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Purpose: Knee osteoarthritis (KOA) is a common disorder among middle and older individuals. Electroacupuncture and exercise are present as two popular physical therapies for the management of KOA, and both were demonstrated to produce considerable results. However, the clinical decision-making process between these therapeutic interventions remains challenging due to the limited evidence of distinctions in their respective effects. This study aims to evaluate the clinical effect and cost effectiveness of electroacupuncture versus exercise in patients with KOA., Study Design and Methods: This is a randomized controlled trial in which 196 symptomatic KOA patients will be randomly assigned 1:1 either to the electroacupuncture group (n = 98) and the exercise group (n = 98). Patients in the electroacupuncture group will receive acupuncture with electric stimulation 3 times a week for 8 weeks, whereas patients in the exercise group will receive neuromuscular training twice a week for 8 weeks. Education concerning KOA management will be provided in both therapies. Co-primary outcomes include changes in numerical rating scale (NRS) and Knee injury and Osteoarthritis Outcome Score (KOOS) Activities of Daily Living (ADL) subscale from baseline at week 8. Secondary outcomes include KOOS Pain subscale, KOOS knee-related Quality of Life (QOL) subscale, Short Form 6 Dimensions (SF-6D), five-level EuroQol five-dimensional questionnaire (EQ-5D-5L), Credibility/ Expectancy Questionnaire, Patient's global assessment (PGA), 30-second Chair Stand Test (30s-CST), 40m (4*10m) Fast Paced Walk Test (40m FPWT), and Daily Physical Activity level (DPA)., Discussion: The results of this study will provide evidence regarding differences between these 2 physical therapies in multiple aspects and will provide specific guidance for the development of treatments based on the needs of individual patients., Trial Registration: ChiCTR2300070376., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To validate retinal capillary density and caliber associations with diabetic retinopathy (DR) severity in different clinical settings., Methods: This cross-sectional study assessed retinal capillary density and caliber in the superficial retinal layer of 3-mm OCTA scans centered on the fovea. Images were collected from non-diabetic controls and subjects with mild or referable DR (defined DR worse than mild DR) between February 2016 and December 2019 at secondary and tertiary eye care centers. Vessel Skeleton Density (VSD), a measure of capillary density, and Vessel Diameter Index (VDI), a measure of vascular caliber, were calculated from these images. Discriminatory performance of VSD and VDI was evaluated using multivariable logistic regression models predicting DR severity with adjustments for sex, hypertension, and hyperlipidemia. Area under the curve (AUC) was estimated. Model performance was evaluated in two different cohorts., Results: This study included 594 eyes from 385 subjects. Cohort 1 was a training cohort of 509 eyes including 159 control, 155 mild non-proliferative DR (NPDR) and 195 referable DR eyes. Cohort 2 was a validation cohort consisting of 85 eyes including 16 mild NPDR and 69 referable DR eyes. In Cohort 1, addition of VSD and VDI to a model using only demographic data significantly improved the model's AUC for discrimination of eyes with any DR severity from controls (0.91 [95% CI, 0.88-0.93] versus 0.80 [95% CI, 0.76-0.83], p < 0.001) and eyes with referable DR from mild NPDR (0.90 [95% CI, 0.86-0.93] versus 0.69 [95% CI, 0.64-0.75], p < 0.001). The transportability of this regression model was excellent when implemented in Cohort 2 for the referable DR versus mild NPDR comparison. The odds ratio of having any DR compared to control subjects, and referable DR compared to mild DR decreased by 15% (95% CI: 12-18%), and 13% (95% CI: 10-15%), respectively, for every 0.001 unit increase in VSD after adjusting for comorbidities., Conclusion: OCTA-derived capillary density has real world clinical value for rapidly assessing DR severity., Competing Interests: AHK - NIH Grants: R01EY030564, K08EY027006, Carl Zeiss Meditec (https://www.zeiss.com/meditec/us/about-us/contact-us.html) (Financial Support); RW - NIH Grant: R01EY028753, Carl Zeiss Meditec (https://www.zeiss.com/meditec/us/about-us/contact-us.html) (Financial Support); Carl Zeiss Meditec (Patents US8180134B2, US9013555B2, US9759544B2 and US10354378B2), Carl Zeiss Meditec (https://www.zeiss.com/meditec/us/about-us/contact-us.html) (Consultant), Kowa Inc (https://www.kowa-usa.com/about-us.html) (Patent). