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Purpose: To examine the associations of near work related parameters with spherical equivalent refraction and axial length in Chinese children. Methods: A total of 1770 grade 7 students with mean age of 12.7 years were examined with cycloplegic autorefraction and axial length. Questions were asked regarding time spent in near work and outdoors per day, and near work related parameters. Results: Multivariate models revealed the following associations with greater odds of myopia: continuous reading (> 45min), odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8; close television viewing distance (≤ 3m), OR, 1.7; 95% CI, 1.2-2.3; head tilt when writing, OR, 1.3; 95% CI, 1.1-1.7, and desk lighting using fluorescent vs. incandescent lamp, OR, 1.5; 95% CI, 1.2-2.0. These factors, together with close reading distance and close nib-to-fingertip distance were significantly associated with greater myopia (P<0.01). Among near work activities, only reading more books for pleasure was significantly associated with greater myopia (P=0.03). Television viewing distance (≤ 3 m), fluorescent desk light, close reading distance (≤20 cm) and close nib-to-fingertip distance (≤ 2 cm) were significantly associated with longer axial length (P<0.01). Reading distance, desk light, and reading books for pleasure had significant interaction effects with parental myopia. Conclusions: Continuous reading, close distances of reading, television viewing and nib-to-fingertip, head tilt when writing, reading more books for pleasure and use of fluorescent desk light were significantly associated with myopia in 12-year-old Chinese children, which indicates that visual behaviors and environments may be important factors mediating the effects of near work on myopia. [ABSTRACT FROM AUTHOR]

Compares skinned fibers from bovine ventricle and slow rabbit soleus muscle with respect to the effects of force and sarcomere length on calcium (Ca2+) binding to troponin C. Effect of vanadate on force generation and calcium binding; Effect of length changes on Ca2+ binding.

A MOF named [(CH3)NH2] [H2N(CH3)2][ZnTNC4A] ⋅ 4H2O (ZnTNC4A) was synthesized by a resorcinol[4]arene functionalized tetracarboxylic acid ligand (TNC4A=2,8,14,20‐tetra‐1‐naphthalene‐6,12,18,24‐tetramethoxy‐4,10,16,22‐ tetracarboxyl‐methoxy‐resorin[4]arene). The three‐dimensional framework with one‐dimensional channels of ZnTNC4A was characterized by elemental analysis, powder X‐ray diffraction, thermogravimetry, UV‐vis diffuse reflection spectrum, infrared spectrum and N2 adsorption analyse. In addition, ZnTNC4A shows the ability of selective adsorption of methylene blue with a pseudo‐second order kinetic model. The selective adsorption kinetics of a series of dyes showed that the ion exchanged separation process was related to the size and charge of organic dyes. [ABSTRACT FROM AUTHOR]

Objective To observe the expression profiles of osteoblast-related genes in human mesenchymal stem cells (MSCs) derived from bone marrow during osteogenic differentiation. Methods MSCs were induced to differentiate with MSC osteogenic differentiation medium for 7, 14, 21 and 28 days respectively. Alizarin Red staining was used to detect matrix mineralization. Expression of osteoblast-related genes, including osteocalcin, osteopontin, Runt-related transcription factor 2 (Runx2), alkaline phosphatase and collagen type I, was assessed with quantitative reverse transcription-polymerase chain reaction. Results On day 14 after induction of differentiation, cells were stained positively with Alizarin Red. The expression levels of these genes exhibited an upward trend as induction time was prolonged. Exposure to osteogenic differentiation medium less than 21 days did not significantly induce osteocalcin expression; osteocalcin expression levels in the differentiated cells induced for 21 and 28 days were 1.63 and 2.46 times as high as the undifferentiated cells respectively (all P <0.05). Stimulation with MSC osteogenic differentiation medium over 14 days significantly enhanced bone marrow-derived MSCs to express osteopontin and Runx2 genes (all P <0.05). Osteogenic differentiation medium could significantly induce the expressions of alkaline phosphatase and collagen type I genes (all P <0.05). Their expressions reached the peak levels on day 21, which were increased more than 4- and 3-fold respectively. Conclusion Human bone marrow-derived MSCs could exhibit the sequential expression pattern of osteoblast marker genes during osteogenic differentiation in vitro. [ABSTRACT FROM AUTHOR]

