Origin of quantum ring formation during droplet epitaxy.

Droplet epitaxy of GaAs is studied in real time using in situ surface electron microscopy. The resulting movies motivate a theoretical model for quantum ring formation which can explain the origin of nanoscale features such as double rings observed under a variety of experimental conditions. Inner rings correspond to GaAs deposition at the droplet edge, while outer rings result from the reaction of Ga and As atoms diffusing along the surface. The observed variety of morphologies primarily reflects relative changes in the outer rings with temperature and As flux.

[Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes].

Objective: To investigate the molecular etiology of Perrault syndrome by analyzing the clinical phenotype and pathogenic gene variants of 2 male patients with bilateral severe sensorineural deafness. Methods: Two male patients with Perrault syndrome characterized by severe sensonrineual deafness adimitted to the First Affiliated Hospital of Zhengzhou University between February 2021 and March 2022 were selected, and the clinical phenotype and pathogenic gene variants of them and their family members were summarized. The whole exome sequencing technology was used to screen the pathogenic variants of the probands, and the candidate variants were determined by combining with clinical phenotype. The probands and their family members were verified by the Sanger sequencing method. Results: The whole exome sequencing results showed that the proband of family 1 had a compound heterozygous variants of the LARS2 (NM_015340.4) gene c.1565C>A (p.Thr522Asn) and c.1079T>C (p.Ile360Thr). The reported pathogenic variant c.1565C>A came from the mother, and the novel variant c.1079T>C came from the father. The second proband harbored compound heterozygous variants of HARS2 gene (NM_012208.4) c.1273C>T (p.Arg425Trp) and c.1403G>C (p.Gly468Ala), with the former from the proband's mother, the latter from the father. The c.1273C>T was novel and c.1403G>C was the reported pathogenic variant. All above variants were respectively classified as pathogenic, uncertain significance, uncertain significance and likely pathogenic based on the ACMG guidelines. Conclusion: This study expands the mutational spectrum of LARS2 and HARS2 genes, which highlights that genetic testing plays an important role in the early diagnosis of syndromic deafness.

[Branchio-oto-renal syndrome or branchio-oto syndrome: the clinical and genetic analysis in five Chinese families].

Objective: To screen the causative genes of five families with branchio-oto-renal syndrome (BORS) or branchio-oto syndrome(BOS) and to analyze the phenotypic characteristics and clinical management strategies of patients. Methods: Five families with BORS/BOR from December 2018 to September 2021 were recruited, information of patients, including family history and medical history, was collected, and genealogies were drawn. The examinations concerning audiology, nephrology, and radiology were performed on the affected individuals. Peripheral blood was obtained for DNA extraction, then next-generation sequencing technology was used to screen candidate variants associated with BORS/BOS. Based on patient's clinical results, the appropriate interventions were recommended and implemented. Results: Eight individuals were diagnosed with BOS or BORS. Of the eight patients, all had hearing loss, preauricular pits and ear malformations, and only four presented with branchial cleft fistulae or cysts. Except for two patients(5-I-2, 5-II-2) who did not undergo renal examination, the remaining six lacked renal abnormalities. Genetic analysis identified four likely pathogenic or pathogenic EYA1 variants (c.1715G>T, c.1140+1G>A, c.639G>C, c.1475+1G>C; NM_000503.6), and c.1715G>T was first reported in this study. Middle ear ossicular reconstruction was performed in 1-II-2,2-I-2 and 3-II-2, but did not yield the expected results; then hearing aids and cochlear implantation were recommended and achieved satisfactory results. Conclusions: Next-generation sequencing technology facilitates the diagnosis and genetic counseling of BORS/BOS. Hearing loss, preauricular pits, ear malformations and branchial cleft fistulae or cysts are the most common manifestations of patients in this study. Middle ear surgeries for improving hearing loss may have some limitations in BORS/BOS patients, and hearing aids and cochlear implantation can contribute to hearing gains.

Elementary excitations at magnetic surfaces and their spin dependence.