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To quantitatively assess choriocapillaris (CC) flow deficits in eyes with diabetic retinopathy (DR) using swept-source optical coherence tomography angiography (SS-OCTA)., Methods: Diabetic subjects with different stages of DR and age-matched healthy subjects were recruited and imaged with SS-OCTA. The en face CC blood flow images were generated using previously published and validated algorithms. The percentage of CC flow deficits (FD%) and the mean CC flow deficit size were calculated in a 5-mm-diameter circle centered on the fovea from the 6×6-mm scans., Results: Forty-five diabetic subjects and 27 control subjects were included in the study. The CC FD% in diabetic eyes was on average 1.4-fold greater than in control eyes (12.34±4.14% vs 8.82±2.61%, P < 0.001). The mean CC FD size in diabetic eyes was on average 1.4-fold larger than in control eyes (2151.3± 650.8μm2 vs 1574.4±255.0 μm2, P < 0.001). No significant difference in CC FD% or mean CC FD size was observed between eyes with nonproliferative DR and eyes with proliferative DR (P = 1.000 and P = 1.000, respectively)., Conclusions: CC perfusion in DR can be objectively and quantitatively assessed with FD% and FD size. In the macular region, both CC FD% and CC FD size are increased in eyes with DR. SS-OCTA provides new insights for the investigations of CC perfusion status in diabetes in vivo., Competing Interests: This work is supported in part by Carl Zeiss Meditec Inc, an industry partner. While all other authors do not have competing interests with Carl Zeiss, Dr Wang declare that he is a consultant with Carl Zeiss and holds a patent jointly with Carl Zeiss. However, this relationship does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To investigate the relationships between global and sectoral macular vascular microcirculation parameters in the ganglion cell-inner plexiform layer (GCIPL) assessed by optical coherence tomography angiography (OCTA), and global and sectoral visual field (VF) central mean sensitivity (CMS) assessed by standard automated perimetry., Methods: Fifty-four eyes with open angle glaucoma were scanned using a swept-source OCTA (Plex Elite 9000, Zeiss, Dublin, CA) and macular vascular microcirculation was measured by calculating the overall flux and vessel area density (VAD) over the entire 6mm x 6mm area, excluding large retinal vessels. Central 10-degree VF CMS was calculated based on 24-2 VF. Pearson correlation was used to investigate the correlation between global and sectoral OCTA parameters and global and sectoral VF CMS., Results: Both global GCIPL flux and VAD were significantly correlated with VF CMS (p<0.001). For the sectoral analysis, sectoral VAD was significantly correlated with sectoral VF CMS in all comparisons except for the inferonasal VF CMS with supero-temporal (ST) GCIPL VAD (p = 0.097). Although highest correlation was observed for both ST VF CMS with inferior GCIPL VAD and infero-temporal VF CMS with superior GCIPL VAD (r = 0.683, p<0.001), there was no significant difference in correlation when compared to the global VAD and other sectors' correlation coefficients (p≥ 0.091), except for the ST GCIPL VAD (p = 0.001)., Conclusions: Global and sectoral macular vascular microcirculation in the GCIPL, as determined by OCTA, was significantly correlated with global and sectoral VF CMS in glaucomatous patients. OCTA can aid in the understanding of the structure-function relationships of the macular region., Competing Interests: The authors have made the following financial disclosures: Dr. Wang receives royalties from intellectual property owned by Oregon Health & Science University and research support from Carl Zeiss Meditec Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To quantitatively evaluate the retinal microvasculature in human subjects with retinal venous occlusions (RVO) using optical coherence tomography angiography (OCTA)., Design: Retrospective, cross-sectional, observational case series., Participants: Sixty subjects (84 eyes) were included (20 BRVO, 14 CRVO, 24 unaffected fellow eyes, and 26 controls)., Methods: OCTA was performed on a prototype, spectral domain-OCTA system in the 3x3mm central macular region. Custom software was used to quantify morphology and density of retinal capillaries using four quantitative parameters. The