Intolerance of uncertainty and negative emotions among high school art students during COVID-19 pandemic: a moderated mediation analysis.

Objectives: A number of high school art students experience negative emotions during their preparation for the art college entrance examination, characterized by worries and fear of uncertainty. Therefore, how individual difference factors, such as intolerance of uncertainty, affect the negative emotions of students needs to be examined. Inspired by the integrative model of uncertainty tolerance, the current study seeks to explain the association between intolerance of uncertainty and negative emotions by testing the potential mediating role of psychological capital and the moderating role of family functioning. Patients and methods: A total of 919 Chinese high school art students (Mage = 18.50 years, range = 16-22) participated from November 2022 to December 2022. Convenience sampling strategies were used. The participants were asked to complete the measures of intolerance of uncertainty scale, psychological capital questionnaire, depression anxiety stress scale, and family adaptability and cohesion evaluation scale. The data were analyzed using Pearson's r correlations and moderated mediation analysis. Results: Results showed that intolerance of uncertainty was positively associated with negative emotions but negatively associated with psychological capital, which in turn, was negatively associated with negative emotions. Psychological capital mediated the indirect link of intolerance of uncertainty with negative emotions. Family functioning buffered the impact of psychological capital on negative emotions. Conclusion: This study can enhance our understanding of the intolerance of uncertainty on negative emotions and provide insights on interventions for high school art students' negative emotions for educators. The interventions targeting intolerance of uncertainty, psychological capital and family functioning may be beneficial in reducing the effect of intolerance of uncertainty on negative emotions faced by high school art students.

MRI T2 mapping and shear wave elastography for identifying main pain generator in delayed-onset muscle soreness: muscle or fascia?

INTRODUCTION: The main generator of delayed onset muscle soreness (DOMS) is still unknown. This study aimed to clarify the main generator of DOMS. METHODS: Twelve participants performed eccentric exercise (EE) on lower legs. MRI and ultrasound were used to assess changes of calf muscle and deep fascia before and after EE. These results were then compared to the muscle pain level. RESULTS: Compared to baseline, muscle pain peaked at 24-48 h after EE (downstairs 22.25 ± 6.196, 57.917 ± 9.298, F = 291.168, p < 0.01; resting 5.833 ± 1.899, 5.083 ± 2.429, F = 51.678, p < 0.01). Shear wave speed (SWE) of the deep fascia and T2 values of the gastrocnemius muscle and deep fascia all increased and peaked at 48 h after EE (1.960 ± 0.130, F = 22.293; 50.237 ± 2.963, F = 73.172; 66.328 ± 2.968, F = 231.719, respectively, p < 0.01). These measurements were positively correlated with DOMS (downstairs: r = 0.46, 0.76, 0.87, respectively, p < 0.001; resting: r = 0.42, 0.70, 0.77, respectively, p < 0.001). There was a significant positive correlation between SWE and T2 values of deep fascia (r = 0.54, p < 0.01). CONCLUSION: DOMS is a common result of muscle and fascia injuries. Deep fascia edema and stiffness play a crucial role in DOMS, which can be effectively evaluated MR-T2 and SWE. CRITICAL RELEVANCE STATEMENT: Delayed-onset muscle soreness is a common result of muscle and deep fascia injuries, in which the edema and stiffness of the deep fascia play a crucial role. Both MRI and shear wave elastography can be effectively used to evaluate soft tissue injuries. KEY POINTS: • The deep fascia is the major pain generator of delayed-onset muscle soreness. • There is a significant correlation between fascia injury and delayed-onset muscle soreness. • MRI and shear wave elastography are preferred methods for assessing fascia injuries.

Clinical Characteristics and Molecular Genetic Analysis of a Pedigree with Glanzmann's Thrombasthenia.

