry (XRD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to characterize the LUT-NLC. The NLC was dispersed in Carbomer 940 to form the NLC based gel. The rheological characteristics of LUT-NLC-gel showed an excellent shear-thinning behavior (non-Newtonian properties) and coincided with the Herschel-Bulkley model. LUT-NLC-gel (78.89 µg/cm2) exhibited better permeation properties and released over 36 hours than LUT gel (32.17 µg/cm2). The dye-labeled LUT-NLC presented intense fluorescence in the epidermis and dermis by the visualization of fluorescence and confocal microscopy, and it could accumulate in the hair follicles. The effect of LUT-NLC-gel on imiquimod-induced psoriasis mice was evaluated by psoriasis area severity index scoring, spleen index assay, histopathology, and inflammatory cytokines. These results confirmed that LUT-NLC-gel with high dose (80 mg/kg/day) remarkably reduced the level of inflammatory and proliferation factors such as TNF-α, IL-6, IL-17, and IL-23 in both skin lesions and blood. LUT-NLC-gel improved the macroscopic features. Therefore, the LUT-NLC-gel had great potential as an effective delivery system for skin diseases.

Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests.

BACKGROUND: The differentiation of human induced pluripotent stem cells (iPSCs) into oocytes, which involves the transformation from mitosis to meiosis, has been a hotspot of biological research for many years and represents a desirable experimental model and potential strategy for treating infertility. At present, studies have shown that most cells stagnate in the oogonium stage after differentiation into primordial germ cells (PGCs) from human iPSCs. METHODS: iPSCs carrying a SYCP3-mkate2 knock-in reporter were generated by the CRISPR/Cas9 strategy to monitor meiosis status during induced differentiation from iPSCs into oocytes. These induced PGCs/oogonia were activated by small molecules from the Wnt signaling pathway and then cocultured with reconstructed human ovarian nests in vivo for further development. RESULTS: First, human PGCs and oogonia were efficiently induced from iPSCs. Second, induced dormant PGCs resumed meiosis and then differentiated into primary oocytes through the in vitro activation of the Wnt signaling pathway. Finally, a new coculture system involving the reconstruction of ovarian nests in vitro could facilitate the differentiation of oocytes. CONCLUSIONS: Human PGCs/oogonia induced from iPSCs can be activated and used to resume meiosis by molecules of the Wnt signaling pathway. The coculture of activated PGCs and reconstruction of ovarian nests facilitated differentiation into primary oocytes and the generation of haploid human oocytes in vivo. These findings established a new strategy for germline competence in primary oocytes and provided a keystone for human gametogenesis in vitro and in vivo.

Solid lipid nanoparticles as an effective sodium aescinate delivery system: formulation and anti-inflammatory activity.

Sodium aescinate-loaded solid lipid nanoparticles were fabricated using a melt-emulsification and ultrasonication method. Based on mean particle size, polydispersity index, and encapsulation efficiency, orthogonal and Box-Behnken designs were applied to optimize solid lipid nanoparticles with single emulsification and double emulsification methods. The characterization of solid lipid nanoparticles was investigated by X-ray diffractometry, differential scanning calorimetry, and scanning electron microscopy. After optimization of sodium aescinate-loaded solid lipid nanoparticles with single emulsification, the particle size was 90.7 nm and encapsulation efficiency was 76.5%. The sodium aescinate-loaded solid lipid nanoparticles with double emulsification were negatively charged spherical particles with the size of 109.4 nm and encapsulation efficiency up to 86.6%. Both solid lipid nanoparticles with single emulsification and double emulsification exhibited sustained release for 12 h without an initial burst release. The results indicated that sodium aescinate-loaded solid lipid nanoparticles by double emulsification showed more drug loading and stability after reconstitution. The sodium aescinate-solid lipid nanoparticles with double emulsification demonstrated stronger anti-inflammatory activity, including paw edema and ear swelling in mice than that of free sodium aescinate. Therefore, solid lipid nanoparticles have great potential as an effective sodium aescinate delivery system for application in medicine.

Effect of Applying Binocular Visual Training after Slanted Lateral Rectus Recession on Orthophoric Rate and Binocular Visual Function Recovery on Patients with Convergence Insufficiency-Type Intermittent Exotropia.

