Optical Coherence Tomography Angiography Reveals Distinct Retinal Structural and Microvascular Abnormalities in Cerebrovascular Disease.

Cerebrovascular disease (CeVD) is one of the leading global causes of death and severe disability. To date, retinal microangiopathy has become a reflection of cerebral microangiopathy, mirroring the vascular pathological modifications in vivo. To evaluate the retinal structure and microvasculature in patients with CeVD, we conducted a cross-sectional study in Zhongshan Ophthalmic Center and Department of Neurology of Third Affiliated Hospital, Sun Yat-sen University using optical coherence tomography angiography (OCTA). CeVD patients (n = 121; 238 eyes) and healthy controls (n = 44; 57 eyes) were included in the analysis. The CeVD group showed significant thinning of the peripapillary retinal nerve fiber layer (pRNFL) thickness in the temporal and nasal quadrants, and thinning of the macular ganglion cell-inner plexiform layer (GC-IPL) in the inferior quadrant, while macular microvasculature reduction was prominent in all nine quadrants. There were significant correlations between OCTA parameters, visual acuity, and transcranial doppler parameters in the CeVD group. The specific structural parameters combining microvasculature indices showed the best diagnostic accuracies (AUC = 0.918) to discriminate CeVD group from healthy controls. To conclude, we proved that OCTA reveals specific patterns of retinal structural changes and extensive macular microvascular changes in CeVD. Additionally, these retinal abnormalities could prove useful disease biomarkers in the management of individuals at high risk of debilitating complications from a cerebrovascular event

Comparison of macular structural and vascular changes in neuromyelitis optica spectrum disorder and primary open angle glaucoma: a cross-sectional study.

AIMS: To compare macular structure and vasculature between neuromyelitis optica spectrum disorder (NMOSD) and primary open angle glaucoma (POAG) using optical coherence tomography angiography. METHODS: NMOSD patients (n=124) with/without a history of optic neuritis (ON) (NMO+ON: 113 eyes; NMO-ON: 95 eyes), glaucomatous patients (n=102) with early/advanced glaucoma (G-E: 74 eyes; G-A: 50 eyes) and healthy controls (n=62; 90 eyes) were imaged. The main outcome measures were macular ganglion cell-inner plexiform layer (GC-IPL) thickness, vessel density (VD) and perfusion density (PD) in the superficial capillary plexus, and diagnostic capabilities of the parameters as calculated by area under the curve (AUC). RESULTS: Significant losses in GC-IPL, VD and PD were detected in both patients with NMOSD and POAG. With matched losses in the peripapillary retinal nerve fibre layer, NMOSD group showed significant thinning of GC-IPL in the nasal-superior quadrant, whereas in POAG group, significant thinning was observed in the inferior and temporal-inferior quadrants. GC-IPL thinning was more prominent in the superior, nasal-superior and nasal-inferior quadrants in NMO+ON eyes. In G-A eyes, significant GC-IPL thinning was seen in the temporal-inferior quadrant. The specific structural parameters combining VD and foveal avascular zone (FAZ) indices showed the best diagnostic accuracies. The FAZ area in eyes with NMOSD was significantly smaller than the eyes of healthy controls and POAG. CONCLUSION: NMOSD and POAG have specific patterns of macular structural and vascular changes associated with pathophysiology. Our results indicate that FAZ could be a sensitive biomarker of macular changes in NMOSD

An improved method of searching inferior parathyroid gland for the patients with papillary thyroid carcinoma based on a retrospective study

ObjectiveMany surgeons knew the importance of parathyroid gland (PG) in the thyroid surgery, but it was even more difficult to be protected. This study aimed at evaluating the effectiveness of the improved method of searching inferior parathyroid gland (IPG).Methods213 patients were enrolled and divided into test and control groups according to different methods of searching IPG in the surgery. Consequently, we compared the surgical outcome parameters between the two groups, including the operative time, numbers of PG identifying (PG protection in situ, PG auto-transplantation, and PG accidental removal), numbers of the total lymph node (LN) and metastatic LN, parathyroid hormone (PTH), transient hypoparathyroidism, transient recurrent laryngeal nerve palsy, and postoperative bleeding.ResultsWe identified 194 (194/196, 98.98%) and 215 (215/230, 93.48%) PGs in the test group and control group, respectively, and there was a significant difference (P = 0.005), and this result was due to IPG identification differences (96/98, 97.96% vs. 100/115, 86.96%, P = 0.004). Meanwhile, there was a lower ratio of IPG auto-transplantation in the test group compared with that in the control group (46.94% vs. 64.35%, P = 0.013). Serum PTH one day after the operation was 3.65 ± 1.86 vs. 2.96 ± 1.64 (P = 0.043) but with no difference at 6 months. There were no differences in metastatic LN and recurrent laryngeal nerve palsy between two groups.ConclusionThe improved method of searching IPG was simple, efficient, and safe, which was easy to be implemented for searching IPG and protecting it well

