PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.

BACKGROUND: Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness of SMCs is a major determinant of total arterial stiffness. We hypothesized that PAI-1 promotes SMC stiffness by regulating the cytoskeleton and that pharmacological inhibition of PAI-1 decreases SMC and aortic stiffness. METHODS: PAI-039, a specific inhibitor of PAI-1, and small interfering RNA were used to inhibit PAI-1 expression in cultured human SMCs. Effects of PAI-1 inhibition on SMC stiffness, F-actin (filamentous actin) content, and cytoskeleton-modulating enzymes were assessed. WT (wild-type) and PAI-1-deficient murine SMCs were used to determine PAI-039 specificity. RNA sequencing was performed to determine the effects of PAI-039 on SMC gene expression. In vivo effects of PAI-039 were assessed by aortic pulse wave velocity. RESULTS: PAI-039 significantly reduced intrinsic stiffness of human SMCs, which was accompanied by a significant decrease in cytoplasmic F-actin content. PAI-1 gene knockdown also decreased cytoplasmic F-actin. PAI-1 inhibition significantly increased the activity of cofilin, an F-actin depolymerase, in WT murine SMCs, but not in PAI-1-deficient SMCs. RNA-sequencing analysis suggested that PAI-039 upregulates AMPK (AMP-activated protein kinase) signaling in SMCs, which was confirmed by Western blotting. Inhibition of AMPK prevented activation of cofilin by PAI-039. In mice, PAI-039 significantly decreased aortic stiffness and tunica media F-actin content without altering the elastin or collagen content. CONCLUSIONS: PAI-039 decreases intrinsic SMC stiffness and cytoplasmic stress fiber content. These effects are mediated by AMPK-dependent activation of cofilin. PAI-039 also decreases aortic stiffness in vivo. These findings suggest that PAI-1 is an important regulator of the SMC cytoskeleton and that pharmacological inhibition of PAI-1 has the potential to prevent and treat cardiovascular diseases involving arterial stiffening.

Event-triggered background-oriented schlieren: high-frequency visualization of a heated jet flow.

This Letter reports a novel, to our knowledge, event-triggered background-oriented schlieren (EBOS) technique using a combination of an event-triggered camera and pulsed laser speckle projection. The BOS images are reconstructed using the event data generated by the pulsed laser speckle projection and then processed to obtain the density and temperature distribution of the flow. This technique enables continuous visualization and recording of flows at kFPS frame rates with a very low cost, breaking through the short operating times of existing high-frame-rate BOSs. To examine the event-triggered BOS technique, tests are conducted on a hot air gun. The measured temperature distribution coincides with the thermocouple data with an error of no more than 10.8%. Measurements taken during the start-up of the hot air gun demonstrate that the presented technique can measure the evolution of the jet temperature for at least 150 s, as well as capture the localized unsteady turbulent structure in the heated jet flow.

The impact of multifactorial stress combination on reproductive tissues and grain yield of a crop plant.

Global warming, climate change, and industrial pollution are altering our environment subjecting plants, microbiomes, and ecosystems to an increasing number and complexity of abiotic stress conditions, concurrently or sequentially. These conditions, termed, "multifactorial stress combination" (MFSC), can cause a significant decline in plant growth and survival. However, the impacts of MFSC on reproductive tissues and yield of major crop plants are largely unknown. We subjected soybean (Glycine max) plants to a MFSC of up to five different stresses (water deficit, salinity, low phosphate, acidity, and cadmium), in an increasing level of complexity, and conducted integrative transcriptomic-phenotypic analysis of their reproductive and vegetative tissues. We reveal that MFSC has a negative cumulative effect on soybean yield, that each set of MFSC condition elicits a unique transcriptomic response (that is different between flowers and leaves), and that selected genes expressed in leaves or flowers of soybean are linked to the effects of MFSC on different vegetative, physiological, and/or reproductive parameters. Our study identified networks and pathways associated with reactive oxygen species, ascorbic acid and aldarate, and iron/copper signaling/metabolism as promising targets for future biotechnological efforts to augment the resilience of reproductive tissues of major crop plants to MFSC. In addition, we provide unique phenotypic and transcriptomic datasets for dissecting the mechanistic effects of MFSC on the vegetative, physiological, and reproductive processes of a crop plant.

High-Density CuInS2 Quantum Dots for Efficient and Stable CO2 Electroreduction.