OBJECTIVE: To explore the effect of applying binocular visual training after slanted lateral rectus recession on orthophoric rate and binocular visual function recovery on patients with convergence insufficiency-type intermittent exotropia (CI-IXT). METHODS: A total of 76 CI-IXT child patients treated at the Strabismus and Pediatric Ophthalmology Department of our hospital from June 2019 to June 2020 were selected as the research objects, and those who met the inclusion criteria were equally divided into group A (63 eyes) and group B (61 eyes) according to the sealed envelope randomization. All child patients accepted the slanted lateral rectus recession, and after that, those in group A accepted the binocular visual training and those in group B accepted the conventional visual function rehabilitation training, so as to compare their position of eye, the best corrected visual acuity, etc., after training for statistical analysis. RESULTS: Compared with group B after one month of surgery, group A had significantly less patients with grade I binocular vision function (P < 0.001) and more patients with grade II and III vision function (P < 0.05); between group A and group B, after 3 months and 6 months of treatment, the number of eyes with normal stereoscopic vision was significantly higher in group A (P < 0.05); at 15 days, 1 month, 3 months, and 6 months of treatment, the visual strain scores of group A were significantly lower (P < 0.001); after treatment, the number of orthophoria eyes was significantly higher in group A (P < 0.001), while the numbers of overcorrected eyes and undercorrected eyes were significantly higher in group B (P < 0.001); and the total incidence rate of adverse reactions was significantly lower in group A (P < 0.05). CONCLUSION: Applying binocular visual training to child patients with CI-IXT after slanted lateral rectus recession can promote the recovery of binocular vision and ensure higher safety, and further study will help to establish a better solution for the affected children.

A versatile and multifunctional metal-organic framework nanocomposite toward chemo-photodynamic therapy.

Previously most of the applications of targeting components have been based on the enhanced permeability and retention effect achieved using folic acid, which consider the side effects of the targeting components to some extent. Herein, we report a new strategy to decorate the surface of MOFs using a pemetrexed (MTA) targeting molecule, affording a new drug delivery system of ALA@UIO-66-NH-FAM/MTA (ALA = 5-amino-levulinic acid and FAM = 5-carboxyfluorescein). The confocal microscopy and flow cytometry results showed that ALA@UIO-66-NH-FAM/MTA presented a better targeting effect compared to ALA@UIO-66-NH-FAM/FA (FA = folic acid) and indicated a gradually increasing tendency of the targeting effect with the increasing expression of folate receptors on the tumor cell cytomembrane. Furthermore, the cytotoxicity experiment indicates that the combination of chemotherapy and photodynamic therapy is a more effective therapy model than single chemotherapy and photodynamic therapy. This work demonstrates the first attempt at folic acid antagonist (MTA) modification for NMOFs, providing a new concept for the design of MOFs with folate receptor targeting capacity for clinical applications.

Botulinum Toxin Injection with Conjunctival Microincision for the Treatment of Acute Acquired Comitant Esotropia and Its Effectiveness.

PURPOSE: To report on an improved botulinum toxin injection with conjunctival microincision for beginners, and to determine the effectiveness of botulinum toxin A (BTXA) in the treatment of patients with acute acquired comitant esotropia (AACE). METHODS: Medical records of 29 AACE patients were retrospectively analyzed. BTXA was injected into the unilateral or bilateral medial rectus muscle with conjunctival microincision without electromyographic guidance. Success was defined as total horizontal deviation ≤10 prism diopters (PD) and evidence of binocular vision. RESULTS: Twenty-nine patients were included, of whom 22 were male and 7 were female. The mean age at onset was 14.2 ± 7.4 (range, 4-34) years. The mean time from onset of AACE to injection was 18.4 ± 20.3 (range, 1-96) weeks. All patients completed at least 6 months of follow-up, and the mean follow-up after BTXA injection was 12.3 ± 4.8 months (range, 7-24 months). Neurological evaluation and brain magnetic resonance imaging (MRI) were unremarkable in all patients. The mean spherical equivalent refraction was -1.22 ± 2.85D and -0.97 ± 2.80D in the right and left eyes, respectively. Mean preinjective esotropia was 38.4 ± 18.9 PD (range, +10-+80 PD) at near and 40.2 ± 17.7 PD (range, +20-+80 PD) at far distance. The mean angle of deviation at 6 months after injection was 0.6 ± 4.1 PD (range, -3-+15 PD) at near and 3.0 ± 5.9 PD (range, 0-+20 PD) at far distance. There was significant difference in the angle of deviation at near and far fixation between pre-BTXA and post-BTXA 6 months (p < 0.001, p < 0.001, resp.). There was no significant difference in the angle of deviation at near and far fixation between post-BTXA 6 months and post-BTXA at final follow-up (p = 0.259 and 0.326, resp.). Mean stereoacuity improved from 338 to 88 arc seconds. During the follow-up period, 5 of 29 patients had recurrent esotropia. Two patients refused all further treatment, and the other 3 patients required incisional strabismus surgery. The success rates were 86.2% (25/29) at 6 months and 82.8% (24/29) at final follow-up. CONCLUSION: Conjunctival microincision injection of botulinum toxin is a practical and safe method for beginners to locate an extraocular muscle, which is as effective as the traditional methods. Botulinum toxin injection can be preferred as the first-line treatment for AACE patients with potential binocular vision.

