INOS ablation promotes corneal wound healing via activation of Akt signaling.

Corneal injury leads to impaired normal structure of the cornea. Improving the wound healing process in epithelial cells significantly contributes to ocular damage treatments. Here, we aimed to investigate the potential mechanisms of nitric oxide (NO) and its mediator, inducible nitric oxide synthase (iNOS), in the process of corneal wound healing. We established a corneal injury model of iNOS-/- mice, and treated human corneal epithelial cell lines (HCE-2) with the iNOS inhibitor L-INL, with or without NO replenishment by supplying sodium nitroferricyanide dihydrate (SNP). Our findings showed that inhibition of NO/iNOS accelerated corneal repair, enhanced uPAR (a receptor protein indicating the migration ability), and improved epithelial cell migration. Furthermore, NO/iNOS ablation activated Akt phosphorylation, reduced neutrophil marker protein MPO expression, and downregulated the transcription of inflammation cytokines CXCL-1, CXCL-2, IL-1ß, IL-6, and TNF-α. However, the protective effects of NO/iNOS inhibition are significantly reduced by NO replenishment when treated with SNP. Therefore, we confirmed that inhibiting NO/iNOS improved the corneal wound healing by facilitating epithelial cell migration and reducing inflammatory reactions, which might be related to the activation of the Akt signaling pathway.

Relationship between the structure and microcirculation of the optic disc region and myopic traction maculopathy in highly myopic eyes.

PURPOSE: To explore the characteristics and influencing factors structural and microcirculatory of optic disc and peripapillary tissue in eyes with myopia traction maculopathy (MTM). METHODS: There were 100 eyes from 77 patients in this study. We used 1:1 matching axial length in myopic eyes. Patients were divided into two groups according to the presence or absence of MTM. Fundus structure parameters were obtained by swept source optical coherence tomography (SS-OCT), and the optic disc microcirculation parameters were obtained by OCT angiography (OCTA). RESULTS: MTM group were older (P = 0.001) and had poorer Best-corrected Visual Acuity (BCVA) (P = 0.011), the optic disc-fovea distance (DFD) was longer (P < 0.019), optic disc tilt was greater (P < 0.001), area of peripapillary atrophy (PPA) was larger (P < 0.001), and PPA/optical disc area (ONH) was higher (P < 0.001). The peripapillary scleral thickness (PST) was lower in the MTM group (P < 0.001). The mean peripapillary choroidal thickness (PCT) (P < 0.001) and PCT in the 10 orientations were significantly lower in the MTM group than in the NMTM group (all P < 0.01). Vascular density in the nasosuperior (NS) region of the optic disc was significantly lower in the MTM group (P = 0.037). The generalized estimating equation suggested that PPA area (P = 0.028), mean PCT (P = 0.008), superior PCT (P = 0.027), inferonasal PCT (P = 0.040), temporoinferior PCT (P = 0.013), and PST (P = 0.046) correlated with MTM. Age, axial length, optic disc tilt, PPA area, mean PCT, and optic disc central zone (0-2 mm) vascular density (all P < 0.05) were significantly correlated with PST. CONCLUSIONS: The enlarged PPA area and thinner PCT and PST in eyes with MTM are more significant. Lower PST in high myopia was related to abnormalities of PCT and microcirculation. TRIAL REGISTRATION: Clinical Trial Registration number: ChiCTR2100046590.

Morphological characteristics of the foveal avascular zone in pathological myopia and its relationship with macular structure and microcirculation.

PURPOSE: To explore the characteristics of macular structure, microcirculation, and foveal avascular zone (FAZ) morphology in pathological myopia and to research the associations between these factors and pathological myopia. METHODS: This is a cross-sectional study. The study included 103 eyes with non-high myopia and 206 eyes with high myopia (139 with simple high myopia and 67 with pathological myopia). Macular structural and microcirculation parameters were determined using optical coherence tomography angiography (OCTA). The FAZ morphological parameters were measured manually using Image J software. Correlations between pathological myopia and various factors were analyzed. RESULTS: Patients with pathological myopia had a thinner retinal thickness (RT) and choroidal thickness (CT) and a lower retinal superficial vascular density (SVD), retinal deep vascular complex density (DVD), choriocapillaris perfusion area (CCPA), and choroidal vascularity index (CVI) (all P < 0.05). Patients with pathological myopia had a larger FAZ area, perimeter, major axis, minor axis, acircularity index (AI), and lower circularity index (CI) (all P < 0.01). The axial length (AL), the major axis of the superficial FAZ, CI, and AI were significantly correlated with myopia severity (all P < 0.05). CONCLUSIONS: Patients with pathological myopia exhibited worse macular microcirculation and thinner macular retina and choroid. The FAZ in pathological myopia was larger and more irregular. The AL, CI, and AI were significantly associated with myopia severity. Thus, CI and AI might serve as new indicators for monitoring the progression of myopia. Further investigations should be performed. TRIAL REGISTRATION: Clinical Trials.gov Identifier: ChiCTR2100046590.