The elementary surface excitations are studied by spin-polarized electron energy loss spectroscopy on a prototype oxide surface [an oxygen passivated Fe(001)-p(1×1) surface], where the various excitations coexist. For the first time, the surface phonons and magnons are measured simultaneously and are distinguished based on their different spin nature. The dispersion relation of all excitations is probed over the entire Brillouin zone. The different phonon modes observed in our experiment are described by means of ab initio calculations.

Decomposition controlled by surface morphology during langmuir evaporation of GaAs.

When GaAs is heated in vacuum, it decomposes into Ga and As as it evaporates. Real-time in situ surface electron microscopy reveals striking bursts of "daughter" droplet nucleation and growth when coalescence of large "parent" droplets exposes nonplanar surface regions. We analyze the behavior, predicting a morphology-dependent congruent evaporation temperature. Based on this we propose a new approach for the self-assembly and positioning of quantum structures via droplet epitaxy, which we demonstrate at the proof-of-concept level.

Asymmetric spin-wave dispersion on Fe(110): direct evidence of the Dzyaloshinskii-Moriya interaction.

The influence of the Dzyaloshinskii-Moriya interaction on the spin-wave dispersion in an Fe double layer grown on W(110) is measured for the first time. It is demonstrated that the Dzyaloshinskii-Moriya interaction breaks the degeneracy of spin waves and leads to an asymmetric spin-wave dispersion relation. An extended Heisenberg spin Hamiltonian is employed to obtain the longitudinal component of the Dzyaloshinskii-Moriya vectors from the experimentally measured energy asymmetry.

[Study on syndromic deafness caused by novel pattern of compound heterozygous variants in the CDH23 gene].

Objective: To explore the pathogenic variants of a family with syndromic deafness by high-throughput sequencing. Methods: The family was from Puyang City, Henan Province, and had four members, including two with syndromic deafness. The proband and his sister had congenital deafness, and their parents had normal phenotypes. The clinical phenotype of the family was characterized using clinical examinations and pedigree analysis. The clinical examinations included imaging examination, audiometry (pure tone audiometry, acoustic immittance, brainstem auditory evoked potential, and otoacoustic emission), vestibular function test, and ophthalmic examination (visual acuity test, visual field test, fundus examination, visual evoked potential, and electroretinogram). Target exome sequencing of 129 known deafness genes and bioinformatics analysis were used to screen suspected pathogenic variants. Sanger sequencing and minigene assay were used to verify and functionally investigate the mutation detected, respectively. According to the standards and guidelines for interpreting genetic variants proposed by the American College of Medical Genetics and Genomics, the variants c.6049G>A and c.8699A>G were classified as pathogenic/likely pathogenic, and the variant c.9856C>G was classified as variants of uncertain significance. Results: The probands and his sister had severe sensorineural hearing loss with decreased binocular vision, night blindness, decreased peripheral visual field sensitivity and partial visual field defect, and normal vestibular function. Both of them had three CDH23 mutations, including CDH23 (NM_022124.5) c.6049G>A (p.Gly2017Ser),c.9856C>G (p.His3286Asp), and c.8699A>G (p. Asp2900Gly), The first two were inherited from the father, and the last one was from the mother. The missense variants c.9856C>G and c.8699A>G were not included in the gnomad database. The missense mutation c.6049G>A was located in the last position of exon 46 and was predicted to affect splicing by bioinformatics software. The minigene experiment showed that the mutation cause exon skipping of exon 46, resulting in an abnormal protein. Conclusions: Compound heterozygous variations of the CDH23 are the leading cause of USH1D in the family. This study confirms that the compound heterozygosity of splicing and missense variants of the CDH23 gene could lead to USH1D.

A randomized controlled trial of high-permeability haemodialysis against conventional haemodialysis in the treatment of uraemic pruritus.