Neurological disorders affect a large population, often leading to different levels of disability and resulting in decreased quality of life. Due to the limited recovery obtained from surgical procedures and other medical approaches, a large number of patients with prolonged dysfunction receive neurorehabilitation protocols to improve their neural plasticity and regeneration. However, the poor neural regeneration ability cannot effectively rebuild the tissue integrity and neural functional networks; consequently, the prognoses of neurorehabilitation remain undetermined. To increase the chances of neural regeneration and functional recovery for patients with neurological disorders, regenerative rehabilitation was introduced with combined regenerative medicine and neurorehabilitation protocols to repair neural tissue damage and create an optimized biophysical microenvironment for neural regeneration potential. With the deepening of exosome research, an increasing number of studies have found that the systemic therapeutic effects of neurorehabilitation approaches are mediated by exosomes released by physically stimulated cells, which provides new insight into rehabilitative mechanisms. Meanwhile, exosome therapy also serves as an alternative cell-free therapy of regenerative medicine that is applied in partnership with neurorehabilitation approaches and formulates exosome-based neurological regenerative rehabilitation. In this study, we review the current state of exosome-associated neurorehabilitation. On the one hand, we focus on presenting the varied mediating effects of exosomes in neurorehabilitation protocols of specific neurological pathologies; on the other hand, we discuss the diverse combinations of exosome therapies and neurorehabilitation approaches in the field of neurological regenerative rehabilitation, aiming to increase the awareness of exosome research and applications in the rehabilitation of neurological disorders. [Display omitted] • Exosome-based regenerative rehabilitation bring great dawn to neurorehabilitation. • Exosome-mediated pathways play crucial parts in neurorehabilitation. • Exosome therapy enhances the neurorehabilitation by promoting neural regeneration. [ABSTRACT FROM AUTHOR]

Abstract: Background: PBC is a prototypical autoimmune liver disease characterized by portal lymphoplasmacyte infiltration. ALD is a prototypical environment‐driven disease, featured by mild lymphocyte infiltration. We hypothesize that B cells are more involved in the pathogenesis of PBC. By analysing the infiltrating B cell repertoire, we aimed to unveil greater oligoclonal expansion and active clonal exchange between liver and periphery in PBC than in ALD patients. Methods: Using NGS of Ig H chain genes, we analysed the liver‐infiltrating and paired peripheral B lymphocyte repertoire from nine PBC and four ALD patients. Results: In the liver of PBC and ALD patients, (i) roughly 10% of the B lymphocytes were clonally related and highly expressed, and there were also lineages that underwent extensive clonal expansion; (ii) there was different use of IGHV/IGHJ segments between PBC and ALD, suggesting distinct Ag exposure backgrounds, but this did not lead to a significant difference in their clonal expansion level. Analysis of data sets from paired samples further revealed, (iii) direct clonal exchange and evolutionally related B cell clones between the infiltrating and peripheral repertoire; (iv) the seeding of the infiltrating clones to periphery, and peripheral ones to the liver, for further extensive evolution. Conclusions: The oligoclonally expanded nature of the infiltrating B cell repertoire implies B cell immunity is involved in the pathogenesis of both diseases. The observed clonal exchange might provide an approach to identify and monitor the infiltrating B cells through the periphery. [ABSTRACT FROM AUTHOR]

The accurate estimation of the underlying number of components in complex samples is critical in data analysis. A new chemometric strategy was developed in this study to determine accurately the number of underlying components in complex samples. First, discrete Fourier transformation was used to project the eigenvectors from the singular value decomposition to the frequency space. A robust statistical analysis based on iterative t -test was then employed to eliminate the outliers in the Fourier coefficients of each eigenvector. Finally, ANOVA was used to differentiate the meaningful components from noise. Simulated and published fluorescence datasets were used to demonstrate the strategy. Results indicate that the proposed strategy accurately and efficiently estimated the number of underlying components in the analyzed dataset. Moreover, the performance of the proposed method was comparable with the well-known core consistency diagnostic and Monte Carlo simulation coupled with frequency location methods. The new technique coupled with second-order calibration was successfully used to resolve the problem of seriously overlapped fluorescence spectra in the accurate quantification of fluoroquinolone antibiotics in tap water samples. Second-order advantage was achieved. [ABSTRACT FROM AUTHOR]