Cold-induced modulation and functional analyses of the DRE-binding transcription factor gene, GmDREB3, in soybean (Glycine max L.)

DREB (dehydration-responsive element-binding protein) transcription factors have important roles in the stress-related regulation network in plants. A DREB orthologue, GmDREB3, belonging to the A-5 subgroup of the DREB subfamily, was isolated from soybean using the RACE (rapid amplification of cDNA ends) method. Northern blot analysis showed that expression of GmDREB3 in soybean seedlings was induced following cold stress treatment for 0.5 h and was not detected after 3 h. However, it was not induced by drought and high salt stresses or by abscisic acid (ABA) treatment. This response was similar to those of members in the A-1 subgroup and different from those of other members in the A-5 subgroup, suggesting that the GmDREB3 gene was involved in an ABA-independent cold stress-responsive signal pathway. Furthermore, analysis of the GmDREB3 promoter elucidated its cold-induced modulation. A promoter fragment containing bases −1058 to −664 was involved in response to cold stress, and its effect was detected for 1 h after treatment, but a transcriptional repressor appeared to impair this response by binding to a cis-element in the region −1403 to −1058 at 24 h after the beginning of cold stress. Moreover, the GmDREB3 protein could specifically bind to the DRE element in vitro, and activated expression of downstream reporter genes in yeast cells. In addition, overexpression of GmDREB3 enhanced tolerance to cold, drought, and high salt stresses in transgenic Arabidopsis. Physiological analyses indicated that the fresh weight and osmolality of GmDREB3 transgenic Arabidopsis under cold stress were higher than those of wild-type controls. GmDREB3 transgenic tobacco accumulated higher levels of free proline under drought stress and retained higher leaf chlorophyll levels under high salt stress than wild-type tobacco. In addition, constitutive expression of GmDREB3 in transgenic Arabidopsis caused growth retardation, whereas its expression under control of the stress-inducible Rd29A promoter minimized negative effects on plant growth under normal growth conditions, indicating that a combination of the Rd29A promoter and GmDREB3 might be useful for improving tolerance to environmental stresses in crop plants

Local Buckling Development of H-Section Steel Core of Buckling-Restrained Brace

To enhance the theoretical basis for the half-wavelength evaluation of high-order local buckling of section steel used as inner core of buckling-restrained brace, this paper conducts theoretical and numerical studies on the local buckling development of an H-section steel core of buckling restrained brace. Firstly, the elastic buckling development of the flange under monotonic compression is theoretically discussed based on the elastic buckling theory of plate and the principle of virtual displacement. The numerical model for the buckling restrained brace with H-section steel core is then established based on Abaqus, and the elastic buckling development of the flange is validated. Finally, further numerical studies are conducted to reveal the elasto-plastic buckling development of the flange and web under cyclic loading. It is found that the local buckling development of the flange and web of the H-section steel core are different from that of the flat plate core of buckling restrained brace. Under cyclic loading, the shortest buckling wave of the flange and web are induced by the buckling of plates on the two sides of the contact point near the ends. It is confirmed that there is no need to consider the lateral support from the restraining members to evaluate the minimum half-wavelength of high-order local buckling for section steel core of buckling-restrained brace

Generation of High-Amylose Rice through CRISPR/Cas9-Mediated Targeted Mutagenesis of Starch Branching Enzymes