BACKGROUND: Uraemic pruritus (UP) is one of the most common problems in patients with chronic renal failure. Owing to the complexity of UP, no specific treatment is currently available. Recently, the accumulated toxins of mid and macro molecules in advanced renal failure have been proposed to play an important role in the mediation of pruritus. AIM: To evaluate the effect of high permeability haemodialysis (HPHD) against conventional haemodialysis (CHD) on UP. METHODS: A randomized, prospective, double-blind study was performed to compare the efficacy of HPHD against CHD in the treatment of UP. In total, 116 patients with chronic renal failure and UP were enrolled in the trial. A visual analogue scale (VAS) was used to assess the severity of itch. The toxins of mid and macro molecules [beta2-microglobulin (beta2-MG), parathyroid hormone (PTH), respectively] were measured, and the solute clearance rate (SCR) and urea clearance index (Kt/V) were also determined. RESULTS: The pruritus scores in the HPHD group were significantly lower (2.23 +/- 1.05) than those in the CHD group (5.45 +/- 1.91, P = 0.012), although the SCR and Kt/V showed no significance between the two groups (SCR P = 0.075; Kt/V P = 0.082). It was found that HPHD and CHD achieved a reasonable clearance rate of blood urea nitrogen and creatinine. However, the toxins of mid and macro molecules were markedly reduced in the blood of patients treated with HPHD, compared with those treated with CHD. The concentrations of PTH and beta2-MG were significantly reduced by HPHD in comparison with CHD (PTH 119.27 +/- 8.41 vs. 165.18 +/- 9.37 pmol/L, P = 0.01; beta2-MG 3.39 +/- 0.76 vs. 5.92+/- 1.58 g/mL, P = 0.012). CONCLUSIONS: These data indicate that HPHD can efficiently relieve UP through clearance of accumulated mid and macro molecules in vivo. This further supports the hypothesis that these molecules are involved in UP.

Ga droplet morphology on GaAs(001) studied by Lloyd's mirror photoemission electron microscopy.

We apply Lloyd's mirror photoemission electron microscopy (PEEM) to study the surface shape of Ga droplets on GaAs(001). An unusual rectangular-based droplet shape is identified and the contact angle is determined in situ. It is shown that quenching does not appreciably affect droplet shape and ex situ measurements of the contact angle by atomic force microscopy are in good agreement with Lloyd's mirror PEEM. Extension of Lloyd's mirror technique to reconstruct general three-dimensional (3D) surface shapes and the potential use of synchrotron radiation to improve vertical resolution is discussed.

[The study of AAV9 expression in cochleae of mice at different ages].

Objective: To determine the extent of transfection and expression of adeno-associated virus (AAV) serotype 9 (AAV9) in the cochleae of mice at different ages. Methods: AAV9-green fluorescent protein (GFP) was inoculated into the cochlea of mice via the round window membrane (RWM) or through cochleostomy at different ages. Four groups were divided according to ages and injection sites: P1SM group, AAV9-GFP was delivered to the scala media by cochleostomy at postnatal day 1; P1RW group, AAV9-GFP was delivered to the scala tympani via RWM at postnatal day 1; P9RW group: AAV9-GFP was injected through RWM at postnatal day 9; and P30RW group, adult mice (P30) were injected through RWM. GFP expression in cochlear whole mount was analyzed and auditory brainstem response (ABR) tests were conducted one month after virus injection (for each animal, only left cochlea was injected and the right side was used as a control). GraphPad Prism 5 statistical software was used for data analysis. Results: All of inner hair cells (IHCs) and most of outer hair cells (OHCs) were transfected via two approaches at P1 injection. There was no significant difference in ABR threshold between injected ears and untreated ears (P>0.05). All of the IHCs and parts of OHCs (69% in apical turn) were transfected via RWM at P9. The strongest GFP expression was observed near the apical turn. Cochlear inoculation via RWM at P30 led to transgene expression in only IHCs. The ABR threshold of injected ears in P9RW group and P30RW group was significantly higher than that of contralateral ears (P<0.01). Conclusions: AAV9 can be highly expressed in the inner and outer hair cells of the cochlea and hearing sensitivity can be preserved if virus injections are performed in neonatal mice. After AAV9 is transfected into the inner ear of adult mice, it is only expressed in the inner hair cells, which leads to the increase of the ABR response threshold of mice. Transfection efficiency is significant higher in neonate mice than in P9 and adult mice.

ARL 17477, a potent and selective neuronal NOS inhibitor decreases infarct volume after transient middle cerebral artery occlusion in rats.