Design of Metal-Organic Frameworks for pH-Responsive Drug Delivery Application.

Metal-Organic Frameworks (MOFs) have aroused great interest in the field of nanoscience and nanotechnology particularly in biomedical domains, such as Drug Delivery System (DDS), Biomedical Imaging (BI) and Photodynamic Therapy (PDT). As an emerging material, MOFs possess extraordinarily high surface area, controllable particle size and good biocompatibility. With extraordinary flexibility in the selection of organic and inorganic components, MOFs can rationally be tuned to obtain the materials having versatile structures and porosities. MOFs can serve as ideal vehicles for DDS, BI and PDT through modification and function. In this review, we summarized the design and synthetic strategies for preparing MOFs and introduced their recent advanced usage in DDS, BI and PDT. Finally, the prospect and future challenges of these nanomaterials are also documented.

A New 3D 10-Connected Cd(II) Based MOF With Mixed Ligands: A Dual Photoluminescent Sensor for Nitroaroamatics and Ferric Ion.

The precise unification of functional groups and photoluminescence properties can give rise to MOFs that can offer diverse applications like selective detection of nitroaromatic compounds (NACs) which are considered to be an important ingredient of explosive as well as cation and anion sensing. Hence, a new 3D metal-organic framework (MOF) [Cd2(btc)(bib)(HCOO)(H2O)·H2O]n (1) has been synthesized using mixed ligand strategy by solvothermal reaction of cadmium acetate with two ligands viz. 1,3,5-benzenetricarboxylic acid (H3btc) and 1,4-bis(2-methyl-imidazol-1-yl)butane (bib). The MOF 1 possesses highly 10-connected network which is based on {Cd4(btc)2(bib)4} molecular building block. The studies showed that 1 could be taken as the fluorescent sensor for sensitive recognition of NACs, in particular 2,4,6-trinitrophenol (TNP) with notable quenching (K sv = 5.42 × 104 M-1) and LOD of 1.77 ppm. Additionally, 1 also displayed selective sensing for Fe3+ ions with K sv = 6.05 × 103 M- 1 and LOD = 1.56 ppm. Also, this dual sensor displayed excellent reusability toward the detection of TNP and Fe3+ ion. Theoretical calculations have been performed to propose the probable mechanism for the sensing luminescence intensity. Calculations indicated that because of the charge transfer and weak interaction that is operating between NACs and MOF, the weakening in the photoluminescence intensity resulted.

Recent developments on zinc(ii) metal-organic framework nanocarriers for physiological pH-responsive drug delivery.

The high storage capacities and excellent biocompatibilities of zinc(ii) metal-organic frameworks (Zn-MOFs) have made them outstanding candidates as drug delivery carriers. Recent studies on the pH-responsive processes based on carrier-drug interactions have proven them to be the most efficient and effective way to control the release profiles of drugs. To satisfy the ever-growing demand in cancer therapy, great efforts are being devoted to the development of methods to precisely control drug release and achieve targeted use of an active substance at the right time and place. In this review article, we discuss the diverse stimuli based on Zn-MOFs carriers that have been achieved upon external activation from single pH-stimulus-responsive or/and multiple pH-stimuli-responsive viewpoints. Also, the perspectives and future challenges in this type of carrier system are discussed.

Root Zone Cooling and Exogenous Spermidine Root-Pretreatment Promoting Lactuca sativa L. Growth and Photosynthesis in the High-temperature Season.