vasculature of the segmented retinal layers and nonsegmented whole retina were analyzed., Main Outcome Measures: Fractal dimension (FD), vessel density (VD), skeletal density (SD), and vessel diameter index (VDI) within the segmented retinal layers and nonsegmented whole retina vasculature., Results: Nonsegmented analysis of RVO eyes demonstrated significantly lower FD (1.64±0.01 vs 1.715±0.002; p<0.001), VD (0.32±0.01 vs 0.432±0.002; p<0.001), and SD (0.073±0.004 vs 0.099±0.001; p<0.001) compared to controls. Compared to the fellow eye, FD, VD and SD were lower (p<0.001), and VDI was higher (p<0.001). FD, VD, and SD progressively decreased as the extent (or type) of RVO increased (control vs BRVO vs CRVO; p<0.001). In the unaffected fellow eye FD, VD and SD showed significant differences when compared to control eyes or affected RVO eyes (p<0.001)., Conclusions: Quantitative OCTA of the central 3x3mm macular region demonstrates significant differences in capillary density and morphology among subjects with BRVO and CRVO compared to controls or unaffected fellow eyes in all vascular layers. The unaffected fellow eyes also demonstrate significant differences when compared to controls. OCTA allows for noninvasive, layer-specific, quantitative evaluation of RVO-associated microvascular changes.

We report the use of a high-resolution optical coherence tomography (OCT) imaging platform to identify and quantify pressure-dependent aqueous outflow system (AOS) tissue relationships and to infer mechanical stiffness through examination of tissue properties in ex vivo human eyes. Five enucleated human eyes are included in this study, with each eye prepared with four equal-sized quadrants, each encompassing 90 degrees of the limbal circumference. In radial limbal segments perfusion pressure within Schlemm's canal (SC) is controlled by means of a perfusion cannula inserted into the canal lumen, while the other end of the cannula leads to a reservoir at a height that can control the pressure in the cannula. The OCT system images the sample with a spatial resolution of about 5 μm from the trabecular meshwork (TM) surface. Geometric parameters are quantified from the 2D OCT images acquired from the sample subjected to controlled changes in perfusion pressures; parameters include area and height of the lumen of SC, collector channel entrances (CCE) and intrascleral collector channels (ISCC). We show that 3D OCT imaging permits the identification of 3-D relationships of the SC, CCE and ISCC lumen dimensions. Collagen flaps or leaflets are found at CCE that are attached or hinged at only one end, whilst the flaps are connected to the TM by cylindrical structures spanning SC. Increasing static SC pressures resulted in SC lumen enlargement with corresponding enlargement of the CCE and ISCC lumen. Pressure-dependent SC lumen area and height changes are significant at the 0.01 levels for ANOVA, and at the 0.05 for both polynomial curves and Tukey paired comparisons. Dynamic measurements demonstrate a synchronous increase in SC, CCE and ISCC lumen height in response to pressure changes from 0 to 10, 30 or 50 mm Hg, respectively, and the response time is within the 50-millisecond range. From the measured SC volume and corresponding IOP values, we demonstrate that an elastance curve can be developed to infer the mechanical stiffness of the TM by means of quantifying pressure-dependent SC volume changes over a 2 mm radial region of SC. Our study finds pressure-dependent motion of the TM that corresponds to collagen leaflet configuration motion at CCE; the synchronous tissue motion also corresponds with synchrony of SC and CCE lumen dimension changes., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To investigate optic disc perfusion differences in normal, primary open-angle glaucoma (POAG), and normal tension glaucoma (NTG) eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique., Design: Cross-sectional, observational study., Subjects: Twenty-eight normal, 30 POAG, and 31 NTG subjects., Methods: One eye from each subject was scanned with a 68 kHz Cirrus HD-OCT 5,000-based OMAG prototype system centered at the optic nerve head (ONH) (Carl Zeiss Meditec Inc, Dublin, CA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program., Main Outcome Measures: Optic disc perfusion, quantified as flux, vessel area density, and normalized flux (flux normalized by the vessel area) within the ONH., Results: Glaucomatous eyes had significantly lower optic disc perfusion in preLC in all three perfusion metrics (p<0.0001) compared to normal eyes. The visual field (VF) mean deviation (MD) and pattern standard deviation (PSD) were similar between the POAG and NTG groups, and no differences in optic disc perfusion were observed between POAG and NTG. Univariate analysis revealed significant correlation between optic disc perfusion and VF MD, VF PSD, and rim area in both POAG and NTG groups (p≤0.0288). However, normalized optic disc perfusion was correlated with some structural measures (retinal nerve fiber layer thickness and ONH cup/disc ratio) only in POAG eyes., Conclusions: Optic disc perfusion detected with OMAG was significantly reduced in POAG and NTG groups compared to normal controls, but no difference was seen between POAG and NTG groups with similar levels of VF damage. Disc perfusion was significantly correlated with VF MD, VF PSD, and rim area in glaucomatous eyes. Vascular changes at the optic disc as measured using OMAG may provide useful information for diagnosis and monitoring of glaucoma.

Genetic maps are important tools in plant genomics and breeding. The present study reports the large-scale discovery of single nucleotide polymorphisms (SNPs) for genetic map construction in tea plant. We developed a total of 6,042 valid SNP markers using specific-locus amplified fragment sequencing (SLAF-seq), and subsequently mapped them into the previous framework map. The final map contained 6,448 molecular markers, distributing on fifteen linkage groups corresponding to the number of tea plant chromosomes. The total map length was 3,965 cM, with an average inter-locus distance of 1.0 cM. This map is the first SNP-based reference map of tea plant, as well as the most saturated one developed to date. The SNP markers and map resources generated in this study provide a wealth of genetic information that can serve as a foundation for downstream genetic analyses, such as the fine mapping of quantitative trait loci (QTL), map-based cloning, marker-assisted selection, and anchoring of scaffolds to facilitate the process of whole genome sequencing projects for tea plant.

In vivo imaging of mouse brain vasculature typically requires applying skull window opening techniques: open-skull cranial window or thinned-skull cranial window. We report non-invasive 3D in vivo cerebral blood flow imaging of C57/BL mouse by the use of ultra-high sensitive optical microangiography (UHS-OMAG) and Doppler optical microangiography (DOMAG) techniques to evaluate two cranial window types based on their procedures and ability to visualize surface pial vessel dynamics. Application of the thinned-skull technique is found to be effective in achieving high quality images for pial vessels for short-term imaging, and has advantages over the open-skull technique in available imaging area, surgical efficiency, and cerebral environment preservation. In summary, thinned-skull cranial window serves as a promising tool in studying hemodynamics in pial microvasculature using OMAG or other OCT blood flow imaging modalities.

The MYB proteins comprise one of the largest families of transcription factors (TFs) in plants. Although several MYB genes have been characterized to play roles in secondary metabolism, the MYB family has not yet been identified in apple. In this study, 229 apple MYB genes were identified through a genome-wide analysis and divided into 45 subgroups. A computational analysis was conducted using the apple genomic database to yield a complete overview of the MYB family, including the intron-exon organizations, the sequence features of the MYB DNA-binding domains, the carboxy-terminal motifs, and the chromosomal locations. Subsequently, the expression of 18 MYB genes, including 12 were chosen from stress-related subgroups, while another 6 ones from other subgroups, in response to various abiotic stresses was examined. It was found that several of these MYB genes, particularly MdoMYB121, were induced by multiple stresses. The MdoMYB121 was then further functionally characterized. Its predicted protein was found to be localized in the nucleus. A transgenic analysis indicated that the overexpression of the MdoMYB121 gene remarkably enhanced the tolerance to high salinity, drought, and cold stresses in transgenic tomato and apple plants. Our results indicate that the MYB genes are highly conserved in plant species and that MdoMYB121 can be used as a target gene in genetic engineering approaches to improve the tolerance of plants to multiple abiotic stresses.