We tested the effects of administration of a selective neuronal nitric oxide synthase (nNOS) inhibitor, ARL 17477, on ischemic cell damage and regional cerebral blood flow (rCBF), in rats subjected to transient (2 h) middle cerebral artery (MCA) occlusion and 166 h of reperfusion (n = 48) and in rats without MCA occlusion (n = 25), respectively. Animals were administered ARL 17477 (i.v.): 10 mg/kg; 1 mg/kg; 3mg/kg; N-nitro-L-arginine (L-NA) 10 mg/kg L-NA 1 mg/kg; and Vehicle. Administration of ARL 17477 1 mg/kg, 3 mg/kg and 10 mg/kg reduced ischemic infarct volume by 53 (p < 0.05), 23, and 6.5%, respectively. L-NA 1 mg/kg and 10 mg/kg increased infarct volume by 2 and 15%, respectively (p > 0.05). Administration of ARL 17477 (10 mg/kg) significantly (p < 0.05) decreased rCBF by 27 +/- 5.3 and 24 +/- 14.08% and cortical NOS activity by 86 +/- 14.9 and 91 +/- 8.9% at 10 min or 3 h, respectively, and did not alter mean arterial blood pressure (MABP). L-NA (10 mg/kg) significantly reduced rCBF by 23 +/- 9.8% and NOS activity by 81 +/- 7% and significantly (p < 0.05) increased MABP. Treatment with 3 mg/kg and 1 mg/kg ARL 17477 reduced rCBF by only 2.4 +/- 4.5 and 0%, respectively, even when NOS activity was reduced by 63 +/- 13.4 and 45 +/- 15.7% at 3 h, respectively, (p < 0.05). The data demonstrate that ARL 17477 inhibits nNOS in the rat brain and causes a dose-dependent reduction in infarct volume after transient MCA occlusion.

Synthetic peptide derived from the Bordetella pertussis bacterium reduces infarct volume after transient middle cerebral artery occlusion in the rat.

We explored the therapeutic potential of a peptide (F20) derived from the filamentous hemagglutinin of Bordetella pertussis in a model of ischemic cell injury after transient (2 hours) middle cerebral artery (MCA) occlusion in the rat. Animals were divided into two groups-(1) F20 peptide group: rats (n = 11) were subjected to 2 hours of transient MCA occlusion, and F20 peptide was administered intravenously (50 nmol) at 0 hours of reperfusion and intraperitoneally (150 nmol/dose) at 2, 4, 6, 8, 22, and 30 hours of reperfusion; (2) control group: rats (n = 10) were administered peptide F23 (a scrambled version of peptide F20) with the same experimental protocol as the F20 peptide group. Forty-six hours after reperfusion, animals were sacrificed, and brain tissue was stained with triphenyltetrazolium chloride for evaluation of tissue damage. To measure neutrophil numbers in ischemic tissue, myeloperoxidase (MPO) immunostaining was performed on a coronal cerebral section in each animal. There was a significant reduction of ischemic infarct volume (36%, p < 0.05) in the F20 group of animals compared with the F23 group. The area of the ischemic lesion was highly correlated with the numbers of the immunoreactive MPO cells (r = 0.78, p < 0.001). The data demonstrate that the F20 peptide significantly reduces infarct volume and intraparenchymal neutrophil numbers after transient MCA occlusion.

Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues.

