Altered functional connectivity of resting-state networks and the correlation with clinical characteristics in intermittent exotropia adult patients: a resting-state magnetic resonance imaging study.

BACKGROUND: The pathogenesis of intermittent exotropia (IXT) remains unclear. The study aims to investigate alterations of resting-state networks (RSNs) in IXT adult patients using resting-state functional magnetic resonance imaging (rs-fMRI) data to explore the potential neural mechanisms. METHODS: Twenty-six IXT adult patients and 22 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent fMRI scanning and ophthalmological examinations. Brain areas with significant functional connectivity (FC) differences between the IXT and HC groups were selected as regions of interest (ROI) and mean z-scores were calculated to control for individual differences. RESULTS: Compared with HCs, IXT patients exhibited altered FC in various brain regions within RSNs involved in binocular fusion, stereopsis, ocular movement, emotional processes and social cognition, including the default mode network (DMN), the dorsal attention network (DAN), the visual network (VN), the sensorimotor network (SMN), the executive control network (ECN), the frontoparietal network (FPN) and the auditory network (AN). The degree of exodeviation was positively correlated with FC value of left middle occipital gyrus (MOG) within the VN. Correspondingly, we found a negative correlation between the degree of exodeviation and the FC value of left angular gyrus (AG) within FPN (P < 0.05). The FNC analysis between different RSNs also provides evidence on visual-motor cortical plasticity. CONCLUSIONS: IXT patients showed widespread changes of brain activity within RSNs related to binocular fusion, stereopsis, oculomotor control, emotional processes, and social cognition. These findings extend our current understanding of the neuropathological mechanisms of IXT. TRIAL REGISTRATION: Beginning date of the trial: 2021-09-01. Date of registration:2021-07-18. Trial registration number: ChiCTR 2,100,048,852. Trial registration site: http://www.chictr.org.cn/index.aspx .

A retrospective comparative case series of efficacy and safety of radiofrequency thermocoagulation versus drug therapy in patients with trigeminal neuralgia: A clinical case report.

BACKGROUND: The trigeminal neuralgia (TN) is characterized by a unilateral, episodic, electric shock-like pain in the distribution of the trigeminal nerve. Both drug therapy and radiofrequency thermocoagulation (RT) are used to treat TN. OBJECTIVE: To compare the efficacy and safety of RT and drug therapy in patients with TN. METHODS: Between October 2020 and December 2022, 62 patients with TN were allocated to undergo TN treatment (group A) or drug therapy (group B). In group A, 30 patients received RT treatment, whereas 32 patients in group B receive drug treatment. Pain relief, clinical outcomes, and adverse events in both groups were evaluated. RESULTS: And significantly greater reduction in Visual Analogue Scale scores was noted in group A than in group B in the initial 2-week period (P < .05). The excellent rate was 93.3% (28/30) in group A, whereas it was 68.8% (22/32) in group B during the initial 2-week period (P < .05). A total of 62 patients were followed up at least 12 months, with a mean follow-up time of 14.5 months. But there were no statistically significant differences between the 2 groups at the final follow-up. A total of 24 patients had facial numbness in group A. In contrast, ten patients in group B complained of discomfort including sedation, dizziness, nausea, vomiting. During the follow-up period, 4 patients in group A and 6 patients in group B experienced recurrent pain. CONCLUSION: RT is a safety and effective treatment for patients with classic TN, providing more benefits of quicker pain relief and higher patient's satisfaction, compared with traditional drug therapy.

Metabolic profile changes of zebrafish larvae in the single- and co-exposures of microplastics and phenanthrene.

