Focal choroidal excavation: a preliminary interpretation based on clinic and review

AIM: To describe the clinical and imaging characteristics associated with focal choroidal excavation(FCE), analyze the possible complication, and interpret its probable etiopathogenesis.METHODS: Retrospective descriptive case series of 37 eyes of 32 patients with FCE. Findings of spectral-domain optical coherence tomography(SD-OCT),fluorescein angiography, indocyanine green angiography,and clinical features were analyzed. RESULTS: All patients were Chinese. Five patients(15.6%) were bilaterally involved. Patients’ ages ranged from 7 to 66 y. Refractive error ranged between +2.0 D and 11.0 D. Mean best-corrected visual acuity was 0.6(range, 0.1 to 1.2). Fundus examinations exhibited mild-moderate localized pigmentary disturbances in the corresponding area of 17 eyes. Fluorescein angiography performed in 18 patients showed varying degrees of hyperfluorescence and hypofluorescence related to a range of retinal pigment epithelium(RPE) alterations.Indocyanine green angiography performed in 7 patients showed hypofluorescence at the excavation. SD-OCT demonstrated choroidal excavation in all 37 eyes.Twenty-nine eyes showed a single lesion of FCE, and three eyes showed 2-3 separated lesions. Fifteen eyes showed separation between the photoreceptor tips andRPE consistent with nonconforming FCE. Central serous chorioretinopathy(CSC, n =1) and choroidal neovascularization(CNV, n =1) developed during follow-up.CONCLUSION: FCE could be interpreted as congenital focal choroidal dysplasia involving the RPE,choriocapillaris, and photoreceptor associated with the faulty anatomy. The abnormal anatomy of FCE was similar to anatomy at risk of CSC and CNV.

Simultaneously measuring ocular aberration and anterior segment biometry during accommodation

In the human eye,accommodation is essential for functional vision.However,the mechanisms regulating accommodation and the ocular parameters afcting aberrations remain to be ex-plored.In order to measure the alterations of ocular aberration and crystalline lens biometry during dynamic acoommodative stimuli,we designed an optical coberence tomography with ultra-long penetration depth(UL-OCT)combined with a Shack-Hartmann wavefront sensor(SHWFS).This integrated set up measures human eye's anterior segment as well as mono-chromatie high-order aberrations(HOAs)with 6 um resolution and(1/20)λaccuracy.A total of 10 healthy volunteers without ocular diseases were examined.Upon exposure to accommodative stimuli,the wavefront aberrations became larger.Among the anterior segment biometry,the anterior crystalline lens demonstrated significant curvature during accommodation and was the major cause of high-order aberration.These findings suggest that the front surface of the crys-talline lens can siguificantly affect variation among aberrations,which is a key factor underlying the quality of human vision.

More severe toxicity of gold nanoparticles with rougher surface in mouse hippocampal neurons

Gold nanoparticles(GNPs)have been extensively used in nanomedicine and neuroscience owing to their biological inertness,peculiar opto-electronic and physico-chemical features.However,the effect of GNPs shape on the neurophysiological properties of single neuron is still unclear.To tackle this issue,different shape GNPs(nanosphere,nanotriakisoctahedron and nanoflower)were synthesized to investigate the effect of GNPs on the voltage-dependent sodium channel and the action potential(AP)of hippocampal CA1 neurons in mice.The results indicated that GNPs inhibited the amplitudes of voltage-gated sodium current(I_(Na))and led to a hyperpolarizing shift in the voltage-dependence curve of both activation and inactivation of I_(Na).GNPs also increased neuronal excitability and altered some properties of AP.Moreover,most alterations in AP properties were observed in nanoflower GNPs treated CA1 neurons,suggesting that the neurotoxicity of gold nanoparticles is surface roughness-dependent.These results may provide a valuable direction in the clinical application of GNPs.

Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy

BET proteins,which influence gene expression and contribute to the development of cancer,are epigenetic interpreters.Thus,BET inhibitors represent a novel form of epigenetic anticancer treatment.Although preliminary clinical trials have shown the anticancer potential of BET inhibitors,it appears that these drugs have limited effectiveness when used alone.Therefore,given the limited monotherapeutic activity of BET inhibitors,their use in combination with other drugs warrants attention,including the meaningful variations in pharmacodynamic activity among chosen drug combinations.In this paper,we review the function of BET proteins,the preclinical justification for BET protein targeting in cancer,recent advances in small-molecule BET inhibitors,and preliminary clinical trial findings.We elucidate BET inhibitor resistance mechanisms,shed light on the associated adverse events,investigate the potential of combining these inhibitors with diverse therapeutic agents,present a comprehensive compilation of synergistic treatments involving BET inhibitors,and provide an outlook on their future prospects as potent antitumor agents.We conclude by suggesting that combining BET inhibitors with other anticancer drugs and innovative next-generation agents holds great potential for advancing the effective targeting of BET proteins as a promising anticancer strategy.

Entrainment of Astrocytic and Neuronal Ca^(2+) Population Dynamics During Information Processing of Working Memory in Mice

Astrocytes are increasingly recognized to play an active role in learning and memory,but whether neural inputs can trigger event-specific astrocytic Ca^(2+)dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca^(2+)dynamics in animals performing tasks.Here,using fiber photometry,we showed that population astrocytic Ca^(2+)dynamics in the hippocampus were gated by sensory inputs(centered at the turning point of the T-maze)and modified by the reward delivery during the encoding and retrieval phases.Notably,there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca^(2+)dynamics with a 3-s phase difference.Furthermore,there was a robust synchronization of astrocytic Ca^(2+)at the population level among the hippocampus,medial prefrontal cortex,and striatum.The inter-locked,bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.

Drosophila heparan sulfate 3-0 sulfotransferase B Null Mutant Is Viable and Exhibits No Defects in Notch Signaling

Heparan sulfate proteoglycans （HSPGs） are critically involved in a variety of biological events. The functions of HSPGs are determined by the nature of the core proteins and modifications of heparan sulfate （HS） glycosaminoglycan （GAG） chains. The distinct O-sulfo- transferases are important for nonrandom modifications at specific positions. Two HS 3-0 sulfotransferase （Hs3st） genes, Hs3st-A and Hs3st-B, were identified in Drosophila. Previous experiments using RNA interference （RNAi） suggested that Hs3st-B was required for Notch signaling. Here, we generated a null mutant of Hs3st-B via ends-out gene targeting and examined its role（s） in development. We found that homozygous Hs3st-B mutants have no neurogenic defects or alterations in the expression of Notch signaling target gene. Thus, our results strongly argue against an essential role for Hs3st-B in Notch signaling. Moreover, we have generated two independent Hs3st-A RNAi lines which worked to deplete Hs3st-A. Importantly, Hs3st-A RNAi combined with Hs3st-B mutant flies did not alter the expression of Notch signaling components, arguing that both Hs3st-A and Hs3st-B were not essential for Notch signaling. The establishment of Hs3st-B mutant and effective Hs3st-A RNAi lines provides essential tools for further studies of the physiological roles of Hs3st-A and Hs3st-B in development and homeostasis.

Adverse events of intravenous immunoglobulin infusions:a three-year retrospective study in China

Intravenous immunoglobulin(IVIG) is biological product, which is extensively used in pediatric patients, with high adverse effects on children among different brand preparations. In the present study, we aimed to describe the adverse events of pediatric patients given IVIG infusions in China. Data were collected from all patients receiving IVIG infusion at the largest children’s hospital in Ningbo of China form January 2015 to December 2017. Descriptive statistics was used. A total of 2100 patients received IVIG infusion. All the patients who experienced adverse reactions were children(0.48%), with the highest frequency of infusion among those age 1 to 3 years old(40%). Among 10 infusions with adverse reactions, the most common indication was Kawasaki disease(40%) followed by severe pneumonia(30%). Rash was the most common adverse event(80%), followed by chest pain & cough(50%) and cyanosis(40%). Adverse events were observed to occur most frequently within 30 min from onset of infusion. Most of the reactions occurred with the large dose and the indications of used for. Since the hospital changed the brand, the incidence of adverse reactions was decreased from 1.39% to 0.13%. In this study, 0.48% of pediatric patients given IVIG infusions experienced adverse events. Anaphylactoid reaction was the most common manifestation. Symptoms occurred within 30 min from onset of infusion, which were affected by the dose, the value of lgE, the indications and the different brands.

Fast segmentation of anterior segment optical coherence tomography images using graph cut

Background:Optical coherence tomography(OCT)is a non-invasive imaging system that can be used to obtain images of the anterior segment.Automatic segmentation of these images will enable them to be used to construct patient specific biomechanical models of the human eye.These models could be used to help with treatment planning and diagnosis of patients.Methods:A novel graph cut technique using regional and shape terms was developed.It was evaluated by segmenting 39 OCT images of the anterior segment.The results of this were compared with manual segmentation and a previously reported level set segmentation technique.Three different comparison techniques were used:Dice’s similarity coefficient(DSC),mean unsigned surface positioning error(MSPE),and 95%Hausdorff distance(HD).A paired t-test was used to compare the results of different segmentation techniques.Results:When comparison with manual segmentation was performed,a mean DSC value of 0.943±0.020 was achieved,outperforming other previously published techniques.A substantial reduction in processing time was also achieved using this method.Conclusions:We have developed a new segmentation technique that is both fast and accurate.This has the potential to be used to aid diagnostics and treatment planning.

