Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque.

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses.

Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5' end sequences derived from cap-snatching in influenza virus mRNA. Here, we report cryo-EM structures to characterize THOV polymerase RNA synthesis initiation and elongation. The structures demonstrate that THOV RNA transcription and replication are able to start with short dinucleotide primers and that the polymerase cap-snatching machinery is likely non-functional. Triggered by RNA synthesis, asymmetric THOV polymerase dimers can form without the involvement of host factors. We confirm that, distinctive from influenza viruses, THOV-polymerase RNA synthesis is weakly dependent of the host factors ANP32A/B/E in human cells. This study demonstrates varied mechanisms in RNA synthesis and host factor utilization among orthomyxoviruses, providing insights into the mechanisms behind thogotoviruses' broad-infectivity range.

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.

Overexpression of TaMPK3 enhances freezing tolerance by increasing the expression of ICE-CBF-COR related genes in the Arabidopsis thaliana.

Mitogen-activated protein kinases (MAPKs) play important roles in plant stress response. As a major member of the MAPK family, MPK3 has been reported to participate in the regulation of chilling stress. However, the regulatory function of wheat (Triticum aestivum ) mitogen-activated protein kinase TaMPK3 in freezing tolerance remains unknown. Dongnongdongmai No.1 (Dn1) is a winter wheat variety with strong freezing tolerance; therefore, it is important to explore the mechanisms underlying this tolerance. In this study, the expression of TaMPK3 in Dn1 was detected under low temperature and hormone treatment. Gene cloning, bioinformatics and subcellular localisation analyses of TaMPK3 in Dn1 were performed. Overexpressed TaMPK3 in Arabidopsis thaliana was obtained, and freezing tolerance phenotype observations, physiological indices and expression levels of ICE-C-repeat binding factor (CBF)-COR -related genes were determined. In addition, the interaction between TaMPK3 and TaICE41 proteins was detected. We found that TaMPK3 expression responds to low temperatures and hormones, and the TaMPK3 protein is localised in the cytoplasm and nucleus. Overexpression of TaMPK3 in Arabidopsis significantly improves freezing tolerance. TaMPK3 interacts with the TaICE41 protein. In conclusion, TaMPK3 is involved in regulating the ICE-CBF-COR cold resistance module through its interaction with TaICE41, thereby improving freezing tolerance in Dn1 wheat.

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.

Avian ANP32A incorporated in avian influenza A virions promotes interspecies transmission by priming early viral replication in mammals.

Species-specific differences in acidic nuclear phosphoprotein 32 family member A (ANP32A) determine the restriction of avian-signature polymerase in mammalian cells. Mutations that evade this restriction, such as PB2-E627K, are frequently acquired when avian influenza A viruses jump from avian hosts to mammalian hosts. However, the mechanism underlying this adaptation process is still unclear. Here, we report that host factor ANP32 proteins can be incorporated into influenza viral particles through combination with the viral RNA polymerase (vPol) and then transferred into targeted cells where they support virus replication. The packaging of the ANP32 proteins into influenza viruses is dependent on their affinity with the vPol. Avian ANP32A (avANP32A) delivered by avian influenza A virions primes early viral replication in mammalian cells, thereby favoring the downstream interspecies transmission event by increasing the total amount of virus carrying adaptive mutations. Our study clarifies one role of avANP32A where it is used by avian influenza virus to help counteract the restriction barrier in mammals.

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.

Iterative Reconstruction Algorithms in Magneto-Acousto-Electrical Computed Tomography (MAE-CT) for Image Quality Improvement.

Magneto-acousto-electrical computed tomography (MAE-CT) is a recently developed rotational magneto-acousto-electrical tomography (MAET) method, which can map the conductivity parameter of tissues with high spatial resolution. Since the imaging mode of MAE-CT is similar to that of CT, the reconstruction algorithms for CT are possible to be adopted for MAE-CT. Previous studies have demonstrated that the filtered back-projection (FBP) algorithm, which is one of the most common CT reconstruction algorithms, can be used for MAE-CT reconstruction. However, FBP has some inherent shortcomings of being sensitive to noise and non-uniform distribution of views. In this study, we introduced iterative reconstruction (IR) method in MAE-CT reconstruction and compared its performance with that of the FBP. The numerical simulation, the phantom, and in vitro experiments were performed, and several IR algorithms (ART, SART, SIRT) were used for reconstruction. The results show that the images reconstructed by the FBP and IR are similar when the data is noise-free in the simulation. As the noise level increases, the images reconstructed by SART and SIRT are more robust to the noise than FBP. In the phantom experiment, noise and some stripe artifacts caused by the FBP are removed by SART and SIRT algorithms. In conclusion, the IR method used in CT is applicable in MAE-CT, and it performs better than FBP, which indicates that the state-of-the-art achievements in the CT algorithm can also be adopted for the MAE-CT reconstruction in the future.