Microplastics (MPs) are ubiquitous in the environment, and can adsorb organic contaminants (OCs) and be taken by various microorganisms and organisms, which could eventually lead to risk to humans. In this study, the phenotypic changes and metabolic profile alternations of zebrafish in the single- and co-exposure of MPs and phenanthrene (Phe) were investigated. The results showed that significantly higher tail malformation rate and edema rate in zebrafish induced by MPs can be enhanced due to the co-existence of Phe. The metabolomic analysis revealed that both synergistic and antagonistic effects of MPs and Phe on the metabolic alternation of zebrafish larvae exist, since unique perturbations of metabolites or pathways were found in all of the three exposure scenarios. Based on Partial least squares-discriminant analysis, porphine, ribose, and L-glutamic acid were the most important metabolites resulting in the difference between the treated and control groups in the MP exposure, Phe exposure and co-exposure, respectively. Two dysregulated pathways namely d-glutamine and D-glutamate metabolism, and alanine, aspartate and glutamate metabolism were significantly affected in the co-exposure while not in either of the single exposure. These findings provide new insights into the toxic effects of MPs on aquatic organisms, and further studies on combined effects of MPs and OCs are suggested to be conducted.

Advances in the genetic etiology of female infertility.

Human reproduction is a complex process involving gamete maturation, fertilization, embryo cleavage and development, blastocyst formation, implantation, and live birth. If any of these processes are abnormal or arrest, reproductive failure will occur. Infertility is a state of reproductive dysfunction caused by various factors. Advances in molecular genetics, including cell and molecular genetics, and high-throughput sequencing technologies, have found that genetic factors are important causes of infertility. Genetic variants have been identified in infertile women or men and can cause gamete maturation arrest, poor quality gametes, fertilization failure, and embryonic developmental arrest during assisted reproduction technology (ART), and thus reduce the clinical success rates of ART. This article reviews clinical studies on repeated in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) failures caused by ovarian dysfunction, oocyte maturation defects, oocyte abnormalities, fertilization disorders, and preimplantation embryonic development arrest due to female genetic etiology, the accumulation of pathogenic genes and gene pathogenic loci, and the functional mechanism and clinical significance of pathogenic genes in gametogenesis and early embryonic development.

Towards Establishing Best Practice in the Analysis of Hydrogen and Deuterium by Atom Probe Tomography.

As hydrogen is touted as a key player in the decarbonization of modern society, it is critical to enable quantitative hydrogen (H) analysis at high spatial resolution and, if possible, at the atomic scale. H has a known deleterious impact on the mechanical properties (strength, ductility, toughness) of most materials that can hinder their use as part of the infrastructure of a hydrogen-based economy. Enabling H mapping including local hydrogen concentration analyses at specific microstructural features is essential for understanding the multiple ways that H affect the properties of materials including embrittlement mechanisms and their synergies. In addition, spatial mapping and quantification of hydrogen isotopes is essential to accurately predict tritium inventory of future fusion power plants thus ensuring their safe and efficient operation. Atom probe tomography (APT) has the intrinsic capability to detect H and deuterium (D), and in principle the capacity for performing quantitative mapping of H within a material's microstructure. Yet, the accuracy and precision of H analysis by APT remain affected by complex field evaporation behavior and the influence of residual hydrogen from the ultrahigh vacuum chamber that can obscure the signal of H from within the material. The present article reports a summary of discussions at a focused workshop held at the Max-Planck Institute for Sustainable Materials in April 2024. The workshop was organized to pave the way to establishing best practices in reporting APT data for the analysis of H. We first summarize the key aspects of the intricacies of H analysis by APT and then propose a path for better reporting of the relevant data to support interpretation of APT-based H analysis in materials.

A study of a loss system with priorities.

The Erlang loss formula, also known as the Erlang B formula, has been known for over a century and has been used in a wide range of applications, from telephony to hospital intensive care unit management. It provides the blocking probability of arriving customers to a loss system involving a finite number of servers without a waiting room. Because of the need to introduce priorities in many services, an extension of the Erlang B formula to the case of a loss system with preemptive priority is valuable and essential. This paper analytically establishes the consistency between the global balance (steady state) equations for a loss system with preemptive priorities and a known result obtained using traffic loss arguments for the same problem. This paper, for the first time, derives this known result directly from the global balance equations based on the relevant multidimensional Markov chain. The paper also addresses the question of whether or not the well-known insensitivity property of the Erlang loss system is also applicable to the case of a loss system with preemptive priorities, provides explanations, and demonstrates through simulations that, except for the blocking probability of the highest priority customers, the blocking probabilities of the other customers are sensitive to the service time distributions and that a larger service time variance leads to a lower blocking probability of the lower priority traffic.