Root zone high-temperature stress is a major factor limiting hydroponic plant growth during the high-temperature season. The effects of root zone cooling (RZC; at 25°C) and exogenous spermidine (Spd) root-pretreatment (SRP, 0.1 mM) on growth, leaf photosynthetic traits, and chlorophyll fluorescence characteristics of hydroponic Lactuca sativa L. grown in a high-temperature season (average temperature > 30°C) were examined. Both treatments significantly promoted plant growth and photosynthesis in the high-temperature season, but the mechanisms of photosynthesis improvement in the hydroponic grown lettuce plants were different between the RZC and SRP treatments. The former improved plant photosynthesis by increasing stoma conductance (G s) to enhance CO2 supply, thus promoting photosynthetic electron transport activity and phosphorylation, which improved the level of the photochemical efficiency of photosystem II (PSII), rather than enhancing CO2 assimilation efficiency. The latter improved plant photosynthesis by enhancing CO2 assimilation efficiency, rather than stomatal regulation. Combination of RZC and SRP significantly improved P N of lettuce plants in a high-temperature season by both improvement of G s to enhance CO2 supply and enhancement of CO2 assimilation. The enhancement of photosynthetic efficiency in both treatments was independent of altering light-harvesting or excessive energy dissipation.

[BIOMECHANICAL RESEARCH OF DIFFERENT INTERNAL FIXATIONS USING LOCKING RECONSTRUCTION PLATE FOR ACETABULAR TRANSVERSE FRACTURE].

OBJECTIVE: To compare the biomechanical stability of acetabular transverse fracture fixed with single column locking reconstruction plate, locking reconstruction plate combined with lag screw, and double columns lag screws. METHODS: Acetabular transverse fractures were established in 20 adult fresh semi-pelvis specimens, and divided into 5 groups randomly (n=4). The anterior columns were fixed with locking reconstruction plates in group A; the posterior columns were fixed with locking reconstruction plates in group B; the anterior columns were fixed with locking reconstruction plates and the posterior columns with lag screws in group C; the anterior columns were fixed with lag screws and the posterior columns with locking reconstruction plates in group D; the double columns were fixed with lag screws in group E. When loading three times weight, the longitudinal displacement of fracture fragment was measured, and the shear rigidity was calculated to compare the stability among groups. RESULTS: The longitudinal displacement of groups A and B were significantly greater than that of groups C, D, and E (P<0.05), and the shear rigidity of groups A and B were significantly lower than that of groups C, D, and E (P< 0.05). The longitudinal displacement of group B was significantly greater than that of group A (P< 0.05), but no significant difference was found in the shear rigidity between groups A and B (P>0.05). There was no significant difference in the longitudinal displacement and shear rigiditramong groups C, D, and E (P>0.05). CONCLUSION: Locking reconstruction plate combined with lag screw and double columns lag screws have similar stability, they have stronger stability than the single column locking reconstruction plate. The stability of anterior column locking reconstruction plate is better than that of the posterior column locking reconstruction plate.

cAMP level modulates scleral collagen remodeling, a critical step in the development of myopia.

The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP). We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs). Form-deprived myopia (FDM) was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and returned to normal levels after unmasking and recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC) activator forskolin resulted in a myopic shift accompanied by reduced collagen mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen mRNA levels and collagen secretion by HSFs. The inhibition was reversed by SQ22536. These results demonstrate a critical role of cAMP in control of myopia development. Selective regulation of cAMP to control scleral collagen synthesis may be a novel therapeutic strategy for preventing and treating myopia.

[Chromosome karyotype and Y chromosome microdeletion analysis in 133 idiopathic male infertile patients].

OBJECTIVE: To explore the relationship between chromosomal abnormalities and Y chromosome microdeletions in idiopathic male infertile patients. METHODS: Karyotypic analysis and PCR were carried out in 133 male idiopathic infertile patients for chromosome karyotype and Y chromosome microdeletion analysis. RESULTS: Of the 133 patients, 25 (18.80%) were found to have chromosome abnormalities, and 12 (9.02%) were found to have Y chromosome microdeletions including 2 with varicocele and 2 with cryptorchism. Four patients had both chromosomal abnormalities and Y chromosome microdeletions. CONCLUSION: The chromosomal abnormalities and Y chromosome microdeletions may play an important role in idiopathic male infertility, suggesting the importance of examinations of chromosomal abnormalities and Y chromosome microdeletions in such patients.