This study examines the geochemical and whole-rock Sr–Nd–Pb isotopic compositions of Early Cretaceous volcanic rocks of the southern Jilin Province (Tonghua and Huanren areas) and Liaodong Peninsula (Xiuyan, Dandong, and Guiyunhua areas), northeastern North China Craton (NCC). Two groups of volcanic rocks are recognized in the northeastern NCC. The geochemistry and isotopic compositions of the intermediate-acid volcanic rocks indicate that a systematic decrease in whole-rock ε Nd (t) is accompanied by an increase of Zr/Nb. Modeling results suggest that those intermediate-acid volcanic rocks experienced the assimilation-fractional crystallization (AFC) process with different lower continental crust (LCC) components, indicating the heterogeneity of LCC in the northeastern NCC. As for basic volcanic rocks, they are characterized by "weakly enriched" isotopic signatures, i.e., moderately radiogenic Sr (0.7062–0.7082), unradiogenic Nd (−5.29 to −1.14), and highly radiogenic Pb compositions. The narrow scope of Sr–Nd–Pb isotopic compositions of whole-rock indicates insignificant crustal assimilation. Instead, the high Th/Yb ratios were largely inherited from source enrichment through the input of subducted sediment. Furthermore, element-isotopic modeling suggests that the "weakly enriched" mantle-derived rocks have resulted from a depleted mantle source metasomatized via the sediment-derived melt. Our results provide powerful petrological and geochemical evidence on the Early Cretaceous subduction of the Paleo-Pacific plate beneath the northeastern NCC and suggest the metasomatic process by subducted sediment-derived melt may play an important role in depleted mantle enrichment. • The volcanic rocks in the northeastern NCC erupted at 112–132 Ma. • Origin of felsic volcanic rocks implied involvement of heterogeneous NCC crust. • The mantle source was metasomatized by melt of subducted Paleo-Pacific sediment. [ABSTRACT FROM AUTHOR]

Although highly appealing for rapid access of molecular complexity, multi-functionalization of alkenes that allows incorporation of more than two functional groups remains a prominent challenge. Herein, we report a novel strategy that merges dipolar cycloaddition with photoredox promoted radical ring-opening remote C(sp3)-H functionalization, thus enabling a smooth 1,2,5-trifunctionalization of unactivated alkenes. A highly regioselective [3+2] cycloaddition anchors a reaction trigger onto alkene substrates. The subsequent halogen atom transfer (XAT) selectively initiates ring-opening process, which is followed by a series of 1,5-hydrogen atom transfer (1,5-HAT) and intermolecular fluorine atom transfer (FAT) events. With this method, site-selective introduction of three different functional groups is accomplished and a broad spectrum of valuable β-hydroxyl-ε-fluoro-nitrile products are synthesized from readily available terminal alkenes., (© 2024 Wiley‐VCH GmbH.)