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.

The SUMO-interacting motif in NS2 promotes adaptation of avian influenza virus to mammals.

Species differences in the host factor ANP32A/B result in the restriction of avian influenza virus polymerase (vPol) in mammalian cells. Efficient replication of avian influenza viruses in mammalian cells often requires adaptive mutations, such as PB2-E627K, to enable the virus to use mammalian ANP32A/B. However, the molecular basis for the productive replication of avian influenza viruses without prior adaptation in mammals remains poorly understood. We show that avian influenza virus NS2 protein help to overcome mammalian ANP32A/B-mediated restriction to avian vPol activity by promoting avian vRNP assembly and enhancing mammalian ANP32A/B-vRNP interactions. A conserved SUMO-interacting motif (SIM) in NS2 is required for its avian polymerase-enhancing properties. We also demonstrate that disrupting SIM integrity in NS2 impairs avian influenza virus replication and pathogenicity in mammalian hosts, but not in avian hosts. Our results identify NS2 as a cofactor in the adaptation process of avian influenza virus to mammals.

Smartphone conducted DNA portable quantitative detection platform based on photonic crystals chip and magnetic nanoparticles.

It is of great significance to develop a highly sensitive and intuitive virus detection tool. A portable platform is constructed for quantitative detection of viral DNA based on the principle of fluorescence resonance energy transfer (FRET) between upconversion nanoparticles (UCNPs) and graphene oxide nanosheets (GOs) in this work. To implement a high sensitivity and low detection limit, GOs are modified by magnetic nanoparticles to prepare magnetic graphene oxide nanosheets (MGOs). Among them, the application of MGOs can not only eliminate the background interference, but also amplify the fluorescence intensity to a certain extent. Whereafter, a simple carrier chip based on photonic crystals (PCs) is introduced to realize a visual solid-phase detection, which also amplifies the luminescence intensity of the detection system. Finally, under the application of the 3D printed accessory and smartphone program of red-green-blue (RGB) evaluation, the portable detection can be completed simply and accurately. In a word, this work proposes a portable DNA biosensor with the triple functions of quantification, visualization and real-time detection can be used as a high-quality viral detection strategy and clinical diagnosis method.

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.

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).

JA-induced TaMPK6 enhanced the freeze tolerance of Arabidopsis thaliana through regulation of ICE-CBF-COR module and antioxidant enzyme system.

Mitogen-activated protein kinases (MAPKs) play important roles in the stress response of plants. However, the function of MPK proteins in freeze-resistance in wheat remains unclear. Dongnongdongmai No.1 (Dn1) is a winter wheat variety with a strong freezing resistance at extremely low temperature. In this study, we demonstrated that TaMPK6 is induced by JA signaling and is involved in the modulation of Dn1 freeze resistance. Overexpression of TaMPK6 in Arabidopsis increased the survival rate of plant at -10 â„ƒ. The scavenging ability of reactive oxygen species (ROS) and the expression of cold-responsive genes CBFs and CORs were significantly enhanced in TaMPK6-overexpressed Arabidopsis, suggesting a role of TaMPK6 in activating the ICE-CBF-COR module and antioxidant enzyme system to resist freezing stress. Furthermore, TaMPK6 is localized in the nucleus and TaMPK6 interacts with TaICE41, TaCBF14, and TaMYC2 proteins, the key components in JA signaling and the ICE-CBF-COR pathway. These results suggest that JA-induced TaMPK6 may regulate freezing-resistance in wheat by interacting with the TaICE41, TaCBF14, and TaMYC2 proteins, which in turn enhances the ICE-CBF-COR pathway. Our study revealed the molecular mechanism of TaMPK6 involvement in the cold resistance pathway in winter wheat under cold stress, which provides a basis for enriching the theory of wheat cold resistance.

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.

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.

Improved Magneto-Acousto-Electrical Computed Tomography (MAE-CT) With Multi-Angle Plane Wave Excitation.