Evaluating the microcirculation of the dome-shaped macula and its complications in adults with highly myopic eyes by swept-source optical coherence tomography angiography.

PURPOSE: The aim of this study was to investigate the microcirculatory characteristics of the dome-shaped macula (DSM), its complications in highly myopic eyes and to explore the factors associated with a DSM. METHODS: This cross-sectional case-control study included a total of 98 subjects (98 eyes): 49 eyes with DSM and 49 eyes without DSM. The axial length (AL) of the myopic eyes was matched 1:1 to eliminate the effect of AL differences on the results. Choroidal (CT) and scleral thickness (ST) and other structural parameters were assessed by swept-source optical coherence tomography (SS-OCT). OCT angiography was used to measure microcirculatory parameters in highly myopic eyes. RESULTS: Subjects with DSM had thinner subfoveal choroidal thickness (46.01 ± 13.25 vs. 81.62 ± 48.26 µm; p < 0.001), thicker subfoveal scleral thickness (SFST; 331.93 ± 79.87 vs. 238.74 ± 70.96 µm; p < 0.001) and thinner foveal CT (66.86 ± 24.65 vs. 107.85 ± 52.65 µm; p < 0.001) compared to subjects without DSM. The foveal choroidal perfusion area (0.72 ± 0.04 vs. 0.76 ± 0.04 mm2; p < 0.001) and foveal choroidal vascularity index (0.15 ± 0.04 vs. 0.33 ± 0.14; p < 0.001) were significantly lower in eyes with DSM. Retinoschisis (81.6% vs. 38.8%; p < 0.001) was more common in eyes with DSM. Eyes with horizontal DSM had worse best-corrected logMAR visual acuity than eyes with round DSM (0.34 ± 0.22 vs. 0.23 ± 0.22; p = 0.03). DSM height (98.95 ± 65.17 vs. 104.63 ± 44.62 µm; p = 0.05) was lower in the horizontal DSM. SFST (OR = 1.06, p = 0.04) and foveal choroidal vascularity index (OR = 0.711, p = 0.02) were significantly associated with DSM. DSM width (p < 0.001), foveal choroidal perfusion area (p = 0.01), foveal choriocapillaris perfusion area (p = 0.02) and parafoveal choroidal vascularity index (p = 0.03) were the most significantly associated factors with DSM height. CONCLUSIONS: The microcirculatory characteristics of eyes with DSM differed from those without DSM. Microcirculatory abnormalities were significantly associated with a DSM. The height of the DSM was associated with decreased blood perfusion.

Retinal and choroidal structure and vascularity in Chinese emmetropic and myopic children.

PURPOSE: This study evaluated the structural features of the retinal and choroidal regions and their correlations with ocular biometric and vascular parameters in Chinese children using optical coherence tomography angiography (OCTA). METHODS: A total of 159 children, 6-13 years of age, were included in this prospective study. The sample consisted of 55 emmetropes (spherical equivalent ≤ +0.75 and > -0.50 D), 53 low-moderate myopes (≤ -0.50 to > -6.00 D) and 51 high myopes without pathological changes (≤ -6.00 D). Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Swept-source optical coherence tomography/OCTA was used to assess the macular structures and vascular characteristics in a 6 × 6 mm region centred on the macula. RESULTS: In a comprehensive analysis adjusting for age, sex, AL, macular blood perfusion, intraocular pressure and anterior segment parameters, retinal thickness (RT) showed a significant positive association with deep retinal vascular density and superficial retinal vascular density in the foveal area, but not with AL. Moreover, RT exhibited a significant negative association with AL in the parafoveal and perifoveal regions. Further, a significant positive correlation was observed between choroidal thickness and both choroidal vascular volume and choriocapillaris perfusion area, along with a negative correlation with AL across the entire macular region. CONCLUSIONS: This study showed that the thickness of retina and choroid in Chinese children was not only associated with AL but also showed dynamic properties such as the blood perfusion of the retina and choroid, particularly in the foveal area.