Electrochemically converting CO2 back into fuels and chemicals is promising in alleviating the greenhouse effect worldwide. Various high-efficiency catalysts have been achieved, yet the unsatisfied structural stability under CO2 electrolysis conditions restricts their practical application. Herein, a sub-5 nm sized CuInS2 quantum dots (CIS-QDs) based electrocatalyst for converting CO2 into CO are developed. Taking advantage of the stable M─Ch (metal-chalcogenide) covalent bonds, and unique p-block metal properties, the as-prepared catalyst exhibits excellent structural stability under large overpotentials and can achieve a high CO Faradaic efficiency (FE) of 86% (total CO2 reduction FE of 89%) at -0.65 V versus reversible hydrogen electrode with long-term durability of 40 h and outstanding current densities of 10.6 mA cm-2 simultaneously. Furthermore, detailed electrochemical analyses revealed that the excellent performance of the as-prepared catalysts shall be attributed to the high-density active sites and fast charge transfer brought by the ultrasmall size of CIS-QDs. This work provides insights into the design of high-density and stable catalytic sites for developing high-performance electrocatalysts.

The effects of multifactorial stress combination on rice and maize.

The complexity of environmental factors affecting crops in the field is gradually increasing due to climate change-associated weather events, such as droughts or floods combined with heat waves, coupled with the accumulation of different environmental and agricultural pollutants. The impact of multiple stress conditions on plants was recently termed "multifactorial stress combination" (MFSC) and defined as the occurrence of 3 or more stressors that impact plants simultaneously or sequentially. We recently reported that with the increased number and complexity of different MFSC stressors, the growth and survival of Arabidopsis (Arabidopsis thaliana) seedlings declines, even if the level of each individual stress is low enough to have no significant effect on plants. However, whether MFSC would impact commercial crop cultivars is largely unknown. Here, we reveal that a MFSC of 5 different low-level abiotic stresses (salinity, heat, the herbicide paraquat, phosphorus deficiency, and the heavy metal cadmium), applied in an increasing level of complexity, has a significant negative impact on the growth and biomass of a commercial rice (Oryza sativa) cultivar and a maize (Zea mays) hybrid. Proteomics, element content, and mixOmics analyses of MFSC in rice identified proteins that correlate with the impact of MFSC on rice seedlings, and analysis of 42 different rice genotypes subjected to MFSC revealed substantial genetic variability in responses to this unique state of stress combination. Taken together, our findings reveal that the impacts of MFSC on 2 different crop species are severe and that MFSC may substantially affect agricultural productivity.

Multi-Omics Analysis of Circulating Exosomes in Adherent Long-Term Treated OSA Patients.

Obstructive sleep apnea (OSA) is a highly prevalent chronic disease affecting nearly a billion people globally and increasing the risk of multi-organ morbidity and overall mortality. However, the mechanisms underlying such adverse outcomes remain incompletely delineated. Extracellular vesicles (exosomes) are secreted by most cells, are involved in both proximal and long-distance intercellular communication, and contribute toward homeostasis under physiological conditions. A multi-omics integrative assessment of plasma-derived exosomes from adult OSA patients prior to and after 1-year adherent CPAP treatment is lacking. We conducted multi-omic integrative assessments of plasma-derived exosomes from adult OSA patients prior to and following 1-year adherent CPAP treatment to identify potential specific disease candidates. Fasting morning plasma exosomes isolated from 12 adult patients with polysomnographically-diagnosed OSA were analyzed before and after 12 months of adherent CPAP therapy (mean ≥ 6 h/night) (OSAT). Exosomes were characterized by flow cytometry, transmission electron microscopy, and nanoparticle tracking analysis. Endothelial cell barrier integrity, wound healing, and tube formation were also performed. Multi-omics analysis for exosome cargos was integrated. Exosomes derived from OSAT improved endothelial permeability and dysfunction as well as significant improvement in tube formation compared with OSA. Multi-omic approaches for OSA circulating exosomes included lipidomic, proteomic, and small RNA (miRNAs) assessments. We found 30 differentially expressed proteins (DEPs), 72 lipids (DELs), and 13 miRNAs (DEMs). We found that the cholesterol metabolism (has04979) pathway is associated with lipid classes in OSA patients. Among the 12 subjects of OSA and OSAT, seven subjects had complete comprehensive exosome cargo information including lipids, proteins, and miRNAs. Multi-omic approaches identify potential signature biomarkers in plasma exosomes that are responsive to adherent OSA treatment. These differentially expressed molecules may also play a mechanistic role in OSA-induced morbidities and their reversibility. Our data suggest that a multi-omic integrative approach might be useful in understanding how exosomes function, their origin, and their potential clinical relevance, all of which merit future exploration in the context of relevant phenotypic variance. Developing an integrated molecular classification should lead to improved diagnostic classification, risk stratification, and patient management of OSA by assigning molecular disease-specific therapies.