Optical microangiography (OMAG) and Doppler optical microangiography (DOMAG) are two non-invasive techniques capable of determining the tissue microstructural content, microvasculature angiography, and blood flow velocity and direction. These techniques were used to visualize the acute and chronic microvascular and tissue responses upon an injury in vivo. A tissue wound was induced using a 0.5 mm biopsy punch on a mouse pinna. The changes in the microangiography, blood flow velocity and direction were quantified for the acute (<30 min) wound response and the changes in the tissue structure and microangiography were determined for the chronic wound response (30 min-60 days). The initial wound triggered recruitment of peripheral capillaries, as well as redirection of main arterial and venous blood flow within 3 min. The complex vascular networks and new vessel formation were quantified during the chronic response using fractal dimension. The highest rate of wound closure occurred between days 8 and 22. The vessel tortuosity increased during this time suggesting angiogenesis. Taken together, these data signify that OMAG has the capability to track acute and chronic changes in blood flow, microangiography and structure during wound healing. The use of OMAG has great potential to improve our understanding of vascular and tissue responses to injury in order to develop more effective therapeutics.

A synchronized dual-wavelength laser speckle contrast imaging (DWLSCI) system and a Doppler optical microangiography (DOMAG) system was developed to determine several ischemic parameters in the cochlea due to a systemic hypoxic challenge. DWLSCI can obtain two-dimensional data, and was used to determine the relative changes in cochlear blood flow, and change in the concentrations of oxyhemoglobin (HbO), deoxyhemoglobin (Hb) and total hemoglobin (HbT) in mice. DOMAG can obtain three-dimensional data, and was used to determine the changes in cochlear blood flow with single vessel resolution. It was demonstrated that during a hypoxic challenge there was an increase in the concentrations of Hb, a decrease in the concentrations of HbO and cochlear blood flow, and a slight decrease in the concentration of HbT. Also, the rate of change in the concentrations of Hb and HbO was quantified during and after the hypoxic challenge. The ability to simultaneously measure these ischemic parameters with high spatio-temporal resolution will allow the detailed quantitative analysis of several hearing disorders, and will be useful for diagnosing and developing treatments.

Background: Mammalian hearing is refined by amplification of the sound-evoked vibration of the cochlear partition. This amplification is at least partly due to forces produced by protein motors residing in the cylindrical body of the outer hair cell. To transmit power to the cochlear partition, it is required that the outer hair cells dynamically change their length, in addition to generating force. These length changes, which have not previously been measured in vivo, must be correctly timed with the acoustic stimulus to produce amplification., Methodology/principal Findings: Using in vivo optical coherence tomography, we demonstrate that outer hair cells in living guinea pigs have length changes with unexpected timing and magnitudes that depend on the stimulus level in the sensitive cochlea., Conclusions/significance: The level-dependent length change is a necessary condition for directly validating that power is expended by the active process presumed to underlie normal hearing.

Oxygen availability is regarded as a critical factor to metabolically regulate systemic blood flow. There is a debate as to how peripheral blood flow (PBF) is affected and modulated during hypoxia and hyperoxia; however in vivo evaluating of functional PBF under oxygen-related physiological perturbation remains challenging. Microscopic observation, the current frequently used imaging modality for PBF characterization often involves the use of exogenous contrast agents, which would inevitably perturb the intrinsic physiologic responses of microcirculation being investigated. In this paper, optical micro-angiography (OMAG) was employed that uses intrinsic optical scattering signals backscattered from blood flows for imaging PBF in skeletal muscle challenged by the alteration of oxygen concentration. By utilizing optical reflectance signals, we demonstrated that OMAG is able to show the response of hemodynamic activities upon acute hypoxia and hyperoxia, including the modulation of macrovascular caliber, microvascular density, and flux regulation within different sized vessels within skeletal muscle in mice in vivo. Our results suggest that OMAG is a promising tool for in vivo monitoring of functional macro- or micro-vascular responses within peripheral vascular beds.