Cerebello-cerebral resting-state functional connectivity in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder characterized by progressive motor and nonmotor deficits concomitant with degenerative pathophysiological changes within the cerebellum. The cerebellum is topographically organized into cerebello-cerebral circuits that create distinct functional networks regulating movement, cognition, and affect. SCA3-associated motor and nonmotor symptoms are possibly related not only to intracerebellar changes but also to disruption of the connectivity within these cerebello-cerebral circuits. However, to date, no comprehensive investigation of cerebello-cerebral connectivity in SCA3 has been conducted. The present study aimed to identify cerebello-cerebral functional connectivity alterations and associations with downstream clinical phenotypes and upstream topographic markers of cerebellar neurodegeneration in patients with SCA3. This study included 45 patients with SCA3 and 49 healthy controls. Voxel-based morphometry and resting-state functional magnetic resonance imaging (MRI) were performed to characterize the cerebellar atrophy and to examine the cerebello-cerebral functional connectivity patterns. Structural MRI confirmed widespread gray matter atrophy in the motor and cognitive cerebellum of patients with SCA3. We found reduced functional connectivity between the cerebellum and the cerebral cortical networks, including the somatomotor, frontoparietal, and default networks; however, increased connectivity was observed between the cerebellum and the dorsal attention network. These abnormal patterns correlated with the CAG repeat expansion and deficits in global cognition. Our results indicate the contribution of cerebello-cerebral networks to the motor and cognitive impairments in patients with SCA3 and reveal that such alterations occur in association with cerebellar atrophy. These findings add important insights into our understanding of the role of the cerebellum in SCA3.

Assessment of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with high myopia.

BACKGROUND: Previous reports have suggested that inflammation levels play a crucial role in the pathogenesis of high myopia (HM). This study aimed to investigate the relationship between HM and systemic inflammation using the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). METHODS: Overall, 100 age- and sex-matched participants were recruited for the study, including 50 participants each in the non-HM (NHM) and HM groups. Ocular examinations and blood tests were performed. The NLR and PLR values were calculated from complete blood counts. Receiver operating characteristic (ROC) curves and optimal cut-off values were used to determine the optimal values of the NLR and PLR to distinguish between the HM and NHM groups. RESULTS: The values of NLR and PLR were significantly elevated in the HM group compared with those in the NHM group (P < 0.001 and P = 0.010, respectively). Axial length (AL) was significantly correlated with the NLR (r = 0.367, P < 0.001) and PLR (r = 0.262, P = 0.009). In the ROC analysis, the NLR value to distinguish between the HM and NHM groups was 0.728; the best cut-off value was 2.68, with 76% sensitivity and 62% specificity. The PLR value to distinguish between the HM and NHM groups was 0.650; the best cut-off value was 139.69, with 52% sensitivity and 76% specificity. CONCLUSION: The findings of this study indicate that the development of HM may be associated with systemic inflammation measured using the NLR and PLR. TRIAL REGISTRATION: The study was registered on December 28, 2021 ( http://www.chictr.org.cn ; ChiCTR2100054834).

Individual-specific functional connectome biomarkers predict schizophrenia positive symptoms during adolescent brain maturation.

Even with an overarching functional dysconnectivity model of adolescent-onset schizophrenia (AOS), there have been no functional connectome (FC) biomarkers identified for predicting patients' specific symptom domains. Adolescence is a period of dramatic brain maturation, with substantial interindividual variability in brain anatomy. However, existing group-level hypotheses of AOS lack precision in terms of neuroanatomical boundaries. This study aimed to identify individual-specific FC biomarkers associated with schizophrenic symptom manifestation during adolescent brain maturation. We used a reliable individual-level cortical parcellation approach to map functional brain regions in each subject, that were then used to identify FC biomarkers for predicting dimension-specific psychotic symptoms in 30 antipsychotic-naïve first-episode AOS patients (recruited sample of 39). Age-related changes in biomarker expression were compared between these patients and 31 healthy controls. Moreover, 29 antipsychotic-naïve first-episode AOS patients (analyzed sample of 25) were recruited from another center to test the generalizability of the prediction model. Individual-specific FC biomarkers could significantly and better predict AOS positive-dimension symptoms with a relatively stronger generalizability than at the group level. Specifically, positive symptom domains were estimated based on connections between the frontoparietal control network (FPN) and salience network and within FPN. Consistent with the neurodevelopmental hypothesis of schizophrenia, the FPN-SN connection exhibited aberrant age-associated alteration in AOS. The individual-level findings reveal reproducible FPN-based FC biomarkers associated with AOS positive symptom domains, and highlight the importance of accounting for individual variation in the study of adolescent-onset disorders.