[Oral panorama reconstruction method based on pre-segmentation and Bezier function].

For patients with partial jaw defects, cysts and dental implants, doctors need to take panoramic X-ray films or manually draw dental arch lines to generate Panorama images in order to observe their complete dentition information during oral diagnosis. In order to solve the problems of additional burden for patients to take panoramic X-ray films and time-consuming issue for doctors to manually segment dental arch lines, this paper proposes an automatic panorama reconstruction method based on cone beam computerized tomography (CBCT). The V-network (VNet) is used to pre-segment the teeth and the background to generate the corresponding binary image, and then the Bezier curve is used to define the best dental arch curve to generate the oral panorama. In addition, this research also addressed the issues of mistakenly recognizing the teeth and jaws as dental arches, incomplete coverage of the dental arch area by the generated dental arch lines, and low robustness, providing intelligent methods for dental diagnosis and improve the work efficiency of doctors.

Hip subluxation in children with spinal cord injury: Incidence and influencing factors.

OBJECTIVE: Hip subluxation is a common complication in children with spinal cord injury. This study aimed to investigate the incidence and influencing factors of hip subluxation and discuss prevention strategies. METHODS: Medical records of children with spinal cord injury were reviewed. The inclusion criteria were as follows: (1) the patient was younger than 18 years old when injured; (2) absence of traumatic or congenital pathological changes of the hip at the time of injury. The migration percentage and acetabular index were selected to evaluate hip stability and acetabulum development. Influencing factors of sex, age, injury duration, severity, level, and spasticity were analyzed. RESULTS: A total of 146 children were enrolled. Twenty-eight children presented with hip subluxation and were significantly younger at the time of injury than those with normal hips (P = 0.002). The incidence of hip subluxation increased with the prolonged injury duration. Injury before age 6, complete injury, and flaccid lower extremities were significant influencing factors (P = 0.003, 0.004, and 0.015, respectively). The risk of hip subluxation decreased by 18% for every year older in injury age (P = 0.031) and decreased by 85% in children with spasticity (P = 0.018) than those without. However, the risk of hip subluxation in children with injury duration longer than 1 year was 7.1 times higher than those with shorter injury duration (P < 0.001). CONCLUSIONS: The incidence of hip subluxation in children with spinal cord injury increased with the injury duration. Younger children had immature hip development. Due to complete injury and flaccid muscle, lack of protection around the hip may lead to subluxation. Follow-up and prevention of hip subluxation need the joint effort of medical staff and families.

Unconventional Bilateral Compressive Strained Ni-Ir Interface Synergistically Accelerates Alkaline Hydrogen Oxidation.

The alkaline hydrogen oxidation reaction (HOR) involves the coupling of adsorbed hydrogen (Had) and hydroxyl (OHad) species and is thus orders of magnitude slower than that in acid media. According to the Sabatier principle, developing electrocatalysts with appropriate binding energy for both intermediates is vital to accelerating the HOR though it is still challenging. Herein, we propose an unconventional bilateral compressive strained Ni-Ir interface (Ni-Ir(BCS)) as efficient synergistic HOR sites. Density functional theory (DFT) simulations reveal that the bilateral compressive strain effect leads to the appropriate adsorption for both Had and OHad, enabling their coupling thermodynamically spontaneous and kinetically preferential. Such Ni-Ir(BCS) is experimentally achieved by embedding sub-nanometer Ir clusters in graphene-loaded high-density Ni nanocrystals (Ni-Ir(BCS)/G). As predicted, it exhibits a HOR mass activity of 7.95 and 2.88 times those of commercial Ir/C and Pt/C together with much enhanced CO tolerance, respectively, ranking among the most active state-of-the-art HOR catalysts. These results provide new insights into the rational design of advanced electrocatalysts involving coordinated adsorption and activation of multiple reactants.

[Methylselenocysteine Promotes Etoposide Cytotoxicity by Enhancing Homotypic Gap Junctions Composed of Connexin 26].