Magnetically Enhanced Oxygen Evolution Reaction in Mild Alkaline Electrolytes by Building Catalysts on Magnetic Frame.

Under large current densities, the excessive hydroxide ion (OH) consumption hampers alkaline water splitting involving the oxygen evolution reaction (OER). High OH concentration (≈30 wt.%) is often used to enhance the catalytic activity of OER, but it also leads to higher corrosion in practical systems. To achieve higher catalytic activity in low OH concentration, catalysts on magnetic frame (CMF) are built to utilize the local magnetic convection induced from the host frame's magnetic field distributions. This way, a higher reaction rate can be achieved in relatively lower OH concentrations. A CMF model system with catalytically active CoFeOx nanograins grown on the magnetic Ni foam is demonstrated. The OER current of CoFeOx@NF receives ≈90% enhancement under 400 mT (900 mA cm-2 at 1.65 V) compared to that in zero field, and exhibits remarkable durability over 120 h. As a demonstration, the water-splitting performance sees a maximum 45% magnetic enhancement under 400 mT in 1 m KOH (700 mA cm-2 at 2.4 V), equivalent to the concentration enhancement of the same electrode in a more corrosive 2 m KOH electrolyte. Therefore, the catalyst-on-magnetic-frame strategy can make efficient use of the catalysts and achieve higher catalytic activity in low OH concentration by harvesting local magnetic convection.

Effects of slurry ice treatment on the physicochemical changes and proteome of large yellow croaker (Larimichthys crocea).

Large yellow croaker (Larimichthys crocea) is susceptible to oxidative denaturation during storage. This work is to investigate the quality alterations by analyzing its physicochemical changes and proteomics throughout preservation under refrigeration, frozen, and slurry ice (SI) conditions. Results revealed that the freshness of large yellow croaker, as evaluated by indicators such as total volatile basic nitrogen, total viable count, and thiobarbituric acid reactive substances, was well maintained while stored in the SI group. Meanwhile, the water distribution in the muscle tissue of group SI exhibited slower fluctuations, thereby preserving the integrity of fish muscle cells. Based on label-free proteomic analysis, a considerable downregulation was observed in the mitogen-activated protein kinase (MAPK) signaling pathway, indicating that SI decelerated this metabolic pathway and effectively delayed the deterioration of muscle. Therefore, the application of SI provides potential for maintaining the quality stability of large yellow croaker.

A Nomogram of Predicting Healthcare-Associated Infections in Burned Children.

BACKGROUND: Healthcare-associated infections (HAIs) are a common clinical concern associated with adverse prognosis and mortality in burned children. This study aimed to construct a predictive nomogram of the risk of HAIs in burned children. METHODS: Children admitted to the burn unit of Wuhan Third Hospital between 2020 and 2022 were included. The univariate and multivariate logistic regression analyses were adopted to ascertain predictors of HAIs. A nomogram was developed to predict the HAI risk of each patient, with receiver operating characteristic curves and calibration curves being generated to assess its predictive ability. Furthermore, decision and impact curves were used to assess the clinical utility. RESULTS: Of 1122 burned children, 61 (5.5%) patients experienced HAIs. The multivariate analysis indicated that total burn surface area, length of stay, surgery, central venous catheter use and urinary catheter use were the independent risk factors of HAIs. Using these variables, we developed a predictive nomogram of the occurrence of HAIs in burned children, and the internal validation results demonstrated good discrimination and calibration of the nomogram. The area under the curve values of the nomogram was 0.926 (95% CI, 0.896-0.957). The calibration curve showed high consistency between the actual and predicted HAIs. The decision and impact curve indicated that the nomogram was of good clinical utility and more credible net clinical benefits in predicting HAIs. CONCLUSIONS: The present study constructed a nomogram for predicting the risk of HAIs in burned children. This nomogram may strengthen the effective screening of patients at high risk of HAIs.

Population Pharmacokinetic Analysis and Dosing Optimization of Colistin Sulfate in Lung Transplant Recipients with Pneumonia: A Prospective Study.