As a tissue conductivity imaging method, magneto-acousto-electric tomography (MAET) has the advantage of high axial spatial resolution compared with traditional electrical impedance imaging methods. However, it has the problems of difficulty in imaging targets with irregular conductivity distribution and poor lateral spatial resolution. Although the rotation-based MAET method can partly solve the irregular target problem, there is still a poor imaging signal-to-noise ratio (SNR) problem. Our previous study established a framework of an innovative MAET method, which has a very similar imaging theory and reconstruction algorithm to those of computed tomography (CT). Therefore, we name the method magneto-acoustic-electric computed tomography (MAE-CT). This paper proposes an improved implementation of MAE-CT based on multi-angle plane wave excitation. This method combines the electronic steering of the linear array transducer with the mechanical rotation to increase the number of projection angles while keeping the imaging complexity. In this study, we first established a finite element simulation model to verify the method's feasibility. Then phantom experiments were conducted to systematically investigate the performance of the proposed method. Finally, in vitro liver tissue experiment was conducted to further explore the feasibility of the method. The experimental results show that our method improves both the SNR and spatial resolution of the reconstructed image. For the phantom results, this method can detect conductivity of 0.67 S/m in an area with a size of 2 mm. To the best of our knowledge, this is the best result of spatial resolution available for MAET.

Overexpression of TaMYC2 confers freeze tolerance by ICE-CBF-COR module in Arabidopsis thaliana.

Dongnongdongmai No.1 (Dn1) is one of the few winter wheat varieties that can successfully overwinter at temperatures as low as -25°C or even lower. To date, few researches were carried to identify the freeze tolerance genes in Dn1 and applied them to improve plant resistance to extreme low temperatures. The basic helix-loop-helix (bHLH) transcription factor MYC2 is a master regulator in JA signaling, which has been reported to involve in responses to mild cold stress (2°C and 7°C). We hypothesized that MYC2 might be part of the regulatory network responsible for the tolerance of Dn1 to extreme freezing temperatures. In this study, we showed that wheat MYC2 (TaMYC2) was induced under both extreme low temperature (-10°C and-25°C) and JA treatments. The ICE-CBF-COR transcriptional cascade, an evolutionary conserved cold resistance pathway downstream of MYC2, was also activated in extreme low temperatures. We further showed that overexpression of any of the MYC2 genes from Dn1 TaMYC2A, B, D in Arabidopsis led to enhanced freeze tolerance. The TaMYC2 overexpression lines had less electrolyte leakage and lower malondialdehyde (MDA) content, and an increase in proline content, an increases antioxidant defences, and the enhanced expression of ICE-CBF-COR module under the freezing temperature. We further verified that TaMYC2 might function through physical interaction with TaICE41 and TaJAZ7, and that TaJAZ7 physically interacts with TaICE41. These results elucidate the molecular mechanism by which TaMYC2 regulates cold tolerance and lay the foundation for future studies to improve cold tolerance in plants.

Role of collateral flow in infarct border zone extent and contractile function in patients with chronic coronary total occlusion.

PURPOSE: There is a paucity of data regarding the border zone parameters in patients with chronic coronary total occlusion (CTO). We investigated the border zone extent and contractile function and their associations with collateral flow. METHODS: CTO patients (n = 47) and sex- and age-matched volunteers (n = 15) were prospectively enrolled and underwent cardiac MRI examinations to acquire cine and late-gadolinium enhancement (LGE) images. Myocardial peak strain (PS) and the time to PS were determined at the segmental level and global level. Infarct, border zone, adjacent, and remote regions were defined according to the transmural extent of infarction (TEI) by LGE at each segment. Angiographic collateral flow was evaluated using the Rentrop grading system. RESULTS: CTO patients with well-developed collateral flow had a higher TEI in border zone regions compared to patients with poorly developed collateral flow (p = 0.02). Conversely, CTO patients with poorly developed collaterals showed a higher TEI in infarct regions (p < 0.01). Enhanced border function, characterized by greater PS and earlier time to PS, was noted in well-developed collaterals (all p < 0.05). In the multivariate linear analyses, the level of collateral flow was an independent predictor of the border zone extent (ß = 0.40, p = 0.02) and contractile function (radial: ß = -0.42, p = 0.02; circumferential: ß = 0.39, p = 0.02; and longitudinal: ß = 0.47, p < 0.01). CONCLUSIONS: In CTO patients, the presence of well-developed collateral flow was closely linked to a greater extent of LGE and contractile function in border zone regions. Our findings shed light on the cardiac MRI-based pathophysiological underpinning in border zone regions, which could offer complementary and prognostic information in clinical practice.

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.