Objective: To investigate the effect of methylselenocysteine (MSC) on the function of homotypic gap junction (GJ) composed of connexin (Cx) 26 and its regulation of chemotherapeutic drug cytotoxicity. Methods: The Tet-on HeLa cells transfected with and stably expressing Cx26 were used as the tool cells. Effects of MSC on cell growth, GJ function, and Cx26 protein expression were examined by MTT method, parachute assay, and Western blot analysis, respectively. The cytotoxicity of chemotherapeutic drugs was determined by standard colony-forming assay, and the relationship between MSC's effect on cytotoxicity of these chemotherapeutic drugs and its regulation of GJ was further analyzed. Results: In Tet-on HeLa cells, doxycycline (Dox) can induce the expression of Cx26, which could then form functional GJs. Within a concentration range of 50 µmol/L, MSC had no significant effect on HeLa cell growth. Non-toxic concentrations of MSC can enhance GJs in a concentration-dependent manner and exert its effect at the nanomolar level. This effect was associated with an induction of Cx26 protein expression by MSC. Among the three common chemotherapeutic agents with different mechanisms of action, etoposide (Eto) presented cytotoxicity differences between HeLa cells cultured at low density (nonconfluent, no GJ formed) and high density (confluent, GJ formed). What's more, the inhibitory effect of Eto combined with MSC on HeLa cell colony formation was stronger than that of Eto alone, and this effect occurred only in HeLa cells with GJ formation. Conclusion: MSC can potentiate the cytotoxicity of Eto by enhancing the GJs composed of Cx26, indicating that combined strategy of selenide and chemotherapy shows potential value in the treatment of malignant tumors.

Novel Physical Examination Tests for the Diagnosis of Chronic Sacroiliac Joint Dysfunction and Differentiate It From Lumbar Disc Herniation.

BACKGROUND: Traditional sacroiliac joint (SIJ) provocation tests have been used to diagnose SIJ pain. However, this can simply be changed to chronic SIJ dysfunction (cSIJD) manifests as mechanical changes in the pelvis and lower extremities in addition to pain. A novel composite of physical examinations based on the iliac pronation, pubic tubercle tenderness, and plantar fascia tenderness tests (IPP triple tests) was designed for the diagnosis of cSIJD. OBJECTIVES: To evaluate IPP triple tests in the diagnosis of cSIJD and differential diagnosis from lumbar disc herniation (LDH) in comparison with traditional provocation tests. STUDY DESIGN: Prospective single-blind controlled study. SETTING: This study was conducted at the Department of Spine and Spinal Cord Surgery of China Rehabilitation Research Center in Beijing, China. METHODS: One hundred and sixty-six patients were assigned into the cSIJD group, LDH group, or healthy control group. The cSIJD diagnosis was confirmed by SIJ injection. The diagnosis of LDH was confirmed according to the 2014 North American Spine Association diagnosis and treatment guidelines for LDH. All patients were examined with IPP triple tests and traditional provocation tests. The sensitivity, specificity, positive and negative likelihood ratios, and areas under the curve (AUCs) were used to evaluate the diagnostic accuracy of the composites or single of the IPP triple tests, and traditional provocation tests. The Delong's test was used for the comparison among AUCs. The kappa analysis was used for the IPP triple tests and traditional provocation tests compared with the reference standard (REF). The independent t test and chi-square test were used to analyze the influence factors (i.e., age, gender), and group on diagnostic accuracy. RESULTS: There was no statistical difference in gender (chi-squared = 0.282, P = 0.596) and age (F = 0.096, P = 0.757) between the 3 groups. The AUC of the iliac pronation test was 0.903 when it was used alone; the AUC of the novel composites of the IPP triple tests was 0.868 (95% confidence interval [CI] = 0.802-0.919); and the diagnostic accuracy of the traditional provocation test was relatively low (AUC = 0.597, 95% CI = 0.512-0.678). The diagnostic accuracy of the IPP triple tests was higher than that of the traditional provocation test, P < 0.05. Kappa consistency comparison showed that the kappa value between the IPP triple tests and the REF was 0.229, the kappa between the traditional provocation test and the REF was 0.052. The age of the patients with inaccurate diagnosis was higher than that of the patients with accurate diagnosis in both methods (traditional tests, P = 0.599; IPP:P = 0.553). Different types of diseases (groups) affect the accuracy of diagnosis, the proportion of inaccuracy of traditional provocation tests was higher than that of the IPP triple tests (77.8% vs 23.6%) in cSIJD, while the 2 methods have high differential diagnostic accuracy in LDH (96.77%) and control groups (97.56%). LIMITATIONS: Small size of LDH patients and differences in physical tests among examiners. CONCLUSIONS: The novel composites of IPP triple tests have higher accuracy than the traditional provocation tests in diagnosing cSIJD and both have good accuracy in differentiating cSIJD from LDH. IPP triple tests may be an alternative physical examination for clinical screening of cSIJD.

