N123I mutation in the ALV-J receptor-binding domain region enhances viral replication ability by increasing the binding affinity with chNHE1.

The subgroup J avian leukosis virus (ALV-J), a retrovirus, uses its gp85 protein to bind to the receptor, the chicken sodium hydrogen exchanger isoform 1 (chNHE1), facilitating viral invasion. ALV-J is the main epidemic subgroup and shows noteworthy mutations within the receptor-binding domain (RBD) region of gp85, especially in ALV-J layer strains in China. However, the implications of these mutations on viral replication and transmission remain elusive. In this study, the ALV-J layer strain JL08CH3-1 exhibited a more robust replication ability than the prototype strain HPRS103, which is related to variations in the gp85 protein. Notably, the gp85 of JL08CH3-1 demonstrated a heightened binding capacity to chNHE1 compared to HPRS103-gp85 binding. Furthermore, we showed that the specific N123I mutation within gp85 contributed to the enhanced binding capacity of the gp85 protein to chNHE1. Structural analysis indicated that the N123I mutation primarily enhanced the stability of gp85, expanded the interaction interface, and increased the number of hydrogen bonds at the interaction interface to increase the binding capacity between gp85 and chNHE1. We found that the N123I mutation not only improved the viral replication ability of ALV-J but also promoted viral shedding in vivo. These comprehensive data underscore the notion that the N123I mutation increases receptor binding and intensifies viral replication.

OASL suppresses infectious bursal disease virus replication by targeting VP2 for degrading through the autophagy pathway.

Infectious bursal disease (IBD) is an acute and fatal immunosuppressive disease caused by infectious bursal disease virus (IBDV). As an obligate intracellular parasite, IBDV infection is strictly regulated by host factors. Knowledge on the antiviral activity and possible mechanism of host factors might provide the theoretical basis for the prevention and control of IBD. In this study, RNA-sequencing results indicated that many host factors were induced by IBDV infection, among which the expression levels of OASL (2´,5´-oligadenylate synthetase-like protein) was significantly upregulated. OASL overexpression significantly inhibited IBDV replication, whereas OASL knockdown promoted IBDV replication. Interestingly, the antiviral ability of OASL was independent of its canonical enzymatic activity, i.e., OASL targeted viral protein VP2 for degradation, depending on the autophagy receptor p62/SQSTM1 in the autophagy pathway. Additionally, the 316 lysine (K) of VP2 was the key site for autophagy degradation, and its replacement with arginine disrupted VP2 degradation induced by OASL and enhanced IBDV replication. Importantly, our results for the first time indicate a unique and potent defense mechanism of OASL against double-stranded RNA virus by interaction with viral proteins, which leads to their degradation. IMPORTANCE: OASL (2´,5´-oligadenylate synthetase-like protein) exhibits broad-spectrum antiviral effects against single-stranded RNA viruses in mammals, potentially serving as a promising target for novel antiviral strategies. However, its role in inhibiting the replication of double-stranded RNA viruses (dsRNA viruses), such as infectious bursal disease virus (IBDV), in avian species remains unclear. Our findings indicated a unique and potent defense mechanism of OASL against dsRNA viruses. It has been previously shown in mammals that OASL inhibits virus replication through increasing interferon production. The groundbreaking aspect of our study is the finding that OASL has the ability to interact with IBDV viral protein VP2 and target it for degradation and thus exerts its antiviral effect. Our results reveal the interaction between avian natural antiviral immune response and IBDV infection. Our study not only enhances our understanding of bird defenses against viral infections but can also inform strategies for poultry disease management.

Residues E53, L55, H59, and G70 of the cellular receptor protein Tva mediate cell binding and entry of the novel subgroup K avian leukosis virus.

Subgroup K avian leukosis virus (ALV-K) is a novel subgroup of ALV isolated from Chinese native chickens. As for a retrovirus, the interaction between its envelope protein and cellular receptor is a crucial step in ALV-K infection. Tva, a protein previously determined to be associated with vitamin B12/cobalamin uptake, has been identified as the receptor of ALV-K. However, the molecular mechanism underlying the interaction between Tva and the envelope protein of ALV-K remains unclear. In this study, we identified the C-terminal loop of the LDL-A module of Tva as the minimal functional domain that directly interacts with gp85, the surface component of the ALV-K envelope protein. Further point-mutation analysis revealed that E53, L55, H59, and G70, which are exposed on the surface of Tva and are spatially adjacent, are key residues for the binding of Tva and gp85 and facilitate the entry of ALV-K. Homology modeling analysis indicated that the substitution of these four residues did not significantly impact the Tva structure but impaired the interaction between Tva and gp85 of ALV-K. Importantly, the gene-edited DF-1 cell line with precisely substituted E53, L55, H59, and G70 was completely resistant to ALV-K infection and did not affect vitamin B12/cobalamin uptake. Collectively, these findings not only contribute to a better understanding of the mechanism of ALV-K entry into host cells but also provide an ideal gene-editing target for antiviral study.