In the realm of genetically transformed crops, the process of plant regeneration holds utmost significance. However, the low regeneration efficiency of several wheat varieties currently restricts the use of genetic transformation for gene functional analysis and improved crop production. This research explores overexpression of TaLAX PANICLE1 (TaLAX1), which markedly enhances regeneration efficiency, thereby boosting genetic transformation and genome editing in wheat. Particularly noteworthy is the substantial increase in regeneration efficiency of common wheat varieties previously regarded as recalcitrant to genetic transformation. Our study shows that increased expression of TaGROWTH-REGULATING FACTOR (TaGRF) genes, alongside that of their co-factor, TaGRF-INTERACTING FACTOR 1 (TaGIF1), enhances cytokinin accumulation and auxin response, which may play pivotal roles in the improved regeneration and transformation of TaLAX1-overexpressing wheat plants. Overexpression of TaLAX1 homologs also significantly increases the regeneration efficiency of maize and soybean, suggesting that both monocot and dicot crops can benefit from this enhancement. Our findings shed light on a gene that enhances wheat genetic transformation and elucidate molecular mechanisms that potentially underlie wheat regeneration., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Plant inflorescence architecture is determined by inflorescence meristem (IM) activity and controlled by genetic mechanisms associated with environmental factors. In Arabidopsis (Arabidopsis thaliana), TERMINAL FLOWER1 (TFL1) is expressed in the IM and is required to maintain indeterminate growth, whereas LEAFY (LFY) is expressed in the floral meristems (FMs) formed at the periphery of the IM and is required to activate determinate floral development. Here, we address how Arabidopsis indeterminate inflorescence growth is determined. We show that the 26S proteasome subunit REGULATORY PARTICLE AAA-ATPASE 2a (RPT2a) is required to maintain the indeterminate inflorescence architecture in Arabidopsis. rpt2a mutants display reduced TFL1 expression levels and ectopic LFY expression in the IM and develop a determinate zigzag-shaped inflorescence. We further found that RPT2a promotes DNA METHYLTRANSFERASE1 degradation, leading to DNA hypomethylation upstream of TFL1 and high TFL1 expression levels in the wild-type IM. Overall, our work reveals that proteolytic input into the epigenetic regulation of TFL1 expression directs inflorescence architecture in Arabidopsis, adding an additional layer to stem cell regulation., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo . In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway., Competing Interests: The authors declare that they have no conflict of interests., (© 2024 The Author(s).)

Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates neuronal damage, although the underlying mechanism remains unclear. The present study aimed to investigate the role of NTRK1 in mouse hippocampal neuronal damage and the specific mechanism. A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage. Next, an in vitro analysis was conducted using the CCK-8 assay, TUNEL assay, NeuN IF staining, DCFH-DA staining, JC-1 staining, ATP content test, mRFP-eGFP-LC3 assay, and LC3-II IF staining to elucidate the effect of NTRK1 on mouse hippocampal neuronal activity, apoptosis, damage, mitochondrial function, and autophagy. Subsequently, rescue experiments were performed by subjecting the NTRK1-knockdown neurons to pre-treatment with O304 and Rapamycin. The AMPK/ULK1/FUNDC1 pathway activity and mitophagy were detected using western blotting (WB) analysis. Resultantly, in vivo analysis revealed that NTRK1 knockdown induced mouse cognitive impairment and hippocampal tissue damage, in addition to inactivating the AMPK/ULK1/FUNDC1 pathway activity and mitophagy in the hippocampal tissues of mice. The treatment with BAY-3827 exacerbated the mouse depressive-like behavior induced by NTRK1 knockdown. The results of in vitro analysis indicated that NTRK1 knockdown attenuated viability, NeuN expression, ATP production, mitochondrial membrane potential, and mitophagy, while enhancing apoptosis and ROS production in mouse hippocampal neurons. Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage., (© 2023. The Author(s).)

Purpose: The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial., Methods and Materials: Pediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). The PedsQL3.0 Cancer Module (PedsQL) survey assessed quality of life and was administered to the patient and guardian at RT simulation, midway through RT, and at final treatment. The modified Yale Preoperative Anxiety Scale (mYPAS) assessed anxiety and was performed at the same 3 time points. Success was evaluated using the χ 2 test. PedsQL and mYPAS scores were assessed using mixed effects models with time points evaluated as fixed effects and a random intercept on the subject., Results: Eighty-one children were included; median age was 7 years. AVATAR was successful at all 10 institutions and with photon and proton RT. There were 63 (78%) S patients; anesthesia was avoided for a median of 20 fractions per patient. Success differed by age (P = .04) and private versus public insurance (P < .001). Both patient (P = .008) and parent (P = .006) PedsQL scores significantly improved over the course of RT for patients aged 5 to 7. Anxiety in the treatment room decreased for both S and NS patients over RT course (P < .001), by age (P < .001), and by S versus NS patients (P < .001)., Conclusions: In this 10-center prospective trial, anesthesia avoidance with AVATAR was 78% in children aged 3 to 10 years, higher than among age-matched historical controls (49%; P < .001). AVATAR implementation is feasible across multiple institutions and should be further studied and made available to patients who may benefit from video-based distraction., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Miller syndrome is a rare type of postaxial acrofacial dysostosis caused by biallelic mutations in the DHODH gene, which is characterized mainly by craniofacial malformations of micrognathia, orofacial clefts, cup-shaped ears, and malar hypoplasia, combined with postaxial limb deformities like the absence of fifth digits., Methods: In this study, a prenatal case with multiple orofacial-limb abnormities was enrolled, and a thorough clinical and imaging examination was performed. Subsequently, genetic detection with karyotyping, chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) was carried out. In vitro splicing analysis was also conducted to clarify the impact of one novel variant., Results: The affected fetus displayed typical manifestations of Miller syndrome, and WES identified a diagnostic compound heterozygous variation in DHODH, consisting of two variants: exon(1-3)del and c.819 + 5G > A. We conducted a further in vitro validation with minigene system, and the result indicated that the c.819 + 5G > A variant would lead to an exon skipping in mRNA splicing., Conclusions: These findings provided with the first exonic deletion and first splice site variant in DHODH, which expanded the mutation spectrum of Miller syndrome and offered reliable evidence for genetic counseling to the affected family., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Aim: To identify metabolites, proteins, and related pathways involved in the etiology of rhegmatogenous retinal detachment (RRD) for use as biomarkers in diagnosing and treating RRD., Methods: Vitreous specimens were collected and liquid chromatography-tandem mass spectrometry analysis was performed using the four-dimensional label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, and protein interactions were analyzed., Results: Nine specimens were subjected to proteomic analysis. In total, 161 proteins were identified as differentially expressed proteins (DEPs), including 53 upregulated proteins and 108 downregulated proteins. GO functional analysis revealed that some DEPs were enriched in neuron-related terms and membrane protein terms. Moreover, KEGG analysis indicated that the cell adhesion molecule metabolic pathway was associated with the greatest number of DEPs. Finally, the evaluation of protein-protein interaction network revealed that DEPs were clustered in neuronal adhesion, apoptosis, inflammation and immune responses, correct protein folding, and glycolysis., Conclusion: Proteomic profiling is useful for the exploration of molecular mechanisms that underlie RRD. This study reveals increased expression levels of proteins related to heat shock protein content, glycolysis, and inflammatory responses in RRD. Knowledge regarding biomarkers of RRD pathogenesis may help to prevent the occurrence of RRD in the future., (International Journal of Ophthalmology Press.)

Introduction: 123 I-MIBG scan is used in neuroblastoma (NB) to monitor treatment response. Time to resolution of 123 I-MIBG avidity after radiation therapy (RT) is unknown. We sought to determine time to resolution of 123 I-MIBG avidity after RT and local failure (LF) rate., Methods: We performed a retrospective review of children with high-risk NB who underwent 123 I-MIBG scans pre- and post-RT from 2003 to 2019. Time from RT to resolution of 123 I-MIBG activity was analysed. LF and cumulative incidence of local progression (CILP) after RT stratified by site, presence of residual disease and use of boost RT were determined., Results: Forty-two patients with median age 3.9 years (1.9-4.7 years) were included, with median follow-up time 3.9 years (1.4-6.9). Eighty-six lesions were treated with RT to median dose of 21.6 Gy. Eighteen of 86 lesions were evaluable for time to resolution of MIBG avidity after RT, with median resolution time of 78 days (36-208). No LF occurred among 26 patients who received RT to primary sites after GTR, versus 4/12 (25%) patients treated with residual primary disease. 2-year CILP was 19% (12% primary disease 25% metastatic disease (P = 0.18)). 2-year CILP for non-residual primary, residual primary, non-residual metastatic and residual metastatic lesions was 0%, 42%, 11% and 30% respectively (P = 0.01) and for boosted and non-boosted residual lesions was 29% and 35% (P = 0.44)., Conclusion: Median time to MIBG resolution after RT was 78 days. Primary lesions without residual disease had excellent local control. LF rate was higher after RT for residual disease, with no benefit for boost RT., (© 2022 Royal Australian and New Zealand College of Radiologists.)