Spatio-Temporal Contextual Learning for Single Object Tracking on Point Clouds.

Single object tracking (SOT) is one of the most active research directions in the field of computer vision. Compared with the 2-D image-based SOT which has already been well-studied, SOT on 3-D point clouds is a relatively emerging research field. In this article, a novel approach, namely, the contextual-aware tracker (CAT), is investigated to achieve a superior 3-D SOT through spatially and temporally contextual learning from the LiDAR sequence. More precisely, in contrast to the previous 3-D SOT methods merely exploiting point clouds in the target bounding box as the template, CAT generates templates by adaptively including the surroundings outside the target box to use available ambient cues. This template generation strategy is more effective and rational than the previous area-fixed one, especially when the object has only a small number of points. Moreover, it is deduced that LiDAR point clouds in 3-D scenes are often incomplete and significantly vary from frame to another, which makes the learning process more difficult. To this end, a novel cross-frame aggregation (CFA) module is proposed to enhance the feature representation of the template by aggregating the features from a historical reference frame. Leveraging such schemes enables CAT to achieve a robust performance, even in the case of extremely sparse point clouds. The experiments confirm that the proposed CAT outperforms the state-of-the-art methods on both the KITTI and NuScenes benchmarks, achieving 3.9% and 5.6% improvements in terms of precision.

Prognosis of traumatic spinal cord injury in children: Follow-up of 86 patients.

PURPOSE: The long-term situation of children with spinal cord injury (SCI) was investigated, and suggestions for helping them better return to the society were provided. METHODS: SCI patients less than 18 years old hospitalized in Beijing Boai Hospital from January 2011 to December 2020 were retrospectively analyzed. Information including motor function, complications, characteristic changes, self-care abilities, school attendance and social participation were collected by telephone interview and electronic questionnaire. All the answers were statistically analyzed. RESULTS: A total of 86 cases were enrolled, 77 girls and 9 boys, with a median injury age of 6 years and 2 months. The follow-up time was 3-130 months. The main cause of trauma in these children was sport injury (66.3%), the thoracic spinal cord was involved the most (91.9%), and complete SCIs accounted for the majority (76.7%). In terms of complications, children with complete SCIs were more likely to have urinary incontinence, constipation and characteristic changes (p < 0.05); whereas the incomplete SCIs often have spasticity (p < 0.05). As to the daily living abilities, children with incomplete lumbar SCIs were more capable to accomplish personal hygiene, transfer, and bathing independently than those with complete injuries, or cervical/thoracic SCIs, respectively (p < 0.05). Moreover, children older than 9 years care more able to dress and transfer independently than the youngers (p < 0.05). Wheelchair users accounted for 84.9% and more than half of them were able to propel wheelchair independently, and those who move passively in wheelchairs were mostly introverted kids (p < 0.05). Almost all (93.8%) children with incomplete injuries were able to walk independently. Most (79.1%) children continued to attending school, and 41.9% participated in interest classes. Unfortunately, 67.4% of the children spent less time playing with their peers than before the injury. CONCLUSION: SCIs impair physical structures and function of children, affect their independence in daily living, and restrict school attendance and social interaction. Comprehensive rehabilitation after injury is a systematic work. Medical staff and caregivers should not only pay attention to neurological function, but also help them improve self-care abilities. It is also important to balance rehabilitation training and school work and social participation.

Sprouty4 is epigenetically upregulated in human colorectal cancer.