In vivo imaging of mice auricle vessels using adaptive optical confocal fluorescence microscope

Facilitated with stochastic parallel gradient descent(SPGD) algorithm for wavefront sensorless correcting aberrations, an adaptive optics(AO) confocal fluorescence microscopy is developed and used to record fluorescent signals in vivo. Vessels of mice auricle at 80, 100 and 120 μm depth are obtained, and image contrast and fluorescence intensity are significantly improved with AO correction. The typical 10%–90% rise-time of the metric value measured is 5.0 s for a measured close-loop bandwidth of 0.2 Hz. Therefore, the AO confocal microscopy implemented with SPGD algorithm for robust AO corrections will be a powerful tool for study of vascular dynamics in future.

Progressive cracking technique for phacoemulsification of superhard cataracts: a case report

Background:Complete nuclear disassembly of superhard cataracts cannot always be achieved by phaco chop,which is considered one of the best techniques for dealing with hard cataracts.We present a phaco chopprogressive cracking technique to divide superhard cataracts completely.Case presentation:We presented a case of cataract with over Grade V nucleus sclerosis and very low density of corneal endothelial cell(812 cells/mm^(2)).By performing the cataract surgery with our phaco chop-progressive cracking technique,the corneal endothelial cells were well protected and the patient’s visual acuity was markedly improved from finger counting at 40 cm to 20/200 the day after surgery without obvious corneal edema.Conclusions:Although an initial learning curve was needed,this phaco chop-progressive cracking technique could be of particular benefit to the superhard cataract,especially in patients with low density of corneal endothelial cells.

Folate/Vitamin B Alleviates Hyperhomocysteinemia-Induced Alzheimer-Like Pathologies in Rat Retina

Hyperhomocysteinemia(Hhcy) is an independent risk factor for Alzheimer's disease(AD). Visual dysfunction is commonly found and is positively correlated with the severity of cognitive defects in AD patients. Our previous study demonstrated that Hhcy induces memory deficits with AD-like tau and amyloid-b(Ab) pathologies in the hippocampus, and supplementation with folate and vitamin B12(FB) prevents the Hhcy-induced AD-like pathologies in the hippocampus. Here, we investigated whether Hhcy also induces AD-like pathologies in the retina and the effects of FB. An Hhcy rat model was produced by vena caudalis injection of homocysteine for14 days, and the effects of FB were assessed by simultaneous supplementation with FB in drinking water. We found that Hhcy induced vessel damage with Ab and taupathologies in the retina, while simultaneous supplementation with FB remarkably attenuated the Hhcy-induced tau hyperphosphorylation at multiple AD-related sites and Ab accumulation in the retina. The mechanisms involved downregulation of amyloid precursor protein(APP), presenilin-1, beta-site APP-cleaving enzyme 1, and protein phosphatase-2 A. Our data suggest that the retina may serve as a window for evaluating the effects of FB on hyperhomocysteinemia-induced Alzheimer-like pathologies.

The Sterile 20-Like Kinase Tao Controls Tissue Homeostasis by Regulating the Hippo Pathway in Drosophila Adult Midgut

The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. However, the regulation of stem cell proliferation and differentiation is not fully understood. Here we show that the sterile-like 20 kinase, Tao, controls tissue homeostasis by regulating the Hippo pathway in the Drosophila adult midgut. Depletion of Tao in the progenitors leads to rapid intestinal stem cell （ISC） proliferation and midgut homeostasis loss. Meanwhile, we find that the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling activity and cytokine production are significantly increased, resulting in stimulated ISC proliferation. Furthermore, expression of the Hippo pathway downstream targets, Diapl and bantam, is dramatically increased in Tao knockdown intestines. Consistently, we show that the Yorkie （Yki） acts downstream of Tao to regulate ISC proliferation. Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control.

Common Postzygotic Mutational Signatures in Healthy Adult Tissues Related to Embryonic Hypoxia

Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clocklike mutational processes,and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles.Notably,signature C,characterized by C>T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6%of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites;and individuals’genetic background may also influence their postzygotic mutation profiles.