Objective: The objective of this study was to investigate the clinical phenotype and genetic etiology of Glanzmann's thrombasthenia in a consanguineous pedigree. Methods: Clinical data and ancillary test results were collected from pedigrees with Glanzmann's thrombasthenia. High-throughput sequencing was used to detect variants in the proband. Candidate variants were verified by Sanger sequencing. Results: Two patients in the pedigree were homozygous for the c.2248C>T (p. Arg750Ter) variant of the ITGB3 gene. The parents and maternal grandmother, who didn't have any recurrent haemorrhage, were found to carry a heterozygous c.2248C>T variant of the ITGB3 gene, which was absent in the aunt and paternal grandmother. Conclusion: The homozygous variant c.2248C>T (p. Arg750Ter) in the ITGB3 gene underlies the disease in this pedigree. This diagnosis will facilitate genetic counselling in this pedigree for better patient management and life guidance.

AC81 Is a Putative Disulfide Isomerase Involved in Baculoviral Disulfide Bond Formation.

The correct formation of native disulfide bonds is critical for the proper structure and function of many proteins. Cellular disulfide bond formation pathways commonly consist of two parts: sulfhydryl oxidase-mediated oxidation and disulfide isomerase-mediated isomerization. Some large DNA viruses, such as baculoviruses, encode sulfhydryl oxidases, but viral disulfide isomerases have not yet been identified, although G4L in poxvirus has been suggested to serve such a function. Here, we report that the baculovirus core gene ac81 encodes a putative disulfide isomerase. ac81 is conserved in baculoviruses, nudiviruses, and hytrosaviruses. We found that AC81 homologs contain a typical thioredoxin fold conserved in disulfide isomerases. To determine the role of AC81, a series of Autographa californica nucleopolyhedrovirus (AcMNPV) bacmids containing ac81 knockout or point mutations was generated, and the results showed that AC81 is essential for budded virus production, multinucleocapsid occlusion-derived virus (ODV) formation, and ODV embedding in occlusion bodies. Nonreducing Western blot analysis indicated that disulfide bond formation in per os infectivity factor 5 (PIF5), a substrate of the baculoviral sulfhydryl oxidase P33, was abnormal when ac81 was knocked out or mutated. Pulldown assays showed that AC81 interacted with PIF5 and P33 in infected cells. In addition, two critical regions that harbor key amino acids for function were identified in AC81. Taken together, our results suggest that AC81 is a key component involved in the baculovirus disulfide bond formation pathway and likely functions as a disulfide isomerase. IMPORTANCE Many large DNA viruses, such as poxvirus, asfarvirus, and baculovirus, encode their own sulfhydryl oxidase to facilitate the disulfide bond formation of viral proteins. Here, we show that AC81 functions as a putative disulfide isomerase and is involved in multiple functions of the baculovirus life cycle. Interestingly, AC81 and P33 (sulfhydryl oxidase) are conserved in baculoviruses, nudiviruses, and hytrosaviruses, which are all insect-specific large DNA viruses replicating in the nucleus, suggesting that viral disulfide bond formation is an ancient mechanism shared by these viruses.

Serological biomarkers in autoimmune GFAP astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compared to HCs, and 33 of these proteins were not observed in NMOSD patients. Serum levels of EG-VEGF negatively correlated with GFAP antibody titers, MIP-3 alpha positively correlated with clinical severity in GFAP-A patients, and LIGHT positively correlated with WBC counts and protein levels in the CSF of GFAP-A patients. These results suggest that GFAP and AQP4 astrocytopathy share some common pathology related to TNF signaling. Serum MIP 3 alpha may be a biomarker to assess clinical severity and a potential target for therapy of autoimmune GFAP astrocytopathy.

PPARγ Dysfunction in the Medial Prefrontal Cortex Mediates High-Fat Diet-Induced Depression.