Associations of MRI-Derived Glymphatic System Impairment With Global White Matter Damage and Cognitive Impairment in Mild Traumatic Brain Injury: A DTI-ALPS Study.

BACKGROUND: Assessing the glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS) may be helpful for mild traumatic brain injury (mTBI) management. PURPOSE: To assess glymphatic function using DTI-ALPS and its associations with global white matter damage and cognitive impairment in mTBI. STUDY TYPE: Prospective. POPULATION: Thirty-four controls (44.1% female, mean age 49.2 years) and 58 mTBI subjects (43.1% female, mean age 48.7 years), including uncomplicated mTBI (N = 32) and complicated mTBI (N = 26). FIELD STRENGTH/SEQUENCE: 3-T, single-shot echo-planar imaging sequence. ASSESSMENT: Magnetic resonance imaging (MRI) was done within 1 month since injury. DTI-ALPS was performed to assess glymphatic function, and peak width of skeletonized mean diffusivity (PSMD) was used to assess global white matter damage. Cognitive tests included Auditory Verbal Learning Test and Digit Span Test (forward and backward). STATISTICAL TESTS: Neuroimaging findings comparisons were done between mTBI and control groups. Partial correlation and multivariable linear regression assessed the associations between DTI-ALPS, PSMD, and cognitive impairment. Mediation effects of PSMD on the relationship between DTI-ALPS and cognitive impairment were explored. P-value <0.05 was considered statistically significant, except for cognitive correlational analyses with a Bonferroni-corrected P-value set at 0.05/3 ≈ 0.017. RESULTS: mTBI showed lower DTI-ALPS and higher PSMD, especially in complicated mTBI. DTI-ALPS was significantly correlated with verbal memory (r = 0.566), attention abilities (r = 0.792), executive function (r = 0.618), and PSMD (r = -0.533). DTI-ALPS was associated with verbal memory (ß = 8.77, 95% confidence interval [CI] 5.00, 12.54), attention abilities (ß = 5.67, 95% CI 4.56, 6.97), executive function (ß = 2.34, 95% CI 1.49, 3.20), and PSMD (ß = -0.79, 95% CI -1.15, -0.43). PSMD mediated 46.29%, 20.46%, and 24.36% of the effects for the relationship between DTI-ALPS and verbal memory, attention abilities, and executive function. DATA CONCLUSION: Glymphatic function may be impaired in mTBI reflected by DTI-ALPS. Glymphatic dysfunction may cause cognitive impairment related to global white matter damage after mTBI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Clear cell renal cell carcinoma with small intestine invasion mimicking intestinal tumor.

A 65-year-old man presented with asymptomatic retroperitoneal mass that had been detected on ultrasonography performed during a physical screening. He had no hematochezia, hematuria or any other symptoms. Tumor markers were normal, including alpha fetoprotein, carcinoembryonic antigen, neuron-specific enolase and cancer antigen 199. Abdominal CT demonstrated a retroperitoneal mass (white arrow) accompanied by significant thickening of the jejunal wall, involving the left kidney. After enhancement, the mass showed rapid enhancement at arterial phase and venous phase, showed washout at delayed phase. Multi-planar reformation revealed the mass involving the pancreatic tail and the left renal pelvis. Surgical resection was performed and pathological examination confirmed clear cell renal cell carcinoma involving pancreas and jejunum, with immunohistochemical results as follows: CK (partly +), Vimentin (partly +), Pax-8 (+), CD10 (+), P505s (partly +), CA-IX (+), TFE-3 (-), Syn (-), CgA (-), CD56 (+), S-100 (-), SOX-10 (-), HMB-45 (-), Desmin (-),CD117 (-), DOG-1 (-), Melan-A (-), SMA (-), CD34 (+), CD31 (+), CD68 (+), Ki67 (5%+). Discussion.

Residues L55 and W69 of Tva Mediate Entry of Subgroup A Avian Leukosis Virus.