OBJECTIVES: Currently, there is a lack of information on the clinical pharmacokinetics (PK), effectiveness, and safety of colistin sulfate in lung transplant recipients. This study aims to improve colistin sulfate dosing regimens and evaluate its population pharmacokinetics (PopPK) in lung transplant recipients. METHODS: This study evaluated the clinical efficacy, microbiological efficacy, and adverse events of colistin sulfate in lung transplant recipients. The NONMEM program was employed to construct the PopPK model, and Monte Carlo simulations were executed to establish dosing regimens according to the probability of target attainment (PTA). RESULTS: The study included 146 colistin sulfate concentrations, spanning from 0.05 to 4.18 mg/L from 39 lung transplant recipients with multidrug-resistant gram-negative bacteria. 26 (66.67%) patients successfully eradicated bacteria, and 30 (76.92%) patients had clinical cure or improvement. Additionally, only 2 (5.13%) patients developed colistin sulfate-related nephrotoxicity. The PK profile was effectively represented by a one-compartmental model with linear elimination. Creatinine clearance (CrCL) and concomitant furosemide use were recognized as covariates influencing the clearance of colistin sulfate. Based on the PTA results, a daily dosage of 1.5 million IU, divided into 2-3 administrations, could attain a PTA exceeding 90% for MIC ≤ 1 µg/mL at CrCL of about 110 mL/min. However, this regimen would lead to insufficient exposure for MIC ≥ 2 µg/mL. CONCLUSION: The clearance of colistin sulfate is significantly influenced by concomitant furosemide use and renal function. The currently recommended dosing regimens by label sheet may result in subtherapeutic exposure for MIC exceeding 1 mg/L in lung transplant recipients.

Association of Accommodation and Convergence with Axial Length Elongation in Children with Basic Intermittent Exotropia: A 12-Month Observational Study.

INTRODUCTION: The aim of the study was to investigate the association of parameters related to accommodation and convergence and axial elongation in basic intermittent exotropia (IXT) patients and the potential clinical predictors of axial length (AL) growth. METHODS: A total of 140 basic IXT patients were recruited in this study. The medians of AL growth in different age brackets were chosen to divide the subjects into group A (slower axial elongation group, n = 69) and group B (faster axial elongation group, n = 71). Parameters of dominant and nondominant eyes were compared and analyzed during the 12-month follow-up period. The parameters, including baseline refraction, angle of deviation, Newcastle control score (NCS), accommodative amplitude (AMP), accommodative facility (AMF), accommodative response, positive or negative relative accommodation (PRA/NRA), and near point of convergence (NPC), were analyzed via univariate and multivariate regression. RESULTS: Subjects in the faster axial elongation group tended to have more myopic spherical equivalents (t = 3.956, p < 0.001), greater AMPs of dominant eyes (t = -2.238, p = 0.027), and fewer near points of convergence (t = 2.347, p = 0.020) than in the slower axial elongation group. For dominant eyes, logistic and linear regression analysis revealed that more negative spherical equivalents (OR = 0.603, p < 0.001; ß = -0.045, p < 0.001), greater AMPs (OR = 1.201, p = 0.027; ß = 0.023, p = 0.010), and less near points of convergence (OR = 0.883, p = 0.021; ß = -0.012, p = 0.019) were correlated with the faster axial elongation. For nondominant eyes, a more myopic spherical equivalent (OR = 0.682; p = 0.001; ß = -0.029, p = 0.005) was the only parameter correlated with faster axial elongation through regression analysis. CONCLUSION: In children with basic IXT, faster axial elongation in the dominant eyes was associated with more myopic spherical equivalents, greater AMPs, and lower NPCs. These accommodative parameters can serve as potential clinical indicators for monitoring myopia progression in addition to AL.

Synthetic, marine, light-driven, autotroph-heterotroph co-culture system for sustainable ß-caryophyllene production.