PURPOSE: To localize pigment epithelium-derived factor (PEDF) in developing and adult human ocular tissues. METHODS: PEDF was localized in fetal and adult eyes by immunofluorescence with a polyclonal antibody (pAb) against amino acids 327-343 of PEDF, or a monoclonal antibody (mAb) against the C-terminal 155 amino acids of PEDF. Specificity of the antibodies was documented by Western blotting. PEDF mRNA was localized in adult retina by in situ hybridization. RESULTS: In developing retinas (7.4 to 21.5 fetal weeks, Fwks), pAb anti-PEDF labeled retinal pigment epithelium (RPE) granules, developing cones, some neuroblasts and many cells in the ganglion cell layer (GCL). In adult retinas, pAb anti-PEDF labeled rod and cone cytoplasm and nuclei of rods but not cones. Cells in the INL and GCL, choroid, corneal epithelium and endothelium, and ciliary body were also pAb PEDF-positive. Preadsorption of pAb anti-PEDF with the immunizing peptide blocked specific labeling in retina and other tissues, except for photoreceptor outer segments. In agreement with the immunolocalization with pAb anti-PEDF, in situ hybridization revealed PEDF mRNA in the RPE, photoreceptors, inner nuclear layer cells and ganglion cells in adult retina. In developing retinas 18 Fwks and older, and in adult retinas, mAb anti-PEDF labeled the interphotoreceptor matrix (IPM). Western blots of retina, cornea, and ciliary body/iris with pAb anti-PEDF produced several bands at about 46 kDa. With mAb anti-PEDF, retina produced one band at about 46 kDa; cornea and ciliary body/iris had several bands at about 46 kDa. CONCLUSIONS: PEDF, originally reported as a product of RPE cells, is present in photoreceptors and inner retinal cell types in developing and adult human eyes. Photoreceptors and RPE may secrete PEDF into the IPM.

Individual pineal cells exhibit a circadian rhythm in melatonin secretion.

Pineal glands and dissociated pineal cells exhibit a circadian rhythm of melatonin secretion in vitro which persists for several cycles under constant conditions. It is not known whether individual, physically isolated pineal cells are capable of generating a circadian oscillation in melatonin release. This question was addressed by utilizing a reverse hemolytic plaque assay for the detection of melatonin secretion from individual pineal cells. Dissociated pineal cells from the anole lizard, maintained in short term culture, displayed a marked variation in melatonin secretion for up to 72 h under both cyclic lighting conditions and in constant dark. The persistence of daily fluctuations of melatonin secretion from individual cells strongly suggests that individual pineal cells can function as circadian oscillators.

Postischemic treatment (2-4 h) with anti-CD11b and anti-CD18 monoclonal antibodies are neuroprotective after transient (2 h) focal cerebral ischemia in the rat.

We investigated the effects of F(ab')2 fragments of anti-CD11b and anti-CD18 monoclonal antibodies on ischemic cell damage in the rat when administered upon reperfusion and at 2 h of reperfusion after transient (2 h) middle cerebral artery (MCA) occlusion. 2 h of MCA occlusion was induced by intraluminal insertion of a monofilament. The following groups of animals were investigated. Anti-CD11b groups (n = 15): an intact anti-CD11b antibody (1B6c) and an anti-CD11b F(ab')2 fragment of 1B6c were infused upon reperfusion (4 mg/kg i.v.). Anti-CD18 group (n = 8): an anti-CD18 F(ab')2 fragment of CL26 was infused upon reperfusion (2 mg/kg i.v.), and at 22 h of reperfusion (1 mg/kg i.v.). Anti-CD11b delayed group (n = 9): an anti-CD11b F(ab')2 fragment of 1B6c was infused at 2 h of reperfusion (4 mg/kg i.v.), and at 22 h after reperfusion (2 mg/kg i.v.). Control groups (n = 18): an isotype-matched control antibody (mouse IgG1) was administered: (a) upon reperfusion (n = 13), and (b) at 2 h and 22 h of reperfusion (n = 5). Rats were sacrificed at 7 days of reperfusion. In a separate population of rats subjected to 2 h of MCA occlusion (n = 9), brain myeloperoxidase (MPO) activity was measured at 46 h of reperfusion. The vehicle groups had infarct volumes of 35.21 +/- 2.82% to 41.39 +/- 2.73% of the contralateral hemisphere, respectively. Infarct volume was significantly reduced after treatment with: the intact anti-CD11b antibody upon reperfusion (19.0 +/- 6.6%) (P < 0.05), the fragments of mAbs of anti-CD11b administered upon reperfusion (19.7 +/- 2.7%) (P < 0.05), and at 2 h of reperfusion (22.2 +/- 4.8%) (P < 0.05), and anti-CD18 administered upon reperfusion (20.4 +/- 4.8%) (P < 0.05). Anti-CD11b treatment significantly (P < 0.05) inhibited the increase of MPO activity in the ischemic hemisphere. Our data demonstrate that anti-CD11b and anti-CD18 mAb fragments significantly reduce infarct volume and inhibit the increase of MPO activity in the ischemic lesion; administration of anti-CD11b mAb fragment even at 2 h of reperfusion significantly reduces infarct volume. These data support importance of the beta 2 integrin CD11b/CD18 in ischemia/reperfusion injury and indicate that the therapeutic window for intervention to reduce ischemic cell damage in this model is at least 4 h from the onset of MCA occlusion.