The receptor of the subgroup A avian leukosis virus (ALV-A) in chicken is Tva, which is the homologous protein of human CD320 (huCD320), contains a low-density lipoprotein (LDL-A) module and is involved in the uptake of transcobalamin bound vitamin B12/cobalamin (Cbl). To map the functional determinants of Tva responsible for ALV-A receptor activity, a series of chimeric receptors were created by swapping the LDL-A module fragments between huCD320 and Tva. These chimeric receptors were then used for virus entry and binding assays to map the minimal ALV-A functional domain of Tva. The results showed that Tva residues 49 to 71 constituted the minimal functional domain that directly interacted with the ALV-A gp85 protein to mediate ALV-A entry. Single-residue substitution analysis revealed that L55 and W69, which were spatially adjacent on the surface of the Tva structure, were key residues that mediate ALV-A entry. Structural alignment results indicated that L55 and W69 substitutions did not affect the Tva protein structure but abolished the interaction force between Tva and gp85. Furthermore, substituting the corresponding residues of huCD320 with L55 and W69 of Tva converted huCD320 into a functional receptor of ALV-A. Importantly, soluble huCD320 harboring Tva L55 and W69 blocked ALV-A entry. Finally, we constructed a Tva gene-edited cell line with L55R and W69L substitutions that could fully resist ALV-A entry, while Cbl uptake was not affected. Collectively, our findings suggested that amino acids L55 and W69 of Tva were key for mediating virus entry. IMPORTANCE Retroviruses bind to cellular receptors through their envelope proteins, which is a crucial step in infection. While most retroviruses require two receptors for entry, ALV-A requires only one. Various Tva alleles conferring resistance to ALV-A, including Tvar1 (C40W substitution), Tvar2 (frame-shifting four-nucleotide insertion), Tvar3, Tvar4, Tvar5, and Tvar6 (deletion in the first intron), are known. However, the detailed entry mechanism of ALV-A in chickens remains to be explored. We demonstrated that Tva residues L55 and W69 were key for ALV-A entry and were important for correct interaction with ALV-A gp85. Soluble Tva and huCD320 harboring the Tva residues L55 and W69 effectively blocked ALV-A infection. Additionally, we constructed gene-edited cell lines targeting these two amino acids, which completely restricted ALV-A entry without affecting Cbl uptake. These findings contribute to a better understanding of the infection mechanism of ALV-A and provided novel insights into the prevention and control of ALV-A.

TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation.

Infectious bursal disease virus (IBDV), a double-stranded RNA virus, causes immunosuppression and high mortality in 3-6-week-old chickens. Innate immune defense is a physical barrier to restrict viral replication. After viral infection, the host shows crucial defense responses, such as stimulation of antiviral effectors to restrict viral replication. Here, we conducted RNA-seq in avian cells infected by IBDV and identified TRIM25 as a host restriction factor. Specifically, TRIM25 deficiency dramatically increased viral yields, whereas overexpression of TRIM25 significantly inhibited IBDV replication. Immunoprecipitation assays indicated that TRIM25 only interacted with VP3 among all viral proteins, mediating its K27-linked polyubiquitination and subsequent proteasomal degradation. Moreover, the Lys854 residue of VP3 was identified as the key target site for the ubiquitination catalyzed by TRIM25. The ubiquitination site destroyed enhanced the replication ability of IBDV in vitro and in vivo. These findings demonstrated that TRIM25 inhibited IBDV replication by specifically ubiquitinating and degrading the structural protein VP3.

Evolocumab attenuate pericoronary adipose tissue density via reduction of lipoprotein(a) in type 2 diabetes mellitus: a serial follow-up CCTA study.

