Biallelic Cys141Tyr variant of SEL1L is associated with neurodevelopmental disorders, agammaglobulinemia, and premature death.

Suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1L-HRD1) ER-associated degradation (ERAD) plays a critical role in many physiological processes in mice, including immunity, water homeostasis, and energy metabolism; however, its relevance and importance in humans remain unclear, as no disease variant has been identified. Here, we report a biallelic SEL1L variant (p. Cys141Tyr) in 5 patients from a consanguineous Slovakian family. These patients presented with not only ERAD-associated neurodevelopmental disorders with onset in infancy (ENDI) syndromes, but infantile-onset agammaglobulinemia with no mature B cells, resulting in frequent infections and early death. This variant disrupted the formation of a disulfide bond in the luminal fibronectin II domain of SEL1L, largely abolishing the function of the SEL1L-HRD1 ERAD complex in part via proteasomal-mediated self destruction by HRD1. This study reports a disease entity termed ENDI-agammaglobulinemia (ENDI-A) syndrome and establishes an inverse correlation between SEL1L-HRD1 ERAD functionality and disease severity in humans.

Influence of Multi-Frequency Ultrasound Treatment on Conformational Characteristics of Beef Myofibrillar Proteins with Different Degrees of Doneness.

This study evaluated the effect of multi-frequency sonication (20 kHz, 25 kHz, 28 kHz, 40 kHz, 50 kHz) on structural characteristics of beef myofibrillar proteins (MPs) with different degrees of doneness (Rare 52~55 °C, Medium Rare 55~60 °C, Medium 60~65 °C, Medium Well 65~69 °C, Well Down 70~80 °C, and Overcooked 90 °C). The results showed that surface hydrophobicity and sulfhydryl content increased with the increase in degree of doneness. At the same degree of doneness, the sulfhydryl group contents reached the maximum at a frequency of 28 kHz. In addition, the absolute value of ζ-potential was significantly decreased after ultrasonic treatment (p < 0.05). SDS gel electrophoresis showed that the bands of beef MPs were not significantly affected by various ultrasonic frequencies, but the bands became thinner when the degree of doneness reached overcooked. Fourier transform infrared spectrum showed that with the increase of ultrasonic frequency, α-helix content decreased, and random coil content significantly increased (p < 0.05). The results of atomic force microscopy indicated that the surface structure of beef MPs was damaged, and the roughness decreased by sonication, while the roughness significantly increased when the degree of doneness changed from medium to overripe (p < 0.05). In conclusion, multi-ultrasound combined with degree of doneness treatment alters the structural characteristics of beef MPs.

Insights into Ultrasonication Treatment on the Characteristics of Cereal Proteins: Functionality, Conformational and Physicochemical Characteristics.

BACKGROUND: It would be impossible to imagine a country where cereals and their byproducts were not at the peak of foodstuff systems as a source of food, fertilizer, or for fiber and fuel production. Moreover, the production of cereal proteins (CPs) has recently attracted the scientific community's interest due to the increasing demands for physical wellbeing and animal health. However, the nutritional and technological enhancements of CPs are needed to ameliorate their functional and structural properties. Ultrasonic technology is an emerging nonthermal method to change the functionality and conformational characteristics of CPs. Scope and approach: This article briefly discusses the effects of ultrasonication on the characteristics of CPs. The effects of ultrasonication on the solubility, emulsibility, foamability, surface-hydrophobicity, particle-size, conformational-structure, microstructural, enzymatic-hydrolysis, and digestive properties are summarized. CONCLUSIONS: The results demonstrate that ultrasonication could be used to enhance the characteristics of CPs. Proper ultrasonic treatment could improve functionalities such as solubility, emulsibility, and foamability, and is a good method for altering protein structures (including surface hydrophobicity, sulfhydryl and disulfide bonds, particle size, secondary and tertiary structures, and microstructure). In addition, ultrasonic treatment could effectively promote the enzymolytic efficiency of CPs. Furthermore, the in vitro digestibility was enhanced after suitable sonication treatment. Therefore, ultrasonication technology is a useful method to modify cereal protein functionality and structure for the food industry.

Systolic Blood Pressure and 1-Year Clinical Outcomes in Patients Hospitalized for Heart Failure.

Background: High systolic blood pressure (SBP) is an important risk factor for the progression of heart failure (HF); however, the association between SBP and prognosis among patients with established HF was uncertain. This study aimed to investigate the association between SBP and long-term clinical outcomes in patients hospitalized for HF. Methods: This study prospectively enrolled adult patients hospitalized for HF in 52 hospitals from 20 provinces in China. SBPs were measured in a stable condition judged by clinicians during hospitalization before discharge according to the standard research protocol. The primary outcomes included 1-year all-cause death and HF readmission. The multivariable Cox proportional hazards regression models were fitted to examine the association between SBP and clinical outcomes. Restricted cubic splines were used to examine the non-linear associations. