REC protein family expansion by the emergence of a new signaling pathway.

IMPORTANCE: We explore when and why large classes of proteins expand into new sequence space. We used an unsupervised machine learning approach to observe the sequence landscape of REC domains of bacterial response regulator proteins. We find that within-gene recombination can switch effector domains and, consequently, change the regulatory context of the duplicated protein.

Abnormalities of the contralateral eye in unilateral congenital anophthalmic or blind microphthalmic patients.

PURPOSE: To describe the prevalence, distribution, and features of anterior and posterior segment abnormalities in the contralateral eye in cases unilateral of anophthalmia and blind microphthalmia. METHODS: The medical records of patients with unilateral congenital anophthalmia and blind microphthalmia referred to Beijing Tongren Hospital between January 2017 and December 2021 were reviewed retrospectively to investigate the prevalence of abnormalities of the fellow eye. RESULTS: A total of 168 patients were included. Of these, 28 (16.7%) had fellow eye abnormalities, 4 (2.4%) with anterior segment involvement in the contralateral eye. All 28 had fundus abnormalities. The most common posterior segment finding was coloboma (7.7%), followed by optic nerve dysplasia (3.0%), familial exudative vitreoretinopathy (FEVR) or FEVR-like fundus (1.8%), morning glory disk anomaly (1.8%), and retinal nerve fiber layer defect (1.2%). High myopia fundus changes (0.6%), retinal folds (0.6%), maculopathy (0.6%), peripapillary staphyloma (0.6%), and Bergmeister optic disk (0.6%) were also noted. CONCLUSIONS: Patients with unilateral congenital anophthalmia or blind microphthalmia have a high probability of contralateral eye disease. The most common abnormality is coloboma.

Using the Random Forest Algorithm to Detect the Activity of Graves Orbitopathy.

PURPOSE: The aim of this study is to establish a random forest model to detect active and quiescent phases of patients with Graves Orbitopathy (GO). METHODS: A total of 243 patients (486 eyes) diagnosed with GO in Beijing TongRen hospital were included in the study. The Clinical Activity Score of GO was regarded as the golden standard, whereas sex, age, smoking status, radioactive I131 treatment history, thyroid nodules, thyromegaly, thyroid hormone, and Thyroid-stimulating hormone receptor antibodies were chosen as predictive characteristic variables in the model. The random forest model was established and compared with logistic regression analysis, Naive Bayes, and Support vector machine metrics. RESULTS: Our model has a sensitivity of 0.81, a specificity of 0.90, a positive predictive value of 0.87, a negative predictive value of 0.86, an F1 score of 0.85, and an out-of-bag error of 0.15. The random forest algorithm showed a more precise performance compared with 3 other models based on the area under receiver operating characteristic curve (0.92 versus 0.77 versus 0.76 versus 0.75) and accuracy (0.86 versus 0.71 versus 0.69 versus 0.66). CONCLUSIONS: By integrating these high-risk factors, the random forest algorithm may be used as a complementary method to determine the activity of GO, with accurate and reliable performance.

Transcriptome Analysis to Identify Responsive Genes under Sublethal Concentration of Bifenazate in the Diamondback Moth, Plutella xylostella (Linnaeus, 1758) (Lepidoptera: Plutellidae).

Bifenazate is a novel acaricide that has been widely used to control spider mites. Interestingly, we found bifenazate had a biological activity against the diamondback moth (Plutella xylostella), one of the most economically important pests on crucifer crops around the world. However, the molecular mechanisms underlying the response of P. xylostella to bifenazate treatment are not clear. In this study, we first estimated the LC30 dose of bifenazate for third-instar P. xylostella larvae. Then, in order to identify genes that respond to the treatment of this insecticide, the comparative transcriptome profiles were used to analyze the gene expression changes in P. xylostella larvae after exposure to LC30 of bifenazate. In total, 757 differentially expressed genes (DEGs) between bifenazate-treated and control P. xylostella larvae were identified, in which 526 and 231 genes were up-regulated and down-regulated, respectively. The further Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the xenobiotics metabolisms pathway was significantly enriched, with ten detoxifying enzyme genes (four P450s, five glutathione S-transferases (GSTs), and one UDP-Glucuronosyltransferase (UGT)) were up-regulated, and their expression patterns were validated by qRT-PCR as well. Interestingly, the present results showed that 17 cuticular protein (CP) genes were also remarkably up-regulated, including 15 CPR family genes. Additionally, the oxidative phosphorylation pathway was found to be activated with eight mitochondrial genes up-regulated in bifenazate-treated larvae. In contrast, we found some genes that were involved in tyrosine metabolism and purine pathways were down-regulated, indicating these two pathways of bifenazate-exposed larvae were significantly inhibited. In conclusion, the present study would help us to better understand the molecular mechanisms of sublethal doses of bifenazate detoxification and action in P. xylostella.

Different Characteristics of Orbital Soft Tissue Expansion in Graves Orbitopathy: Extraocular Muscle Expansion is Correlated to Disease Activity While Fat Tissue Volume With Duration.

This study aimed to describe the correlation between some clinical features and orbital soft tissue volume in Graves orbitopathy (GO). The authors collected computed tomography scans from 56 untreated GO patients and measured fat volume (FV), intraorbital and extraorbital FV (IFV, EFV), bony cavity volume (BV), and extraocular muscle volume (MV) of the 112 orbits by using Mimics software. The ratio of soft tissue volume and BV were used to eliminate the individual variations. Outcomes were compared among groups and were correlated with clinical data, including age, sex, clinical activity score, duration, serum TSH receptor antibody (TRAb) level, body mass index and smoking status. Multivariate linear regression showed that higher MV/BV is associated with higher CAS and TRAb level ( P< 0.001, 0.005, res p ectively). No relationship was found between MV/BV and duration, sex, age, and body mass index. IFV/BV was related to duration (ß=0.138, 95% confidence interval: 0.076-0.201, P <0.001), and did not correlate to clinical activity. IFV and MV are positively associated with exophthalmometry ( P =0.009, <0.001, respectively), while orbital bony volume (BV) is negatively correlated with exophthalmometry ( P =0.025). Results suggested TRAb level can impact the severity of GO mainly by affecting extraocular muscle rather than fat tissue. MV of GO is associated with disease activity, whereas IFV is correlated with duration and increases over time.

Correlation between extent of lacrimal gland prolapse and clinical features of thyroid-associated ophthalmopathy: a retrospective observational study.

BACKGROUND: Studies on the factors related to lacrimal gland prolapse (LGP) in patients with thyroid-associated ophthalmopathy (TAO) are limited. This study aimed to assess the factors associated with LGP on magnetic resonance imaging (MRI) and its relation to TAO activity . METHODS: Thirty-six patients (72 orbits) with inactive TAO (43 orbits, Clinical Activity Score [CAS] < 3) or active TAO (29 orbits, CAS ≥3) were investigated retrospectively. All patients underwent ophthalmic evaluation and orbital magnetic resonance imaging. The severity of LGP and proptosis and the extraocular muscle (EOM) volume were measured. LGP and related factors were assessed by correlational and linear regression analyses. The value of LGP for discriminating the activity of TAO was evaluated by receiver-operating characteristic curve analysis. RESULTS: The mean LGP was significantly higher in the active TAO group than in the inactive TAO group (P < 0.001). There were significant positive correlations between LGP severity and the CAS (r = 0.51, P < 0.001), proptosis (r = 0.72, P < 0.001), and EOM volume (superior rectus [r = 0.49, P < 0.001], inferior rectus [r = 0.47, P < 0.001], lateral rectus [r = 0.59, P < 0.001], medial rectus [r = 0.62, P < 0.001], superior oblique [r = 0.48, P < 0.001], and all EOMs [r = 0.59, P < 0.001]). Receiver-operating characteristic curve analysis revealed an LGP of 13.65 mm (area under the curve, 0.824; sensitivity, 79.3%; specificity, 81.4%) to be the cut-off value that differentiated active and inactive TAO. CONCLUSIONS: LGP measurements obtained from orbital magnetic resonance images were positively correlated with CAS, proptosis and EOM volume. The extent of LGP appears to be a good indicator of disease activity in patients with TAO.

NCs-Delivered Pesticides: A Promising Candidate in Smart Agriculture.

Pesticides have been used extensively in the field of plant protection to maximize crop yields. However, the long-term, unmanaged application of pesticides has posed severe challenges such as pesticide resistance, environmental contamination, risk in human health, soil degradation, and other important global issues. Recently, the combination of nanotechnology with plant protection strategies has offered new perspectives to mitigate these global issues, which has promoted a rapid development of NCs-based pesticides. Unlike certain conventional pesticides that have been applied inefficiently and lacked targeted control, pesticides delivered by nanocarriers (NCs) have optimized formulations, controlled release rate, and minimized or site-specific application. They are receiving increasing attention and are considered as an important part in sustainable and smart agriculture. This review discussed the limitation of traditional pesticides or conventional application mode, focused on the sustainable features of NCs-based pesticides such as improved formulation, enhanced stability under harsh condition, and controlled release/degradation. The perspectives of NCs-based pesticides and their risk assessment were also suggested in this view for a better use of NCs-based pesticides to facilitate sustainable, smart agriculture in the future.

Ecogenomics of Groundwater Phages Suggests Niche Differentiation Linked to Specific Environmental Tolerance.

Viruses are ubiquitous microbiome components, shaping ecosystems via strain-specific predation, horizontal gene transfer and redistribution of nutrients through host lysis. Viral impacts are important in groundwater ecosystems, where microbes drive many nutrient fluxes and metabolic processes; however, little is known about the diversity of viruses in these environments. We analyzed four groundwater plasmidomes (the entire plasmid content of an environment) and identified 200 viral sequences, which clustered into 41 genus-level viral clusters (approximately equivalent to viral genera) including 9 known and 32 putative new genera. We used publicly available bacterial whole-genome sequences (WGS) and WGS from 261 bacterial isolates from this groundwater environment to identify potential viral hosts. We linked 76 of the 200 viral sequences to a range of bacterial phyla, the majority associated with Proteobacteria, followed by Firmicutes, Bacteroidetes, and Actinobacteria. The publicly available WGS enabled mapping bacterial hosts to several viral sequences. The WGS of groundwater isolates increased the depth of host prediction by allowing host identification at the strain level. The latter included 4 viruses that were almost entirely (>99% query coverage, >99% identity) identified as integrated in the genomes of Pseudomonas, Acidovorax, and Castellaniella strains, resulting in high-confidence host assignments. Lastly, 21 of these viruses carried putative auxiliary metabolite genes for metal and antibiotic resistance, which might drive their infection cycles and/or provide selective advantage to infected hosts. Exploring the groundwater virome provides a necessary foundation for integration of viruses into ecosystem models where they are key players in microbial adaption to environmental stress. IMPORTANCE To our knowledge, this is the first study to identify the bacteriophage distribution in a groundwater ecosystem shedding light on their prevalence and distribution across metal-contaminated and background sites. Our study is uniquely based on selective sequencing of solely the extrachromosomal elements of a microbiome followed by analysis for viral signatures, thus establishing a more focused approach for phage identifications. Using this method, we detected several novel phage genera along with those previously established. Our approach of using the whole-genome sequences of hundreds of bacterial isolates from the same site enabled us to make host assignments with high confidence, several at strain levels. Certain phage genes suggest that they provide an environment-specific selective advantage to their bacterial hosts. Our study lays the foundation for future research on directed phage isolations using specific bacterial host strains to further characterize groundwater phages, their life cycles, and their effects on groundwater microbiome and biogeochemistry.

Identification, Characterization and High-Performance Liquid Chromatography Quantification for Process-Related Impurities in Abiraterone Acetate Bulk Drug.

During the synthesis of abiraterone acetate bulk drug in some laboratory batches, two unreported impurities were detected by high-performance liquid chromatography analysis at levels ranging from 0.05 to 0.10% according to the United States Pharmacopeia method. The structures of two impurities were characterized and confirmed by NMR and MS, which were proposed to be [3ß-acetoxy-16-(3ß-acetoxy-androsta-5,16-dien-17-yl)-17-(3-pyridyl)-androsta-5,16-di-ene] and [3ß-acetoxy-16-(3ß-acetoxy-androsta-5,16-dien-17-yl)-17-androsta-5,16-di-ene]. It was proved that these impurities come into being during the preparation process of penultimate intermediate (abiraterone). The newly developed LC-UV method was used to monitor the impurity profile in the penultimate intermediate (abiraterone), which was validated by its satisfactory specificity, precision, accuracy and sensitivity. The probable origin of the impurity was also discussed.

Effectiveness of Glaucoma Diagnostic Parameters from Spectral Domain-Optical Coherence Tomography of Myopic Patients.

BACKGROUND: Currently, spectral-domain optical coherence tomography (SD-OCT) appears to be a new type of glaucoma diagnostic tool. Thus, this study aimed to evaluate the effectiveness of glaucoma diagnostic parameters from SD-OCT of patients with different severities of myopia. METHODS: This was a cross-sectional study. A total of 248 participants (248 eyes) were enrolled, including 51 cases in the early primary open-angle glaucoma group, 79 cases in the control group (0.50 D to -0.50 D, excluding -0.50 D), 47 cases in the low-myopic group (-0.50 to -3.00 D, excluding -3.00 D), 43 cases in the moderate-myopic group (-3.00 to -6.00 D, excluding -6.00 D), and 28 cases in the high-myopic group (≤-6.00 D). All participants were examined using the Humphrey visual field test and SD-OCT. The SD-OCT parameters of the retinal nerve fiber layer (RNFL) and ganglion cell complex were analyzed statistically using the receiver operating characteristic curve and area under the curve (AUC). RESULTS: The AUC showed that the best parameters for the control and low-myopic groups were the inferior and inferior temporal RNFL thicknesses (AUC >0.94), respectively; for the moderate- and high-myopic groups, the best parameter was the temporal low RNFL thickness (AUC, 0.926 and 0.896, respectively). The AUC of the inferior parameters of the moderate-myopic group (0.864) was lower, ranked 15th among all RNFL parameters. When the sensitivity was fixed at 85%, the specificity of the inferior, superior, inferior temporal, and superior temporal quadrants was higher (>80%) in the control and low-myopic groups, while they were lower (20-60%) for the moderate- and high-myopia groups. The green color based on the OCT database was also less for the high-myopic group compared with that of other groups (P < 0.05). CONCLUSIONS: Glaucoma diagnostic parameters from SD-OCT were not clinically effective for the moderate- and high-myopic groups. The specificities were low. The moderate- and high-myopic groups require comprehensive analyses for the diagnoses of glaucoma. The SD-OCT database should be improved to better indicate the level of myopia based on the corresponding diopter readings.

Ferromagnetic resonance of a single magnetic nanowire measured with an on-chip microwave interferometer.

An on-chip microwave interferometer suitable for high-sensitivity nanoscale magnetic material characterization is proposed. The device cancels the background parasitic common mode noise automatically. The magnetization dynamics of a 240 nm wide, 5 µm long, and 70 nm thick single permalloy nanowire is investigated. Compared with a prototype device proposed previously, the proposed device has a more than 20 dB sensitivity improvement. Full wave three-dimensional simulation shows that the device has the capability of studying the fundamental physics of nanoscale magnetic devices.

Distinguishing the viability of a single yeast cell with an ultra-sensitive radio frequency sensor.

We propose and demonstrate a simple, ultra sensitive radio frequency (RF) sensor to detect a single yeast cell and distinguish its viability in a microfluidic channel. On-chip interference is used to cancel background probing signals to improve sensor sensitivity. Individual viable and nonviable yeast cells (approximately 5.83 +/- 0.85 microm in diameter) are measured with clear sensing and identification of these cells.