Sprouty4 (SPRY4) has been frequently reported as a tumor suppressor and is therefore downregulated in various cancers. For the first time, we report that SPRY4 is epigenetically upregulated in colorectal cancer (CRC). In this study, we explored DNA methylation and hydroxymethylation levels of SPRY4 in CRC cells and patient samples and correlated these findings with mRNA and protein expression levels. Three loci within the promoter region of SPRY4 were evaluated for 5mC levels in CRC using the combined bisulfite restriction analysis. In addition, hydroxymethylation levels within SPRY4 were measured in CRC patients. Lastly, DNA methylation and mRNA expression data were extracted from CRC patients in multiple high-throughput data repositories like Gene Expression Omnibus and The Cancer Genome Atlas. Combined in vitro and in silico analysis of promoter methylation levels of SPRY4 clearly demonstrates that the distal promoter region undergoes hypomethylation in CRC patients and is associated with increased expression. Moreover, a decrease in gene body hydroxymethylation and an increase in gene body methylation within the coding region of SPRY4 were found in CRC patients and correlated with increased expression. SPRY4 is epigenetically upregulated in CRC by promoter hypomethylation and hypermethylation within the gene body that warrants future investigation of atypical roles of this established tumor suppressor.

SPRY4 gene expression is increased in colorectal cancerThe SPRY4 promoter loses DNA methylation, and the gene body gains DNA methylation in colorectal cancerThe gene body of SPRY4 loses DNA hydroxymethylation.

Decreased serum superoxide dismutase concentration has a high value for the diagnosis of periprosthetic joint infection-a single-center, retrospective study.

PURPOSE: As the most serious complication of total knee arthroplasty (TKA), periprosthetic joint infection (PJI) often leads to disastrous consequences. An accurate preoperative diagnosis plays a significant role in saving prostheses and optimizing treatment outcomes. Through this retrospective case-control study, we aimed to investigate the potential of superoxide dismutase (SOD) as a novel serum biomarker in the diagnosis of PJI. METHODS: We conducted a retrospective review of all patients who underwent TKA and received adequate follow-ups in our hospital from June 2015 to December 2021. A total of 50 patients were enrolled in the PJI group based on the 2018 International Consensus Meeting (ICM) criteria. Besides that, we enrolled 100 patients who underwent TKA in the same period and had a good postoperative course in the control group. Patient characteristics, comorbidities, laboratory results (serum, synovial, and microbial), and intraoperative findings (purulence and histopathology) were documented and compared by univariate analysis. Receiver operating characteristic (ROC) analysis was used to determine the sensitivity, specificity, and diagnostic performance. RESULTS: The median serum SOD level in the PJI and control group was 135.95 ± 24.47 U/ml (IQR, 111.85-158.30 U/ml) and 173.83 ± 13.9 U/ml (IQR,162.83-183.5 U/ml) (p < 0.05), respectively. With the calculated cutoff of SOD at 149.5U/L, the area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were 0.919, 0.72, 0.97, 0.923, and 0.874, respectively. In subgroup analysis, the specificity of SOD in diagnosing culture-negative PJI remained extremely high (0.98). Combined diagnosis of serum SOD and C-reactive protein (CRP) made AUC increase to 0.972. CONCLUSION: Serum SOD showed great potential in the diagnosis of PJI.

Buffering the local pH via single-atomic Mn-N auxiliary sites to boost CO2 electroreduction.

Electrocatalytic CO2 reduction driven by renewable energy has become a promising approach to rebalance the carbon cycle. Atomically dispersed transition metals anchored on N-doped carbon supports (M-N-C) have been considered as the most attractive catalysts to catalyze CO2 to CO. However, the sluggish kinetics of M-N-C limits the large-scale application of this type of catalyst. Here, it is found that the introduction of single atomic Mn-N auxiliary sites could effectively buffer the locally generated OH- on the catalytic interface of the single-atomic Ni-N-C sites, thus accelerating proton-coupled electron transfer (PCET) steps to enhance the CO2 electroreduction to CO. The constructed diatomic Ni/Mn-N-C catalysts show a CO faradaic efficiency of 96.6% and partial CO current density of 13.3 mA cm-2 at -0.76 V vs. RHE, outperforming that of monometallic single-atomic Ni-N-C or Mn-N-C counterparts. The results suggest that constructing synergistic catalytic sites to regulate the surface local microenvironment might be an attractive strategy for boosting CO2 electroreduction to value-added products.

Linkage analysis and residual heterozygotes derived near isogenic lines reveals a novel protein quantitative trait loci from a Glycine soja accession.