BACKGROUND: Pericoronary adipose tissue (PCAT) density is a biomarker of vessel inflammation, which is supposed to be increased in patients with type 2 diabetes mellitus (T2DM). However, whether the coronary inflammation revealed by this novel index could be alleviated after evolocumab treatment in T2DM remains unknown. METHODS: From January 2020 to December 2022, consecutive T2DM patients with low-density lipoprotein cholesterol ≥ 70 mg/dL on maximally tolerated statin and taking evolocumab were prospectively included. In addition, patients with T2DM who were taking statin alone were recruited as control group. The eligible patients underwent baseline and follow-up coronary CT angiography with an interval of 48-week. To render patients with evolocumab as comparable to those controls, a propensity-score matching design was used to select the matched pairs with a 1:1 ratio. Obstructive lesion was defined as the extent of coronary artery stenosis ≥ 50%; the numbers inside the brackets were interquartile ranges. RESULTS: A total of 170 T2DM patients with stable chest pain were included [(mean age 64 ± 10.6 [range 40-85] years; 131 men). Among those patients, 85 were in evolocumab group and 85 were in control group. During follow-up, low-density lipoprotein cholesterol (LDL-C) level (2.02 [1.26, 2.78] vs. 3.34 [2.53, 4.14], p < 0.001), and lipoprotein(a) (12.1 [5.6, 21.8] vs. 18.9 [13.2, 27.2], p = 0.002) were reduced after evolocumab treatment. The prevalence of obstructive lesions and high-risk plaque features were significantly decreased (p < 0.05 for all). Furthermore, the calcified plaque volume were significantly increased (188.3 [115.7, 361.0] vs. 129.3 [59.5, 238.3], p = 0.015), while the noncalcified plaque volume and necrotic volume were diminished (107.5 [40.6, 180.6] vs. 125.0 [65.3, 269.7], p = 0.038; 0 [0, 4.7] vs. 0 [0, 13.4], p < 0.001, respectively). In addition, PCAT density of right coronary artery was significantly attenuated in evolocumab group (- 85.0 [- 89.0, - 82.0] vs. - 79.0 [- 83.5, - 74.0], p < 0.001). The change in the calcified plaque volume inversely correlated with achieved LDL-C level (r = - 0.31, p < 0.001) and lipoprotein(a) level (r = - 0.33, p < 0.001). Both the changes of noncalcified plaque volume and necrotic volume were positively correlated with achieved LDL-C level and Lp(a) (p < 0.001 for all). However, the change of PCATRCA density only positively correlated with achieved lipoprotein(a) level (r = 0.51, p < 0.001). Causal mediation analysis revealed Lp(a) level mediated 69.8% (p < 0.001) for the relationship between evolocumab and changes of PCATRCA. CONCLUSIONS: In patients with T2DM, evolocumab is an effective therapy to decrease noncalcified plaque volume necrotic volume, and increase calcified plaque volume. Furthermore, evolocumab could attenuate PCAT density, at least in part, via the reduction of lipoprotein(a).

Prognostic value of coronary CT angiography in heart failure patients with preserved ejection fraction.

OBJECTIVES: To investigate the prognostic value of coronary CT angiography (CCTA) in heart failure patients with preserved ejection fraction (HFpEF). METHODS: Between January 2009 and December 2013, 6497 participants (mean age 63 ± 9.4 [range 32-86] years; 4111 men) who underwent CCTA and echocardiography were prospectively included. Participants were divided into HFpEF group and without HFpEF group. The primary endpoint was major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal myocardial infarction (MI), or hospitalization for heart failure (HF). RESULTS: Among those participants, 3096 were identified with HFpEF and 3401 were without HFpEF. Higher prevalence of coronary atherosclerosis was observed in HFpEF group than those without (78.3% vs. 64.9%, p < 0.001). During a median of 11.0 [IQR: 9.0-12.0] years follow-up, participants with HFpEF exhibit a heightened risk of MACEs in CAD-RADS = 0, 1-2, and ≥ 3 respectively (p < 0.001 for all). In the risk-adjusted hazard analysis among participants with HFpEF, CAD-RADS = 1-2 increased a 2.5-time risk for non-fatal MI (adjusted HR: 2.5, 95% CI: 1.5 to 4.3, p < 0.001), while CAD-RADS ≥ 3 conferred 3.9-fold and 3.1-fold higher risk for cardiovascular mortality (adjusted HR: 3.9, 95% CI: 2.2 to 7.1, p < 0.001) and hospitalization due to HF (adjusted HR: 3.1, 95% CI: 1.9 to 5.3, p < 0.001) with reference to CAD-RADS = 0 respectively. CONCLUSIONS: Coronary artery disease is common in participants with HFpEF and associated with MACEs. Among those participants, the presence of CAD-RADS = 1-2 increased the risk of nonfatal MI, while CAD-RADS ≥ 3 were correlated with cardiovascular mortality and hospitalization due to HF. KEY POINTS: • Higher median of CACS and higher CAD-RADS categories were observed in the HFpEF group than those without (p < 0.001 for both). • Participants with HFpEF exhibit a heightened risk of MACEs in CAD-RADS = 0, 1-2, and ≥ 3 respectively (p < 0.001 for all). • In the risk-adjusted hazard analysis among participants with HFpEF, CAD-RADS =1-2 increased a 2.5-time risk for non-fatal MI (adjusted HR: 2.5, 95% CI: 1.5 to 4.3, p < 0.001) with reference to CAD-RADS = 0 respectively.

The short-term effects of blood donation on the ocular parameters including blood flow of the retina and choroid in healthy people using OCT- angiography.