Epidemiological studies suggest a bidirectional association between depression and obesity; however, the biological mechanisms that link the development of depression to a metabolic disorder remain unclear. Even though nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) agonists show anti-depressive effect, and high-fat diet-(HFD)-induced PPARγ dysfunction is involved in the pathogenesis of metabolic disorders, the neuronal PPARγ has never been studied in HFD-induced depression. Thus, we aimed to investigate the effect of neuronal PPARγ on depressive-like behaviors in HFD-induced obese mice.We fed male C57BL/6 J mice with HFD to generate obese mice and conducted a series of behavioral tests to assess the effects of HFD feeding on depression. We generated neuron-specific PPARγ knockout mice (NKO) to determine whether neuronal PPARγ deficiency was correlated with depressive-like behaviors. To further prove whether PPARγ in the medial prefrontal cortex (mPFC) neurons is involved in depressive-like behaviors, we applied AAV- CaMKIIα-Cre approach to specifically knockout PPARγ in the mPFC neurons of LoxP mice and used AAV-syn-PPARγ vectors to overexpress PPARγ in the mPFC neurons of NKO mice.We observed a low mPFC PPARγ level and an increase in depressive-like behaviors in the HFD-fed mice. Moreover, neuronal-specific PPARγ deficiency in mice induced depressive-like behaviors, which could be abolished by imipramine. Furthermore, overexpressing PPARγ in the mPFC reversed the depressive-like behaviors in HFD-fed mice as well as in neuronal-specific PPARγ knockout mice.These results implicate that dysregulation of neuronal PPARγ in the mPFC may contribute to an increased risk for depression in obese populations.

Serum molecular biomarkers in neuromyelitis optica and multiple sclerosis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory demyelinating disorder of the central nervous system (CNS), which mainly affects the optic nerves and spinal cord. The aims of this study were to determine whether the expression levels of serological cytokines could distinguish 1) NMOSD from healthy controls (HCs); and 2) NMOSD patients with and without the aquaporin-4 (AQP4) antibody biomarker from each other; and 3) NMOSD patients without the antibody to AQP4 from MS patients. METHODS: The expression levels of 200 proteins in serum from 41 NMOSD (32 with antibodies to AQP4, 9 without antibodies to AQP4), 12 MS patients, and 34 HCs were measured using glass-based antibody arrays. None of the patients received any immunosuppressive treatment. In parallel, the correlation between protein expression in NMOSD/MS patients and clinical traits was determined with Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Thirty-nine serological proteins were differentially expressed in NMOSD patients compared to HCs, with 29 of these proteins not observed in MS patients. In addition, the data reveal 15 differentially-expression proteins (DEPs) between AQP4-IgG seronegative and AQP4-IgG seropositive NMOSD patients, and 9 DEPs between NMOSD and MS patients who did not have AQP4-IgG. CONCLUSION: Serological IL-17B is significantly upregulated in both NMOSD and MS patients compared to HCs, and could be a key biomarker of NMOSD and MS. Serological VEGF, MPIF-1 and NrCAM were positively associated with AQP4-IgG titer. We also demonstrate that EGF may be involved in the breakdown of the BBB by downregulating Claudin-5.

Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress.

Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Both the BIR-like pathway and ICL repair share almost identical molecular mechanisms of 53BP1-BRCA1-controlled signaling response, SLX4- and FAN1-mediated fork cleavage and POLD3-dependent DNA synthesis, suggesting that the FA pathway is intrinsically one of the BIR-like pathways. Replication stress not only triggers BMF in FA-deficient mice, but also specifically induces monosomy 7, which is associated with progression to AML in patients with FA, in FA-deficient cells.

CD8+ T-cell predominance in autoimmune glial fibrillary acidic protein astrocytopathy.

BACKGROUND AND OBJECTIVE: We aimed to report the pathological features of T lymphocytes in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A). METHODS: A retrospective pathological analysis of patients with GFAP-A was performed. RESULTS: Eight patients with GFAP-immunoglobulin G (IgG) and pathological data were included. Their biopsy findings were similar, and all showed marked lymphocytic infiltration in the white matter, with perivascular predominance. The lymphocytic infiltration was predominantly composed of CD8+ T lymphocytes rather than CD4+ T lymphocytes, except in one patient who had overlapping positive myelin oligodendrocyte glycoprotein-IgG. Unlike CD4+ T cells, CD8+ T cells were frequently observed adjacent to dystrophic neurons and astrocytes. There was also diffuse infiltration by CD68+ and CD163+ macrophages. CD8+ astrocytes were identified in two samples, but no CD4+ astrocytes were observed. CONCLUSIONS: A predominance of CD8+ T cells may be an important pathological and diagnostic feature in GFAP-A.