Applying low-cost substrate is critical for sustainable bioproduction. Co-culture of phototrophic and heterotrophic microorganisms can be a promising solution as they can use CO2 and light as feedstock. This study aimed to create a light-driven consortium using a marine cyanobacterium Synechococcus sp. PCC 7002 and an industrial yeast Yarrowia lipolytica. First, the cyanobacterium was engineered to accumulate and secrete sucrose by regulating the expression of genes involved in sucrose biosynthesis and transport, resulting in 4.0 g/L of sucrose secretion. Then, Yarrowia lipolytica was engineered to efficiently use sucrose and produce ß-caryophyllene that has various industrial applications. Then, co- and sequential-culture were optimized with different induction conditions and media compositions. A maximum ß-caryophyllene yield of 14.1 mg/L was obtained from the co-culture. This study successfully established an artificial light-driven consortium based on a marine cyanobacterium and Y. lipolytica, and provides a foundation for sustainable bioproduction from CO2 and light through co-culture systems.

AT-hook motif nuclear localized transcription factors function redundantly in promoting root growth through modulation of redox homeostasis.

Maintaining an optimal redox status is essential for plant growth and development, particularly when the plants are under stress. AT-hook motif nuclear localized (AHL) proteins are evolutionarily conserved transcription factors in plants. Much of our understanding about this gene family has been derived from studies on clade A members. To elucidate the functions of clade B genes, we first analyzed their spatial expression patterns using transgenic plants expressing a nuclear localized GFP under the control of their promoter sequences. AHL1, 2, 6, 7, and 10 were further functionally characterized owing to their high expression in the root apical meristem. Through mutant analyses and transgenic studies, we showed that these genes have the ability to promote root growth. Using yeast one-hybrid and dual luciferase assays, we demonstrated that AHL1, 2, 6, 7, and 10 are transcription regulators and this activity is required for their roles in root growth. Although mutants for these genes did not showed obvious defects in root growth, transgenic plants expressing their fusion proteins with the SRDX repressor motif exhibited a short-root phenotype. Through transcriptome analysis, histochemical staining and molecular genetics experiments, we found that AHL10 maintains redox homeostasis via direct regulation of glutathione transferase (GST) genes. When the transcript level of GSTF2, a top-ranked target of AHL10, was reduced by RNAi, the short-root phenotype in the AHL10-SRDX expressing plant was largely rescued. These results together suggest that AHL genes function redundantly in promoting root growth through direct regulation of redox homeostasis.

A clearer vision: unveiling the importance of cycloplegic refraction and the pseudomyopia prevalence in Chinese preschoolers.

BACKGROUND: This study aimed to investigate the difference between cycloplegic and noncycloplegic refraction and evaluate the pseudomyopia prevalence in Chinese preschool children during the outbreak of COVID-19. METHODS: A cross-sectional study was conducted in the Tongzhou District of Beijing, China. Refractive error was measured under both noncycloplegic and cycloplegic conditions with autorefraction. The difference between noncycloplegic and cycloplegic spherical equivalent refraction (SER) and pseudomyopia prevalence were analyzed. Pseudomyopia was defined as SER ≤-0.50D in precycloplegic assessments and >-0.50D in post-cycloplegic assessments. RESULTS: Out of the 1487 participants who were enrolled in the study, 1471 individuals (98.92%) between the ages of 3-6 years completed all required procedures. A statistically significant difference in refraction was observed between noncycloplegic and cycloplegic measurements, the median of difference in spherical equivalent refraction (SER) of 0.88D (dioptre)(0.50,1.38). There was a high intraclass correlation (ICC) between these two methods for cylinders (ICC = 0.864; 95% CI, 0.850-0.877). The median DSE for myopia, emmetropia and hyperopia were 0.25D (0.00, 0.38),0.25D (0.06, 0.50) and 1.00D (0.62, 1.38), an hypermetropes showed considerably greater differences than myopes and emmetropes (Kruskal-Wallis test, H = 231.023, P = 0.000). Additionally, girls displayed a greater DSE than boys. Furthermore, when comparing against-the-rule (ATR) and oblique astigmatism, it was found that with-the-rule (WTR) astigmatism had the largest DSE. The study found varying prevalence rates of myopia, emmetropia, and hyperopia with and without cycloplegia, which were 1.90% vs. 10.06%, 11.49% vs. 50.31%, and 86.61% vs. 39.63%, respectively. Additionally, the overall prevalence of pseudomyopia was determined to be 8.29%. Participants with pseudomyopia had a significantly higher mean difference in SER (DSE) compared to non-pseudomyopic participants. CONCLUSIONS: Cycloplegic refraction is more sensitive than a noncycloplegic one for measuring refractive error in preschool children. Pseudomyopia is prevalent in preschool children during the COVID-19 outbreak period. Our study indicates the possibility that cycloplegic refraction should be performed in preschool children routinely.

Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations.

The liver possesses a distinctive capacity for regeneration within the human body. Under normal circumstances, liver cells replicate themselves to maintain liver function. Compensatory replication of healthy hepatocytes is sufficient for the regeneration after acute liver injuries. In the late stage of chronic liver damage, a large number of hepatocytes die and hepatocyte replication is blocked. Liver regeneration has more complex mechanisms, such as the transdifferentiation between cell types or hepatic progenitor cells mediated. Dysregulation of liver regeneration causes severe chronic liver disease. Gaining a more comprehensive understanding of liver regeneration mechanisms would facilitate the advancement of efficient therapeutic approaches. This review provides an overview of the signalling pathways linked to different aspects of liver regeneration in various liver diseases. Moreover, new knowledge on cellular interactions during the regenerative process is also presented. Finally, this paper explores the potential applications of new technologies, such as nanotechnology, stem cell transplantation and organoids, in liver regeneration after injury, offering fresh perspectives on treating liver disease.

A acute pontine infarction with one-and-a-half syndrome as the manifestation: A case report.

RATIONALE: Sudden ocular dyskinesia is usually associated with ophthalmic diseases and rarely with cerebrovascular diseases. This is a rare case of a patient with a sudden onset of ocular dyskinesia due to occlusion of the anterior inferior cerebellar artery and the spiral modiolar artery. This article describes eye movement disorders associated with cerebrovascular disease, aiming to improve our understanding of cerebrovascular diseases and improve the ability of early diagnosis and differential diagnosis. PATIENT CONCERNS: A 52-year-old man presented with acute pontine cerebral infarction 2 days before presentation. The main symptoms were the inability to adduct and abduct the left eyeball, the ability to abduct but not adduct the right eyeball, and horizontal nystagmus during abduction. Cranial computed tomography in our emergency department suggested cerebral infarction, and magnetic resonance imaging examination after admission confirmed the diagnosis of acute pontine cerebral infarction. DIAGNOSIS: This patient was ultimately diagnosed with acute pontine cerebral infarction. INTERVENTIONS: He received aspirin, clopidogrel, and butylphthalide, as well as acupuncture and Chinese herbal medicine. OUTCOMES: After 10 days of treatment, the patient's paralysis of the eye muscles improved significantly. LESSONS: Eye movement disorders are sometimes an early warning sign of impending vertebrobasilar ischemic stroke. Patients with acute ischemic stroke who have early detection of oculomotor disturbances should be promptly imaged, as missed diagnosis may lead to serious consequences or even death. It provided us with a new diagnostic idea.

Reprogramming Yarrowia lipolytica metabolism for efficient synthesis of itaconic acid from flask to semipilot scale.

Itaconic acid is an emerging platform chemical with extensive applications. Itaconic acid is currently produced by Aspergillus terreus through biological fermentation. However, A. terreus is a fungal pathogen that needs additional morphology controls, making itaconic acid production on industrial scale problematic. Here, we reprogrammed the Generally Recognized As Safe (GRAS) yeast Yarrowia lipolytica for competitive itaconic acid production. After preventing carbon sink into lipid accumulation, we evaluated itaconic acid production both inside and outside the mitochondria while fine-tuning its biosynthetic pathway. We then mimicked the regulation of nitrogen limitation in nitrogen-replete conditions by down-regulating NAD+-dependent isocitrate dehydrogenase through weak promoters, RNA interference, or CRISPR interference. Ultimately, we optimized fermentation parameters for fed-batch cultivations and produced itaconic acid titers of 130.1 grams per liter in 1-liter bioreactors and 94.8 grams per liter in a 50-liter bioreactor on semipilot scale. Our findings provide effective approaches to harness the GRAS microorganism Y. lipolytica for competitive industrial-scale production of itaconic acid.