Aim: To assess the effects of intravitreal ranibizumab (IVR) on angiogenesis and glial activity of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR)., Methods: Forty-two eyes from 42 patients with PDR requiring vitrectomy were included and divided into two groups: control group ( n =16) did not receive IVR, while IVR group ( n =26) underwent IVR 5d before vitrectomy. FVM specimens were collected by the same surgeon during the interventions. Histopathological morphology was examined by hematoxylin-eosin (H-E) staining and cell densities in the FVM was assessed. Microvessels were outlined by immunohistochemical staining of CD31 and microvessel density (MVD) assessed as an index of FVM angiogenesis. Dual-color immunofluorescence staining, and confocal microscopy was used to detect co-localization and relative expression levels of glial fibrillary acidic protein (GFAP) and α-smooth muscle actin (α-SMA) as markers of glial-mesenchymal transition (GMT). The GMT index (GI; ratio of relative GFAP/α-SMA expression) was used to semi-quantify the degree of GMT or glial activity of FVMs., Results: H-E staining showed similar vascularization in both groups, with microvessels and scattered stromal cells in the matrix. Infiltrated cell densities did not differ significantly between the two groups ( P >0.05). The MVD of the IVR group (130.62±15.46/mm 2 ) was significantly lower than that of the controls (142.25±19.16/mm 2 , P <0.05). In both groups, all sections were strongly immunostained for GFAP and α-SMA. The Pearson's correlation coefficients (PCC) of intensity of automated pixel count of two markers indicated GFAP and α-SMA co-stained well and GMT participated in the remolding of FVMs in PDR. The mean relative GFAP expression in the IVR group was significantly lower, whereas that of α-SMA was significantly higher than in controls ( P <0.05). GI in the IVR group (1.10±0.10) was significantly lower than in the controls (1.21±0.12, P <0.05)., Conclusion: IVR can reduce angiogenesis, glial activity of FVM and promote glial-fibrotic transformation by reducing MVD and promoting GMT but does not decrease the cell density in patients with PDR., (International Journal of Ophthalmology Press.)

Background: Turnpenny-Fry syndrome (TPFS) has recently been defined as an uncommon monogenic disease and is characterized by global developmental delay (GDD), intellectualdisability (ID), facial dysmorphology, and skeletal abnormality. PCGF2 is the only known causative gene for TPFS, which is a component of polycomb repressive complex 1 (PRC1). PRC1 is a multi-protein complex controlling the knockdown of gene expression., Methods: The present study included the clinical evaluation of a 2.5-year-old boy with GDD and ID using cerebral MRI and the genetic testing with whole-exome sequencing. Additionally, the in silico molecular dynamic (MD) simulation was carried out on the identified variant., Results: A recurrent missense variant, namely PCGF2 : c.194C > T (p.Pro65Leu), was identified and suggested to be inherited from a mosaic father based on Sanger sequencing validation. MD results suggested a deleterious effect on the intramolecular structural flexibility and stability of PCGF2 protein by this variant., Conclusion: Our results indicated that PCGF2: p.Pro65Leu might be a hotspot for GDD and highlighted the effect of this variant on protein function., Competing Interests: None., (AJTR Copyright © 2022.)

Objective To summarize clinical characteristics and investigate possible pathogenic gene of Klippel-Feil syndrome(KFS)by the self-designed multigene panel sequencing,so as to decipher the molecular basis for early diagnosis and targeted therapy.Methods From January 2015 to December 2018,we consecutively recruited 25 patients who were diagnosed with KFS in Peking Union Medical College Hospital.The demographic information,clinical manifestations,physical examination and radiological assessments were analyzed.Multigene panel sequencing was performed after DNA extraction from peripheral blood.The possible pathogenic mutations of KFS were explored on the basis of bioinformatics analysis.Results The KFS cohort consisted of 25 patients,including 15 males and 10 females,with a mean age of(12.9±7.3)years.Limited cervical range of motion was the most common clinical feature(12 cases,48%).Based on the Samartzis classification,the proportion of patients suffered from short neck(P=0.031)and limited cervical range of motion(P=0.026)in type Ⅲ KFS was significantly higher than that in type Ⅱ and type Ⅰ KFS.Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients,including COL6A1,COL6A2,CDAN1,GLI3,FLNB,CHRNG,MYH3,POR,and TNXB.There was no pathogenic mutation found in five reported pathogenic genes(GDF6,MEOX1,GDF3,MYO18B and RIPPLY2)associated with KFS.Conclusions Our study has shown that patients with multiple contiguous cervical fusions are more likely to manifest short neck,limited cervical range of motion,and clinical triad.Therefore,these patients need additional attention and follow-up.Our analysis highlights novel KFS-related genetic variants,such as COL6A and CDAN1,extending the spectrum of known mutations contributing to this syndrome and providing a basis for elucidating the pathogenesis of KFS.