BACKGROUND: To investigate the short-term effects of blood donation on the morphology and blood flow of the retina and choroid in healthy people using optical coherence tomography angiography (OCTA). METHODS: Twenty-eight healthy blood donors (56 eyes) who participated in the 200 ml voluntary blood donation between March 2, 2021 and January 20, 2022 were included. The best corrected visual acuity (BCVA), systolic (SBP) and diastolic blood pressure (DBP), intraocular pressure (IOP), subfoveal choroid thickness (SFCT), retinal thickness (RT), retinal superficial vascular density (SVD), deep vascular density (DVD) and foveal avascular were a (FAZ) were measured and statistically analysed 10 min before, 30 min and 24 h after the blood donation. RESULTS: The 200 ml blood donation could cause significant IOP reduction at 24 h (P = 0.006), which was negatively correlated with SBP (r = -0.268, P = 0.046), while SBP, DBP, or ocular perfusion pressure were not affected (> 0.05). Moreover, no significant difference existed in the OCT and OCTA indexes, including SFCT, RT, SVD, DVD, and FAZ, before and after the 200 ml blood donation (P > 0.05). The visual acuity was not affected either (P > 0.05). CONCLUSIONS: The 200 ml blood donation was noted to be associated with statistically significant IOP reduction at 24 h, while SBP, DBP, or OPP was not affected. The blood flow of the retina and choroid or the visual acuity did not change significantly after the blood donation. Larger studies with different volumes of blood donation were needed to further analysis the effect of blood donation on ocular parameters.

Plaque progression at coronary CT angiography links non-alcoholic fatty liver disease and cardiovascular events: a prospective single-center study.

OBJECTIVES: The presence of non-alcoholic fatty liver disease (NAFLD) has been associated with major adverse cardiovascular events (MACEs); however, the mechanisms that initiate the risk for MACEs in patients with NAFLD remain unknown. We sought to investigate whether plaque progression (PP), determined by coronary CT angiography (CCTA), moderate the relationship between NAFLD and MACEs. METHODS: A total of 1683 asymptomatic participants (mean age, 63.3 ± 9.4 [range, 38-85] years; 1117 men) who underwent baseline and follow-up CCTA examination were prospectively included in our study. All of the participants were divided into the NAFLD and non-NAFLD groups. PP was determined by follow-up CCTA. The primary endpoint was MACEs, defined as the composite of all-cause death, nonfatal myocardial infarction, and unplanned hospitalization for acute coronary syndrome leading to revascularization. RESULTS: At follow-up CCTA, participants with NAFLD showed higher incidence of PP than those without [33.0% (248/752) vs. 16.6% (155/931), p < 0.001]. Compared with non-NAFLD participants, participants with NAFLD had a lower 9.7-year event-free survival rate (80.9 vs. 66.4%, log-rank p < 0.001). Cox regression analysis revealed NAFLD was significantly associated with MACEs (HR = 1.63, 95% CI: 1.28 to 2.06, p < 0.001) after adjusting for covariables. However, this association was no longer significant after adjustment for PP (HR = 1.10, 95% CI: 0.84 to 1.45, p = 0.496). The mediation analysis revealed that PP had a significant indirect effect (ß = 0.0587, 95% CI: 0.0424 to 0.08, p < 0.001) and mediated 99.8% (p = 0.002) for the relationship between NAFLD and MACEs. CONCLUSIONS: Plaque progression, identified by follow-up CCTA, mediates the relationship between NAFLD and MACEs. KEY POINTS: The incidence of CCTA-identified PP was higher for participants with NAFLD than those without NAFLD (248/752 [33.0%] vs. 155/931 [16.6%], p < 0.001). Participants with NAFLD had a lower 9.7-year event-free survival rate than those without NAFLD (66.4% vs. 80.9%, log-rank p < 0.001). The mediation analysis revealed that PP had a significant indirect effect (ß = 0.0587, 95% CI: 0.0424 to 0.08, p < 0.001) and mediated 99.8% (p = 0.002) for the relationship between NAFLD and MACEs.

Porous boron nitride nanofibers as effective nanofillers for poly(vinyl alcohol) composite hydrogels with excellent self-healing performances.

New composite hydrogels with excellent self-healing properties were prepared by combining poly(vinyl alcohol) (PVA) and boron nitride nanofibers (BNNFs) via a facile one-pot assembly method. One-dimensional porous BNNFs with high aspect ratio, abundant hydroxyl functional groups, especially excellent flexibility which has been first demonstrated in experiments, can act as a decent inorganic nanofillers to effectively improve the mechanical and self-healing properties of PVA hydrogels. Both the tensile and compression performances of hydrogels have been greatly improved by the trace addition of BNNFs (only ∼1.25 wt%). Compared with other BN nanofillers with spherical particles and lamellar morphologies, BNNFs with high aspect ratios and good flexibility play a unique role in the preparation of PVA composite hydrogels with cross-linked three-dimensional polymeric networks. This can be explained by the different topological structures of composite hydrogels formed. The abundant hydroxyl functional groups can form a lot of reversible hydrogen bonds with the molecular chains of PVA, so the as-prepared hydrogels have a high self-healing efficiency. The best healing efficiency of the composite hydrogels with 2.25 wt% BNNFs reaches as high as 97.31% after self-healing for 30 minutes. The good flexibility of BNNFs is beneficial to the movement of the PVA chain, which is beneficial to the self-healing process of composite hydrogels. The outstanding self-healing performance is very important for the application of composite hydrogels in the biomedical field and wearable flexible devices.

A facile visualized solid-phase detection of virus-specific nucleic acid sequences through an upconversion activated linear luminescence recovery process.

The development of portable solid-phase biosensors is of great significance for point-of-care testing (POCT). In this work, we constructed a simple visualized solid-phase biosensor based on luminescence resonance energy transfer (LRET) from upconversion nanoparticles (UCNPs) to gold nanoparticles (AuNPs) for quantitative detection of virus-specific nucleic acid sequences. The detection data showed that there was a linear relationship between the luminescence recovery of UCNPs and the concentrations of the target within the range of 5-100 nM, and the limit of detection (LOD) was 0.326 nM. Additionally, the luminescence recovery of UCNPs was visualized and quantitatively analyzed using a home-built luminescence image capture device and an open-source ImageJ software that can analyze and process images. Compared with conventional liquid-phase biosensors, the solid-phase analysis method we constructed not only has advantages in cost, portability and stability, but also is more conducive to the rapid acquisition and storage of the detected sample, which is expected to become a fast, efficient and reliable detection platform for POCT.

Cognitive impairment in mild traumatic brain injury: a diffusion kurtosis imaging and volumetric study.

BACKGROUND: A significant number of patients with mild traumatic brain injury (mTBI) would experience cognitive deficit. PURPOSE: To investigate the brain structural changes in sub-acute mTBI by diffusion kurtosis imaging (DKI) and volumetric analysis, and to assess the relationship between brain structural changes and cognitive functions. MATERIAL AND METHODS: A total of 23 patients with sub-acute mTBI and 24 control participants were recruited. All the participants underwent examinations of neuropsychological tests, DKI, and magnetic resonance imaging (MRI)-based morphological scans. Images were investigated using whole brain-based analysis and further regions of interest-based analysis for subcortical nuclei. The neuropsychological tests were compared between the mTBI and the control group. Correlation analysis was performed to examine the relationship between gray matter (GM) volume, DKI parameters, and cognitive functions. RESULTS: Compared with control participants, mTBI patients performed worse in the domains of verbal memory, attention and executive function (P < 0.05). No regional GM volume differences were observed between the mTBI and control groups (P > 0.05). Using DKI, patients with mTBI showed lower mean kurtosis (MK) in widespread white matter (WM) regions and several subcortical nuclei (P < 0.05), and higher mean diffusivity (MD) in the right pallidum (P < 0.05). Lower MK value of multiple WM regions and several subcortical nuclei correlated with cognitive impairment (P < 0.05). CONCLUSION: DKI was sensitive in detecting brain microstructural changes in patients with sub-acute mTBI showing lower MK value in widespread WM regions and several subcortical nuclei, which were statistically associated with cognitive deficits.

Daidzein promotes milk synthesis and proliferation of mammary epithelial cells via the estrogen receptor α-dependent NFκB1 activation.

Isoflavones possess a wide range of physiological effects. However, it is still unclear whether isoflavones can promote milk synthesis in mammary gland. This study aimed to determine the effects of a main soy isoflavone, daidzein, on milk synthesis and proliferation of mammary epithelial cells (MECs) and reveal the underlying molecular mechanism. Primary bovine MECs were treated with different concentrations of daidzein (0, 5, 10, 20, 40, and 80 µM). Daidzein dose-dependently promoted α- and ß-casein and lipid synthesis, cell cycle transition, and cell amount, with the best stimulatory effect at 20 µM. Daidzein also stimulated mTOR activation and Cyclin D1 and SREBP-1c expression. Daidzein induced the expression and nuclear localization of estrogen receptor α (ERα), and ERα knockdown blocked the stimulation of daidzein on these above signaling pathways. ERα knockdown also abolished the stimulation of daidzein on NFκB1 expression and phosphorylation, and NFκB1 was required for daidzein to enhance the mTOR, Cyclin D1 and SREBP-1c signaling pathways. In summary, our findings reveal that daidzein stimulates milk synthesis and proliferation of MECs via the ERα-dependent NFκB1 activation.