TAR DNA-binding protein 43 (TDP-43) liquid-liquid phase separation is mediated by just a few aromatic residues.

Eukaryotic cells contain distinct organelles, but not all of these compartments are enclosed by membranes. Some intrinsically disordered proteins mediate membraneless organelle formation through liquid-liquid phase separation (LLPS). LLPS facilitates many biological functions such as regulating RNA stability and ribonucleoprotein assembly, and disruption of LLPS pathways has been implicated in several diseases. Proteins exhibiting LLPS typically have low sequence complexity and specific repeat motifs. These motifs promote multivalent connections with other molecules and the formation of higher-order oligomers, and their removal usually prevents LLPS. The intrinsically disordered C-terminal domain of TAR DNA-binding protein 43 (TDP-43), a protein involved in motor neuron disease and dementia lacks a dominant LLPS motif, however, and how this domain forms condensates is unclear. Using extensive mutagenesis of TDP-43, we demonstrate here that three tryptophan residues and, to a lesser extent, four other aromatic residues are most important for TDP-43 to undergo LLPS. Our results also suggested that only a few residues may be required for TDP-43 LLPS because the α-helical segment (spanning ∼20 residues) in the middle part of the C-terminal domain tends to self-assemble, reducing the number of motifs required for forming a multivalent connection. Our results indicating that a self-associating α-helical element with a few key residues regulates condensate formation highlight a different type of LLPS involving intrinsically disordered regions. The C-terminal domain of TDP-43 contains ∼50 disease-related mutations, with no clear physicochemical link between them. We propose that they may disrupt LLPS indirectly by interfering with the key residues identified here.

The physical forces mediating self-association and phase-separation in the C-terminal domain of TDP-43.

The TAR DNA-binding protein of 43kDa (TDP-43) has been identified as the main component of amyotrophic lateral sclerosis (ALS) cytoplasmic inclusions. The link between this proteinopathy and TDP-43's intrinsically disordered C-terminal domain is well known, but recently also, this domain has been shown to be involved in the formation of the membraneless organelles that mediate TDP-43's functions. The mechanisms that underpin the liquid-liquid phase separation (LLPS) of these membraneless organelles undergo remain elusive. Crucially though, these factors may be the key to understanding the delicate balance between TDP-43's physiological and pathological functions. In this study, we used nuclear magnetic resonance spectroscopy and optical methods to demonstrate that an α-helical component in the centre (residues 320-340) of the C-terminal domain is related to the protein's self-association and LLPS. Systematically analysing ALS-related TDP-43 mutants (G298S, M337V, and Q331K) in different buffer conditions at different temperatures, we prove that this phase separation is driven by hydrophobic interactions but is inhibited by electrostatic repulsion. Based on these findings, we rationally introduced a mutant, W334G, and demonstrate that this mutant disrupts LLPS without disturbing this α-helical propensity. This tryptophan may serve as a key residue in this protein's LLPS.

[Molecular basis of an individual with CisAB subtype of ABO blood group].

OBJECTIVE: To explore the molecular basis for an individual with CisAB subtype of the ABO blood group. METHODS: ABO antigen and serum antibody of the proband were detected with a serological method. Exons 5 to 7 of the ABO gene were amplified with PCR and sequenced bidirectionally. Allele-specific amplification for exon 6 to 7 was also carried out. RESULTS: The proband was assigned as a CisAB phenotype based on his serological characteristics. Heterozygous variations including 220C/T, 261G/del, 297A/G, 467C/T, 646A/T, 681A/G, 771C/T, 803G/C, 829A/G and 1009A/G of the ABO gene were identified through direct sequencing, which was assigned as CisAB01var/O02 genotype. Allele-specific amplification indicated that the proband carried an O02 allele and a CisAB01var allele. Compared with A102, the CisAB01var allele has two nucleotide substitutions at 803G>C and 1009A>G, which resulted in replacement of amino acid Gly by Ala at position 268 and Arg by Gly at position 337. CONCLUSION: The CisAB subtype was identified with 803G>C and 1009A>G variants in the α1,3-N-acetyl-galactosaminyltransferase gene compared with that of the A102 allele.