Cereals high in amylose content (AC) and resistant starch (RS) offer potential health benefits. Previous studies using chemical mutagenesis or RNA interference have demonstrated that starch branching enzyme (SBE) plays a major role in determining the fine structure and physical properties of starch. However, it remains a challenge to control starch branching in commercial lines. Here, we use CRISPR/Cas9 technology to generate targeted mutagenesis in SBEI and SBEIIb in rice. The frequencies of obtained homozygous or bi-allelic mutant lines with indels in SBEI and SBEIIb in T0 generation were from 26.7 to 40%. Mutations in the homozygous T0 lines stably transmitted to the T1 generation and those in the bi-allelic lines segregated in a Mendelian fashion. Transgene-free plants carrying only the frame-shifted mutagenesis were recovered in T1 generation following segregation. Whereas no obvious differences were observed between the sbeI mutants and wild type, sbeII mutants showed higher proportion of long chains presented in debranched amylopectin, significantly increased AC and RS content to as higher as 25.0% and 9.8%, respectively, and thus altered fine structure and nutritional properties of starch. Taken together, our results demonstrated for the first time the feasibility to create high-amylose rice through CRISPR/Cas9-mediated editing of SBEIIb

Synthesis-dependent repair of Cpf1-induced double strand DNA breaks enables targeted gene replacement in rice.

The recently developed CRISPR (clustered regularly interspaced short palindromic repeats)/Cpf1 system expands the range of genome editing and is emerging as an alternative powerful tool for both plant functional genomics and crop improvement. Cpf1-CRISPR RNA (crRNA) produces double strand DNA breaks (DSBs) with long 5'-protruding ends, which may facilitate the pairing and insertion of repair templates through homology-directed repair (HDR) for targeted gene replacement and introduction of the desired DNA elements at specific gene loci for crop improvement. However, the potential mechanism underlying HDR of DSBs generated by Cpf1-crRNA remains to be investigated, and the inherent low efficiency of HDR and poor availability of exogenous donor DNA as repair templates strongly impede the use of HDR for precise genome editing in crop plants. Here, we provide evidence of synthesis-dependent repair of Cpf1-induced DSBs, which enables us precisely to replace the wild-type ALS gene with the intended mutant version that carries two discrete point mutations conferring herbicide resistance to rice plants. Our observation that the donor repair template (DRT) with only the left homologous arm is sufficient for precise targeted allele replacement offers a better understanding of the mechanism underlying HDR in plants, and greatly simplifies the design of DRTs for precision genome editing in crop improvement

Optical Coherence Tomography Angiography Reveals Distinct Retinal Structural and Microvascular Abnormalities in Cerebrovascular Disease.

Cerebrovascular disease (CeVD) is one of the leading global causes of death and severe disability. To date, retinal microangiopathy has become a reflection of cerebral microangiopathy, mirroring the vascular pathological modifications in vivo. To evaluate the retinal structure and microvasculature in patients with CeVD, we conducted a cross-sectional study in Zhongshan Ophthalmic Center and Department of Neurology of Third Affiliated Hospital, Sun Yat-sen University using optical coherence tomography angiography (OCTA). CeVD patients (n = 121; 238 eyes) and healthy controls (n = 44; 57 eyes) were included in the analysis. The CeVD group showed significant thinning of the peripapillary retinal nerve fiber layer (pRNFL) thickness in the temporal and nasal quadrants, and thinning of the macular ganglion cell-inner plexiform layer (GC-IPL) in the inferior quadrant, while macular microvasculature reduction was prominent in all nine quadrants. There were significant correlations between OCTA parameters, visual acuity, and transcranial doppler parameters in the CeVD group. The specific structural parameters combining microvasculature indices showed the best diagnostic accuracies (AUC = 0.918) to discriminate CeVD group from healthy controls. To conclude, we proved that OCTA reveals specific patterns of retinal structural changes and extensive macular microvascular changes in CeVD. Additionally, these retinal abnormalities could prove useful disease biomarkers in the management of individuals at high risk of debilitating complications from a cerebrovascular event

Unusual Presentation in WAGR Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Diseases

The deletion of chromosome 11p13 involving the WT1 and PAX6 genes has been shown to cause WAGR syndrome (OMIM #194072), a rare genetic disorder that features Wilms’ tumor, aniridia, genitourinary anomalies, as well as mental retardation. In this study, we expand the genotypic and phenotypic spectrum of WAGR syndrome by reporting on six patients from six unrelated families with different de novo deletions located on chromosome 11p13. Very rare phenotypes of lens automated absorption and lens thinning were detected in four of the six patients. We assessed the involvement of the ARL14EP gene in patients with and without severe lens abnormalities and found that its deletion may worsen the lens abnormalities in these patients