Coronary CT Angiography in Asymptomatic Adults with Hepatic Steatosis.

Background The long-term prognostic value of coronary CT angiography (CCTA) in asymptomatic adults with hepatic steatosis (HS) remains unknown. Purpose To evaluate the long-term prognostic value of CCTA in asymptomatic adults with HS. Materials and Methods Between January 2009 and December 2013, consecutive asymptomatic adults who underwent CCTA evaluation and unenhanced abdominal CT were prospectively enrolled. All participants were divided into two groups-with HS and without HS according to abdominal CT results. The primary end point was major adverse cardiovascular events (MACEs), defined as cardiac death, stroke, myocardial infarction, and angina requiring hospitalization. Multivariable Cox regression analysis and Kaplan-Meier analysis were used to compare survival rates. Results One thousand thirteen participants with HS and 1940 participants without HS who completed the follow-up were included (mean age, 66 years ± 10 [standard deviation] [range, 29-90 years]; 1940 men). During a median of 7.2 years of follow-up (interquartile range, 6.3-8.1), MACEs were observed in 96 of 1013 participants with HS (10%), whereas 80 of 1940 participants without HS (4%) had MACEs. In participants with a Coronary Artery Disease Reporting and Data System (CAD-RADS) category of 0, both participants with and without HS had a similar 8.8-year event-free survival rate (99.2% event-free survival rate in participants with HS vs 99.0% event-free survival rate in participants without HS, P = .77). As for participants with CAD-RADS categories 1 or 2 or 3-5, the 8.8-year event-free survival rate was lower in participants with HS than in those without HS (70.6% vs 85.2%, P < .001; 51.4% vs 71.7%, P = .03, respectively). The risk of MACEs was higher for participants with HS than for those without HS in CAD-RADS categories 1 and 2 (adjusted hazard ratio = 2.3; 95% CI: 1.4, 3.9; P < .001) and CAD-RADS categories 3-5 (adjusted HR = 2.1; 95% CI: 1.2, 3.6; P = .006) but not in the setting of CAD-RADS category 0 (adjusted HR = 5.1; 95% CI: 0.1, 398; P = .47). Conclusion Asymptomatic participants with hepatic steatosis (HS) had a worse prognosis than those without HS in the presence of coronary artery disease (CAD) at coronary CT angiography, whereas participants with HS and without CAD might have excellent clinical outcomes during a median follow-up of 7.2 years. © RSNA, 2021 Online supplemental material is available for this article.

The Bipartite Sequence Motif in the N and C Termini of gp85 of Subgroup J Avian Leukosis Virus Plays a Crucial Role in Receptor Binding and Viral Entry.

Subgroup J avian leukemia virus (ALV-J), belonging to the genus Alpharetrovirus, enters cells through its envelope surface unit (gp85) via specifically recognizing the cellular receptor chicken Na+/H+ exchanger type I (chNHE1), the 28 to 39 N-terminal residues of which were characterized as the minimal receptor functional domain in our previous studies. In this study, to further clarify the precise organization and properties of the interaction between ALV-J gp85 and chNHE1, we identified the chNHE1-binding domain of ALV-J gp85 using a series of gp85 mutants with segment substitutions and evaluating their effects on chNHE1 binding in protein-cell binding assays. Our results showed that hemagglutinin (HA) substitutions of amino acids (aa) 38 to 131 (N terminus of gp85) and aa 159 to 283 (C terminus of gp85) significantly inhibited the interaction between gp85 and chNHE1/chNHE1 loop 1. In addition, these HA-substituted chimeric gp85 proteins could not effectively block the entry of ALV-J into chNHE1-expressing cells. Furthermore, analysis of various N-linked glycosylation sites and cysteine mutants in gp85 revealed that glycosylation sites (N6 and N11) and cysteines (C3 and C9) were directly involved in receptor-gp85 binding and important for the entry of ALV-J into cells. Taken together, our findings indicated that the bipartite sequence motif, spanning aa 38 to 131 and aa 159 to 283, of ALV-J gp85 was essential for binding to chNHE1, with its two N-linked glycosylation sites and two cysteines being important for its receptor-binding function and subsequent viral infection steps.IMPORTANCE Infection of a cell by retroviruses requires the attachment and fusion of the host and viral membranes. The specific adsorption of envelope (Env) surface proteins to cell receptors is a key step in triggering infections and has been the target of antiviral drug screening. ALV-J is an economically important avian pathogen that belongs to the genus Alpharetrovirus and has a wider host range than other ALV subgroups. Our results showed that the amino acids 38 to 131 of the N terminus and 159 to 283 of the C terminus of ALV-J gp85 controlled the efficiency of gp85 binding to chNHE1 and were critical for viral infection. In addition, the glycosylation sites (N6 and N11) and cysteines (C3 and C9) of gp85 played a crucial role in the receptor binding and viral entry. These findings might help elucidate the mechanism of the entry of ALV-J into host cells and provide antiviral targets for the control of ALV-J.