The temporal profiles of ICAM-1 protein and mRNA expression after transient MCA occlusion in the rat.

Leukocytes may contribute to ischemic cell damage. ICAM-1 expression on endothelial cells facilitates the migration of leukocytes into tissue. Therefore, we measured the temporal profiles of ICAM-1 mRNA and protein in rat brain after transient (1 or 2 h) of middle cerebral artery (MCA) occlusion. Male Wistar rats (n = 86) were subjected to 1 or 2 h MCA of occlusion, or 2 h of MCA occlusion followed by reperfusion for a variety of durations ranging from 1 h to 1 week. 10 additional control animals were employed. ICAM-1 mRNA and protein were measured during ischemia and reperfusion, and immunohistochemical methods were used to identify specific cell types expressing ICAM-1. ICAM-1 mRNA was detected 1 h after the onset of ischemia. mRNA maximized at 10 h of reperfusion and persisted out to 1 week of reperfusion. ICAM-1 significantly increased in microvascular endothelial cells at 2 h of reperfusion, maximized at 46 h and persisted out to 1 week of reperfusion (P < 0.05). ICAM-1 mRNA and protein are present in ischemic brain early after the onset of ischemia and reperfusion, respectively. These data provide support for the role of ICAM-1 in mediating leukocyte-endothelial adhesion after transient MCA occlusion in the rat.

Pineal photoreceptors rhythmically secrete melatonin.

Individual pineal cells secrete melatonin with a circadian period, reducing a vertebrate circadian system to the level of a single cell [Brain Res., 627 (1993) 141-146]. In the present study, dissociated pineal cells were identified as melatonin-secreting by a reverse hemolytic plaque assay (RHPA) and all melatonin-secreting cells were immuno-positive when analyzed for the photoreceptor protein S-antigen. The results are the first direct evidence that isolated photoreceptor cells secrete melatonin and taken together with our previous findings indicate that single pineal cells contain: (1) a circadian oscillator; (2) a photoreceptive capacity; and (3) the ability to secrete melatonin rhythmically.

Studies on structures of some platinum complexes with 1,1-cyclopropanedicarboxylate.

The crystal structures of [Pt(NH3)2CPrDCA].H2O (I), [Pt(CH3NH2)2CPrDCA] (II), and [Pt(dmbn) CPrDCA].2.5H2O (III) (where CPrDCA is 1,1-cyclopropanedicarboxylate; dmbn is 2,3-dimethyl-2,3-butyldiamine) are determined. Compound I crystallizes in the orthorhombic space group Pnma with the cell dimensions: a = 6.517(2), b = 9.709(3), c = 14.205(5) A, Z = 4, R = 0.058. Compound II is monoclinic with space group P2(1)/n, a = 9.648(3), b = 8.720(2), c = 12.770(4) A, beta = 107.12(2), Z = 4, R = 0.059. Compound III belongs to the monoclinic system space group P2(1)/m with the cell dimensions: a = 6.494(1), b = 19.638(3), c = 6.606(1)A, beta = 94.44(1), Z = 2, R = 0.038. Electronic structures of the complexes are studied and the correlation between structure of the amine ligands and biological activity of the complexes is explored.

Caustic imaging of gallium droplets using mirror electron microscopy.

We discuss a new interpretation of mirror electron microscopy (MEM) images, whereby electric field distortions caused by surface topography and/or potential variations are sufficiently large to create caustics in the image contrast. Using a ray-based trajectory method, we consider how a family of rays overlaps to create caustics in the vicinity of the imaging plane of the magnetic objective lens. Such image caustics contain useful information on the surface topography and/or potential, and can be directly related to surface features. Specifically we show how a through-focus series of MEM images can be used to extract the contact angle of a Ga droplet on a GaAs (001) surface.