LncRNA H19 Overexpression Activates Wnt Signaling to Maintain the Hair Follicle Regeneration Potential of Dermal Papilla Cells.

Androgenetic alopecia (AGA) is a common hair loss disorder resulting in seriously abnormal social interaction and psychological disorders. Transplantation with autologous dermal papilla cells represents a prospective therapy. However, the ability of dermal papilla cells to induce hair follicle development is lost upon cell culturing. Long non-coding RNAs (lncRNAs) are an important class of genes involved in various biological functions, are aberrantly expressed in disease and may play roles in the regulation of Wnt signaling, a critical pathway in maintaining the hair follicle-inducing capability of dermal papilla cells. Examination of dermal papilla cells by lncRNA microarray revealed that H19 was highly expressed in early passage dermal papilla cells compared with late-passage dermal papilla cells. In this study, we constructed H19-overexpressing dermal papilla cells to examine the role of H19 on hair follicle inductivity. Dermal papilla cells infected with lentivirus encoding H19 maintained their cell shape, and continued to display both multiple-layer aggregation and hair follicle-inducing ability upon prolonged culture. H19 exerted these effects through inducing miR-29a to activate Wnt signaling by directly downregulating the expression of Wnt suppressors, including DKK1, Kremen2, and sFRP2, thereby forming a novel regulatory feedback loop between H19 and miR-29a to maintain hair follicle- inducing potential. These results suggest that lncRNA H19 maintains the hair follicle-inducing ability of dermal papilla cells through activation of the Wnt pathway and could be a target for treatment of androgenetic alopecia.

Highly Stable Reduced Graphene Oxide Wrapped Black Phosphorus Heterostructure with Superior Photocatalytic Performance under Visible Light.

Metal-free photocatalysts with excellent visible-light absorption and highly efficient photocatalytic activity are attractive in the field of photocatalysis owing to their environmental friendliness. Black phosphorus (BP) shows a great potential in photoelectric conversion and photocatalysis due to its tunable band gap and two-dimensional structure. In this work, a stabilized metal-free photocatalyst, reduced graphene oxide (rGO)-wrapped BP heterostructure, was prepared by assembling BP and GO nanosheets in aqueous solution followed by partial reduction and lyophilization. The surface tension of the partially reduced GO during lyophilization could make rGO nanosheets tightly wrap on both surfaces of exfoliated BP nanosheets. This wrapped heterostructure with tight bonding between rGO and BP nanosheets led to a high photocatalytic activity, owing to the rapid transfer of the photogenerated electron-hole pairs at the rGO/BP heterojunction and the high stability of rGO protecting BP from oxygen attack. This work not only provided a general method to prepare the sandwiched heterojunction based on GO with good interface binding capability but also constructed a highly active, stable, metal-free photocatalyst based on BP.

MRI Quantitative Analysis of Eccentric Exercise-induced Skeletal Muscle Injury in Rats.

BACKGROUND: The aim of this study was to investigate the value of magnetic resonance (MR) quantitative analysis (MR-T2 mapping technique) for the evaluation of eccentric exercise-induced skeletal muscle injury. MATERIALS AND METHODS: We established an animal model of eccentric exercise-induced damage of Sprague Dawley rat skeletal muscle and evaluated the animals by MR imaging, determined the serum levels of fast skeletal troponin (fsTnI), and examined muscle histopathology, at 0, 1, 2, 4, and 7 days after eccentric exercise. The associations between MR imaging findings, and histopathological and laboratory results were evaluated. RESULTS: T2-weighted images (WIs) of quadriceps femoris muscles showed obvious high signal intensities after exercise, and the T2 values and serum fsTnI levels continued to increase, peaking at day 2 after exercise, p< 0.05. The histopathological findings in muscle specimens, which included swollen and ruptured cells, enlarged extracellular spaces, inflammation, and regeneration of muscle fibers, showed similar trends. After day 2, muscle specimens began to show evidence of self-repair, the T2WI signals decreased in intensity, and the T2 values and serum fsTnI levels decreased; however, at day 7 post injury, the values remained slightly higher than those in the control animals, p< 0.05. The T2 value was significantly correlated with the serum fsTnI level (r = 0.896, p< 0.01). CONCLUSION: T2 mapping technology accurately reflects the histopathological and fsTnI abnormalities and the degree of skeletal muscle damage associated with eccentric exercise followed by recovery. Because T2 mapping technology is noninvasive and can be quantitatively analyzed, it might become the preferred method for performing the diagnosis of eccentric exercise-induced skeletal muscle injury.