Development and assessment of the usability of a web-based referral to treatment tool for persons with substance use disorders.

BACKGROUND: Hospitalized people with unhealthy substance use should be referred to treatment. Although inpatient referral resources are often available, clinicians report that outpatient referral networks are not well-established. The purpose of this manuscript is to describe the development and usability testing of a web-based Referral to Treatment Tool (RTT © 2020 Trustees of Indiana University, all rights reserved) designed to identify treatment centers for people with unhealthy substance use. RESULTS: The RTT was conceptualized, developed, and then populated with public use and local survey data of treatment centers from 14 market ZIP codes of hospitals participating in an SBIRT implementation study. The tool underwent initial heuristic testing, followed by usability testing at three hospitals within a large healthcare system in the Midwest region of the United States. Administrative (n = 6) and provider (n = 12) users of the RTT completed a list of tasks and provided feedback through Think-Aloud Tests, the System Usability Scale, and in-person interviews. Patients (n = 4) assessed multiple versions of a take-home printout of referral sites that met their specifications and completed in-person interviews to provide feedback. Each administrative task was completed in less than 3 min, and providers took an average of 4 min and 3 s to identify appropriate referral sites for a patient and print a referral list for the patient. The mean System Usability Scale score (M = 77.22, SD = 15.57, p = 0.03) was significantly higher than the passable score of 70, indicating favorable perceptions of the usability of the RTT. Administrative and provider users felt that the RTT was useful and easy to use, but the settings and search features could be refined. Patients indicated that the printouts contained useful information and that it was helpful to include multiple referral sites on the printout. CONCLUSION: The web-based referral tool has the potential to facilitate voluntary outpatient referral to treatment for patients with unhealthy substance use. The RTT can be customized for a variety of health care settings and patient needs. Additional revisions based on usability testing results are needed to prepare for a broader multi-site clinical evaluation. Trial Registration Not applicable.

Particle Filtering Based Remaining Useful Life Prediction for Electromagnetic Coil Insulation.

Electromagnetic coils are one of the key components of many systems. Their insulation failure can have severe effects on the systems in which coils are used. This paper focuses on insulation degradation monitoring and remaining useful life (RUL) prediction of electromagnetic coils. First, insulation degradation characteristics are extracted from coil high-frequency electrical parameters. Second, health indicator is defined based on insulation degradation characteristics to indicate the health degree of coil insulation. Finally, an insulation degradation model is constructed, and coil insulation RUL prediction is performed by particle filtering. Thermal accelerated degradation experiments are performed to validate the RUL prediction performance. The proposed method presents opportunities for predictive maintenance of systems that incorporate coils.

Facile Electrochemical Method for the Fabrication of Stable Corrosion-Resistant Superhydrophobic Surfaces on Zr-Based Bulk Metallic Glasses.

Both surface microstructure and low surface energy modification play a vital role in the preparation of superhydrophobic surfaces. In this study, a safe and simple electrochemical method was developed to fabricate superhydrophobic surfaces of Zr-based metallic glasses with high corrosion resistance. First, micro-nano composite structures were generated on the surface of Zr-based metallic glasses by electrochemical etching in NaCl solution. Next, stearic acid was used to decrease surface energy. The effects of electrochemical etching time on surface morphology and wettability were also investigated through scanning electron microscopy and contact angle measurements. Furthermore, the influence of micro-nano composite structures and roughness on the wettability of Zr-based metallic glasses was analysed on the basis of the Cassie-Baxter model. The water contact angle of the surface was 154.3° ± 2.2°, and the sliding angle was <5°, indicating good superhydrophobicity. Moreover, the potentiodynamic polarisation test and electrochemical impedance spectroscopy suggested excellent corrosion resistance performance, and the inhibition efficiency of the superhydrophobic surface reached 99.6%. Finally, the prepared superhydrophobic surface revealed excellent temperature-resistant and self-cleaning properties.