Aim: To investigate the occurrence of chronic photodamage in the cone-based retina, following long-term exposure to a 650-nm semiconductor laser (power: 2 mW)., Methods: Chickens fed for 1mo under natural light after hatching were irradiated with 650-nm laser light at different times each day. Fifteen animals were included in each group. Group A was a control group, irradiated with natural light during the entire study. Group B was irradiated with laser for 3 min/d. Group C was irradiated with laser for 6 min/d. Group D was irradiated with laser for 30 min/d. The duration of the light experiment was 6mo. We obtained data at 1, 3, and 6mo, including measuring the retinal thickness in vivo using optical coherence tomography, hematoxylin and eosin staining, TUNEL assay, apoptosis staining, malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and Western blotting to detect changes in L/M opsins and rhodopsin., Results: At 1mo, the MDA content in Group D was higher than that observed in Group A ( P =0.019). At 3mo the MDA content in Groups C and D was higher than that reported in Group A ( P =0.026, 0.003). At 6mo, the MDA content in Groups B, C, and D was higher than that observed in Group A ( P =0.038, 0.032, 0.000, respectively). There was no difference in SOD activity, and L/M opsin and rhodopsin content between the groups at 1 and 3mo. The SOD activity in group D was significantly decreased at 6mo ( P =0.000), as was the content of rhodopsin. There was no significant reduction observed in retinal thickness, abnormal cell arrangement, and positive staining of TUNEL in the groups during the 6-month study period., Conclusion: Irradiation using a 650 nm semiconductor laser (power: 2 mW) for 6min per day over 6mo do not cause photodamage. Similarly, a 3-month exposure of 30min per day do not cause damage. However, irradiation for 6mo resulted in a significant increase in the content of free radicals and a decrease in the content of rhodopsin in the retina, suggesting the presence of photodamage.

Rana kunyuensis is a species of brown frog that lives exclusively on Kunyu Mountain, Yantai, China. In the current study, a 279-bp cDNA sequence encoding a novel antimicrobial peptide (AMP), designated as amurin-9KY, was cloned from synthesized double-strand skin cDNA of R. kunyuensis. The amurin-9KY precursor was composed of 62 amino acid (aa) residues, whereas the mature peptide was composed of 14 aa and contained two cysteines forming a C-terminal heptapeptide ring (Rana box domain) and an amidated C-terminus. These structural characters represent a novel amphibian AMP family. Although amurin-9KY exhibited high similarity to the already identified amurin-9AM from R. amurensis, little is known about the structures and activities of amurin-9 family AMPs so far. Therefore, amurin-9KY and its three derivatives (amurin-9KY1-3) were designed and synthesized. The structures and activities were examined to evaluate the influence of C-terminal amidation and the heptapeptide ring on the activities and structure of amurin-9KY. Results indicated that C-terminal amidation was essential for antimicrobial activity, whereas both C-terminal amidation and the heptapeptide ring played roles in the low hemolytic activity. Circular dichroism (CD) spectra showed that the four peptides adopted an a-helical conformation in THF/H2O (v/v 1:1) solution, but a random coil in aqueous solution. Elimination of the C-terminal heptapeptide ring generated two free cysteine residues with unpaired thiol groups, which greatly increased the concentration-dependent anti-oxidant activity. Scanning electron microscopy (SEM) was also performed to determine the possible bactericidal mechanisms.