Ionomic and metabolic responses to neutral salt or alkaline salt stresses in maize (Zea mays L.) seedlings.

BACKGROUND: Soil salinity and alkalinity present a serious threat to global agriculture. However, most of the studies have focused on neutral salt stress, and the information on the metabolic responses of plants to alkaline salt stress is limited. This investigation aimed at determining the influence of neutral salt and alkaline salt stresses on the content of metal elements and metabolites in maize plant tissues, by using mixtures of various proportions of NaCl, NaHCO3, Na2SO4, and Na2CO3. RESULTS: We found that alkaline salt stress suppressed more pronouncedly the photosynthesis and growth of maize plants than salinity stress. Under alkaline salt stress conditions, metal ions formed massive precipitates, which ultimately reduced plant nutrient availability. On the other hand, high neutral salt stress induced metabolic changes in the direction of gluconeogenesis leading to the enhanced formation of sugars as a reaction contributing to the mitigation of osmotic stress. Thus, the active synthesis of sugars in shoots was essential to the development of salt tolerance. However, the alkaline salt stress conditions characterized by elevated pH values suppressed substantially the levels of photosynthesis, N metabolism, glycolysis, and the production of sugars and amino acids. CONCLUSIONS: These results indicate the presence of different defensive mechanisms responsible for the plant responses to neutral salt and alkaline salt stresses. In addition, the increased concentration of organic acids and enhanced metabolic energy might be potential major factors that can contribute to the maintenance intracellular ion balance in maize plants and counteract the negative effects of high pH under alkaline salt stress.

Comparative metabolic responses and adaptive strategies of wheat (Triticum aestivum) to salt and alkali stress.

BACKGROUND: It is well known that salinization (high-pH) has been considered as a major environmental threat to agricultural systems. The aim of this study was to investigate the differences between salt stress and alkali stress in metabolic profiles and nutrient accumulation of wheat; these parameters were also evaluated to determine the physiological adaptive mechanisms by which wheat tolerates alkali stress. RESULTS: The harmful effect of alkali stress on the growth and photosynthesis of wheat were stronger than those of salt stress. High-pH of alkali stress induced the most of phosphate and metal ions to precipitate; as a result, the availability of nutrients significantly declined. Under alkali stress, Ca sharply increased in roots, however, it decreased under salt stress. In addition, we detected the 75 metabolites that were different among the treatments according to GC-MS analysis, including organic acids, amino acids, sugars/polyols and others. The metabolic data showed salt stress and alkali stress caused different metabolic shifts; alkali stress has a stronger injurious effect on the distribution and accumulation of metabolites than salt stress. These outcomes correspond to specific detrimental effects of a highly pH environment. CONCLUSIONS: Ca had a significant positive correlation with alkali tolerates, and increasing Ca concentration can immediately trigger SOS Na exclusion system and reduce the Na injury. Salt stress caused metabolic shifts toward gluconeogenesis with increased sugars to avoid osmotic stress; energy in roots and active synthesis in leaves were needed by wheat to develop salt tolerance. Alkali stress (at high pH) significantly inhibited photosynthetic rate; thus, sugar production was reduced, N metabolism was limited, amino acid production was reduced, and glycolysis was inhibited.

Dynamic variation of nutrient absorption, metabolomic and transcriptomic indexes of soybean (Glycine max) seedlings under phosphorus deficiency.

The dynamic trajectory of metabolites and gene expression related to phosphorus absorption and utilization in soybean seedling roots were determined under short- and long-term phosphorus deficiency stress. The metabolome results showed that TCA and GS/GOGAT cycles were enhanced after 2 days of phosphorus deficiency stress; however, they were inhibited after 15 days. GC-TOF-MS showed that phosphorus deficiency increased the accumulation of amino acids significantly after 2 days, whereas organic acids and lipid substances increased significantly after 15 days. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed that transcriptional levels of five key genes related to phosphorus activation and phosphorus starvation signal transduction increased continuously with phosphorus deficiency. The expression of GmPHT1 and GmSPX triggered the phosphorus starvation signal pathway and induced the expression of the GmPS and GmPAP genes to enhance the synthesis and secretion of organophosphorus hydrolase and organic acid in soybean roots under phosphorus deficiency. The phospholipid metabolism was enhanced significantly after 15 days of stress and when GmSQD, a crucial enzyme in lipid biosynthesis, was up-regulated. Thus, we propose that future investigations on stress caused by phosphorus deficiency should include more organs obtained at different developmental stages.