Modern soybean [Glycine max (L.) Merr] cultivars have low overall genetic variation due to repeated bottleneck events that arose during domestication and from selection strategies typical of many soybean breeding programs. In both public and private soybean breeding programs, the introgression of wild soybean (Glycine soja Siebold and Zucc.) alleles is a viable option to increase genetic diversity and identify new sources for traits of value. The objectives of our study were to examine the genetic architecture responsible for seed protein and oil using a recombinant inbred line (RIL) population derived from hybridizing a G. max line ('Osage') with a G. soja accession (PI 593983). Linkage mapping identified a total of seven significant quantitative trait loci on chromosomes 14 and 20 for seed protein and on chromosome 8 for seed oil with LOD scores ranging from 5.3 to 31.7 for seed protein content and from 9.8 to 25.9 for seed oil content. We analyzed 3,015 single F4:9 soybean plants to develop two residual heterozygotes derived near isogenic lines (RHD-NIL) populations by targeting nine SNP markers from genotype-by-sequencing, which corresponded to two novel quantitative trait loci (QTL) derived from G. soja: one for a novel seed oil QTL on chromosome 8 and another for a novel protein QTL on chromosome 14. Single marker analysis and linkage analysis using 50 RHD-NILs validated the chromosome 14 protein QTL, and whole genome sequencing of RHD-NILs allowed us to reduce the QTL interval from ∼16.5 to ∼4.6 Mbp. We identified two genomic regions based on recombination events which had significant increases of 0.65 and 0.72% in seed protein content without a significant decrease in seed oil content. A new Kompetitive allele-specific polymerase chain reaction (KASP) assay, which will be useful for introgression of this trait into modern elite G. max cultivars, was developed in one region. Within the significantly associated genomic regions, a total of eight genes are considered as candidate genes, based on the presence of gene annotations associated with the protein or amino acid metabolism/movement. Our results provide better insights into utilizing wild soybean as a source of genetic diversity for soybean cultivar improvement utilizing native traits.

Atypical Adams-Oliver syndrome with typical ocular signs of familial exudative vitreoretinopathy.

AIM: To report an atypical Adams-Oliver syndrome (AOS) family with typical ocular signs of familial exudative vitreoretinopathy (FEVR). METHODS: A patient with visible avascular area and obvious non-perfusion zone in the peripheral retina with systemic signs of AOS was reported. Familial and personal characteristics were collected for the patient and his sister. Gene sequencing and ophthalmic examinations including fluorescein angiography were all performed for the whole family. RESULTS: Two novel mutations of DOCK6 (c.1396C>T and c.4796G>A) were identified in the proband and his family, and two compound heterozygous mutations were revealed in the proband and his sister. The patient and his sister showed physical deformities and mental abnormalities while FEVR mimicking retinal disorder can also be defined. No remarkable ocular or systemic abnormality can be observed for their parents. Peripheral retinal non-perfusion area, obvious abnormal vascularization or even retinal fold were observed in the proband and his sister, while only small avascular zone was identified for their parents. CONCLUSION: This is the first genetic authenticated AOS case mimicked as FEVR with genetic sequencing of a family. For the patients with ocular phenotype of FEVR, further examination should be performed if the systemic or mental abnormalities exist.

A novel mutation of CYP4V2 gene associated with Bietti crystalline dystrophy complicated by choroidal neovascularization.

AIM: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy (BCD) proband in a Chinese family. METHODS: A Chinese female diagnosed with BCD complicated by bilateral choroidal neovascularization (CNV) and her parents underwent complete ophthalmic examinations, including fundus autofluorescence (AF), fundus photography (FP), fundus fluorescein angiography (FFA), visual field testing, full-field electroretinography (ERG), optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The sequencing of the CYP4V2 gene was performed to the whole family. RESULTS: Bilateral tiny glittering crystal-like deposits and differing extent of atrophy of the retinal pigment epithelium (RPE) were found in the posterior pole of her fundus. The diffuse hypo-fluorescence shown on AF images and window defects shown on FFA both indicated the atrophy of the RPE and choriocapillaris. OCT showed the thinning of the RPE and choriocapillaris layer, ellipsoid zone (EZ) band defect and CNV in both eyes. OCTA images proofed bilateral type 2 CNV. The visual field test showed central and paracentral scotoma. ERG showed a slightly decreased b-wave in scotopic ERG. Gene sequencing identified three mutations of the CYP4V2 gene, c.802_807del, c.810delT, and c.1388G>A. The mutation c.1388G>A was a novel substitution mutation. CONCLUSION: The novel mutation c.1388G>A may be a possible cause that could induce the clinical phenotype of BCD.