High-fat Diet Mediates Anxiolytic-like Behaviors in a Time-dependent Manner Through the Regulation of SIRT1 in the Brain.

The consumption of a high-fat diet (HFD) and obesity have been associated not only with metabolic diseases but also with neuropsychiatric diseases, such as depression and anxiety. However, results on the effects of an HFD on anxiety are controversial, since both anxiogenic and anxiolytic effects have been reported. In this study, we evaluated the effects of both short- and long-term intake of an HFD on anxiety-like behaviors. To explore the impact of time on the association between an HFD and anxiety, mice were fed with an HFD for 4 weeks or 12 weeks. Compared with control-diet mice, mice given an HFD for 4 weeks displayed anxiolytic-like behaviors. At the same time, we observed decreased SIRT1 expression in the mPFC and the amygdala of HFD-fed mice. Moreover, resveratrol, an activator of SIRT1, reversed the anxiolytic-like behaviors in HFD-fed mice. However, after 12 weeks of consuming a high-fat diet, mice did not exhibit any anti-anxiety behavior or further decreases in SIRT1 expression in the aforementioned brain regions compared with CD-fed mice. When EX-527, a SIRT1 inhibitor, was intraperitoneally injected, we observed anxiolytic effects in the CD-fed mice but not in the 12-week HFD-fed mice. Collectively, our data demonstrate that exposure to a short-term HFD can induce anxiolytic behaviors, which may be associated with decreased SIRT1 in the mPFC and the amygdala. However, this effect is abolished when the high-fat diet is extended to 12 weeks. Together, these results demonstrate that SIRT1 plays an essential role in regulating mood-related behaviors in HFD-fed mice.

miR-124 and miR-9 mediated downregulation of HDAC5 promotes neurite development through activating MEF2C-GPM6A pathway.

The class IIa histone deacetylases (HDACs) play important roles in the central nervous system during diverse biological processes such as synaptic plasticity, axon regeneration, cell apoptosis, and neural differentiation. Although it is known that HDAC5 regulates neuronal differentiation, neither the physiological function nor the regulation of HDAC5 in neuronal differentiation is clear. Here, we identify HDAC5 as an inhibitor of neurite elongation and show that HDAC5 is regulated by the brain enriched microRNA miR-124 and miR-9. We discover that HDAC5 inhibits neurite extension both in differentiated P19 cells and primary neurons. We also show that the neuronal membrane glycoprotein GPM6A (M6a) is a direct target gene of HDAC5 regulated transcriptional factor MEF2C. HDAC5 inhibits neurite elongation, acting at least partially via a MEF2C/M6a signaling pathway. We also confirmed the miR-124/miR-9 regulated HDAC5-MEF2C-M6a pathway regulates neurite development in primary neurons. Thus, HDAC5 emerges as a cellular conductor of MEF2C and M6a activity and is regulated by miR-124 and miR-9 to control neurite development.

miR-124 represses ROCK1 expression to promote neurite elongation through activation of the PI3K/Akt signal pathway.

Recent studies have demonstrated an important role for miR-124, the most abundant and well-conserved brain-specific microRNA(miRNA), in promoting neurite outgrowth and elongation during neuronal differentiation. This miRNA's target genes and the mechanisms that execute this role remain unclear. In this study, we identified ROCK1, a small GTPase Rho kinase, as a direct target of miR-124 for regulating neurite elongation. miR-124 significantly inhibited ROCK1 expression in M17 cells. Inhibiting ROCK1 promoted neurite elongation, and the overexpression of ROCK1 strongly repressed the neurite elongation-enhancing effect of miR-124 in M17 cells. We determined that Akt functions as a novel ROCK1 downstream effector in regulating neurite outgrowth and elongation.