Thinning of the Lamina Cribrosa and Deep Layer Microvascular Dropout in Patients With Open Angle Glaucoma and High Myopia.

PRCIS: Lamina cribrosa (LC) thinning (thickness of ≤128.00 µm) helps to distinguish open angle glaucoma from high myopia, which was associated with the presence of microvasculature dropout and elevated intraocular pressure. PURPOSE: The purpose of this study was to analyze the factors associated with LC thickness in highly myopic eyes with and without open angle glaucoma. METHODS: In total, 240 highly myopic eyes with γ-zones (194 eyes without and 46 eyes with open angle glaucoma) were examined, and the LC center, externally oblique border, an abrupt change of scleral curvature (scleral step), deep layer microvasculature dropout and global retinal nerve fiber layer thickness were investigated on optical coherence tomography and optical coherence tomography angiography. RESULTS: LC were thinner in highly myopic open angle glaucoma compared with high myopia alone (107.76±9.86 vs. 137.07±18.51 µm, P <0.001), which was associated with deep layer microvasculature dropout and elevated intraocular pressure. The areas under the receiver operating characteristic curve for detecting open angle glaucoma from the LC thickness was 0.964, which was statistically higher ( P <0.05) than from the global retinal nerve fiber layer thickness (0.921) and vertical cup-to-disc ratio (0.902). A LC thickness cutoff value of 128 µm provided 100% sensitivity for detecting open angle glaucoma with 84% specificity. CONCLUSIONS: Highly myopic eyes with open angle glaucoma appear to have a thinner LC, which was associated with elevated intraocular pressure and deep layer microvasculature dropout. LC thinning (≤128.00 µm) helps distinguish open angle glaucoma from high myopia with an abnormal retinal nerve fiber layer thickness distribution and unclear shallow disc cupping.

Polyhydroxyalkanoates: the natural biopolyester for future medical innovations.

Polyhydroxyalkanoates (PHAs) are a family of natural microbial biopolyesters with the same basic chemical structure and diverse side chain groups. Based on their excellent biodegradability, biocompatibility, thermoplastic properties and diversity, PHAs are highly promising medical biomaterials and elements of medical devices for applications in tissue engineering and drug delivery. However, due to the high cost of biotechnological production, most PHAs have yet to be applied in the clinic and have only been studied at laboratory scale. This review focuses on the biosynthesis, diversity, physical properties, biodegradability and biosafety of PHAs. We also discuss optimization strategies for improved microbial production of commercial PHAs via novel synthetic biology tools. Moreover, we also systematically summarize various medical devices based on PHAs and related design approaches for medical applications, including tissue repair and drug delivery. The main degradation product of PHAs, 3-hydroxybutyrate (3HB), is recognized as a new functional molecule for cancer therapy and immune regulation. Although PHAs still account for only a small percentage of medical polymers, up-and-coming novel medical PHA devices will enter the clinical translation stage in the next few years.

Macroscale Thalamic Functional Organization Disturbances and Underlying Core Cytoarchitecture in Early-Onset Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia is a polygenetic mental disorder with heterogeneous positive and negative symptom constellations, and is associated with abnormal cortical connectivity. The thalamus has a coordinative role in cortical function and is key to the development of the cerebral cortex. Conversely, altered functional organization of the thalamus might relate to overarching cortical disruptions in schizophrenia, anchored in development. STUDY DESIGN: Here, we contrasted resting-state fMRI in 86 antipsychotic-naive first-episode early-onset schizophrenia (EOS) patients and 91 typically developing controls to study whether macroscale thalamic organization is altered in EOS. Employing dimensional reduction techniques on thalamocortical functional connectome (FC), we derived lateral-medial and anterior-posterior thalamic functional axes. STUDY RESULTS: We observed increased segregation of macroscale thalamic functional organization in EOS patients, which was related to altered thalamocortical interactions both in unimodal and transmodal networks. Using an ex vivo approximation of core-matrix cell distribution, we found that core cells particularly underlie the macroscale abnormalities in EOS patients. Moreover, the disruptions were associated with schizophrenia-related gene expression maps. Behavioral and disorder decoding analyses indicated that the macroscale hierarchy disturbances might perturb both perceptual and abstract cognitive functions and contribute to negative syndromes in patients. CONCLUSIONS: These findings provide mechanistic evidence for disrupted thalamocortical system in schizophrenia, suggesting a unitary pathophysiological framework.

The influence of freeway curve characteristics on drivers' speed perception accuracy.

Owing to the complicated geometric conditions and increasingly diversified driving environment, freeway curves have become a road section with frequent serious accidents. To ensure safe driving on curves, drivers must first perceive the movement condition and the vehicle's position, and accurately evaluate the characteristics of the road to make the right speed choice. In this process, the perception of speed plays a crucial role. The present study aims to investigate the driver's speed perception characteristics with respect to freeway curves to better understand the driver speed selection mechanism. We first construct six three-dimensional (3D) virtual highway models, which are consistent with the geometric lines and traffic engineering instruments of real freeways. A virtual simulation test is then conducted in a highly immersive environment. After the completion of the simulation experiment, we conduct a field verification experiment, test the actual driving speed and perceived speed of drivers in the same place as the simulation experiment, and verify the effectiveness of the simulation method. Finally, 25 3D curve models of four different types are constructed, and the influence of curve characteristics (e.g., curve radius, curve combination, tangent length between curves) on drivers' speed perception accuracy are tested on the simulation platform. The results show that the driver's perceived speed is lower than the real speed when driving on curves, and the tangent-to-spiral (TS) point is the section where the driver's speed is most underestimated. Radius was the most important factor affecting driver's speed perception, but the tangent length between curves also had a lesser influence. However, the curve combination had no effect on it. Our findings can help researchers and road designers understand the reasons for drivers' speed choice, thus promoting drivers' safety on freeway curves.

The novel HLA-A*31:191 allele was identified in a Chinese platelet donor.

HLA-A*31:191 differs from HLA-A*31:01:02:01 by one single nucleotide substitution at nucleotide 74.

Investigation of Macular Structural and Microcirculatory Characteristics of Posterior Staphyloma in High Myopic Eyes by Swept Source Optical Coherence Tomography Angiography.

Purpose: To investigate the characteristics of macular structures and microcirculation of posterior staphyloma (PS) and explored factors related to PS in eyes with high myopia. Methods: There were 114 eyes of 82 patients in this study. Using 1:1 matching of the axial length of myopic eyes, patients were divided into no PS (NPS) and PS groups. Comprehensive ophthalmic examinations were performed on all patients. Structural parameters were acquired using swept source optical coherence tomography (SS-OCT). OCT angiography (OCTA) was used to measure the microcirculation parameters. Generalized estimated equation and linear correlation analysis were used for the statistical analysis. Results: Patients with PS had a thinner retinal thickness (RT) and choroid thickness (CT) (all p < 0.05) in the measurement areas and a significantly lower subfoveal scleral thickness (SFST) (p < 0.001) than those without PS. Retinal deep vascular complex density (DVD) (all p < 0.05) and choriocapillaris perfusion area (CCPA) (all p < 0.001) were significantly lower in the measurement areas of the PS group than in those of the NPS group. There was no significant difference in the retinal superficial vascular density between the two groups. Generalized estimating equation indicated that SFST (B = 0.079, p = 0.001), parafoveal RT (B = -0.162, p = 0.041), foveal CT (B = 0.292, p = 0.013), parafoveal CT (B = -0.157, p = 0.023), foveal CCPA (B = 0.691, p = 0.003) and parafoveal CCPA (B = -0.026, p = 0.004) were significantly correlated with PS. Age (r = -0.323, p = 0.001), spherical equivalent refraction (SER) (r = 0.289, p = 0.004), subfoveal CT (r = 0.398, p < 0.001), foveal DVD (r = 0.346, p < 0.001), foveal CT (r = 0.429, p < 0.001), and foveal CCPA (r = 0.387, p < 0.001) were strongly correlated with SFST. Conclusions: The macular structures and microcirculation in the PS group were different from those in the NPS group. SFST, CT, and CCPA were significantly correlated with PS. Lower SFST in PS was correlated with abnormalities of CT and microcirculation.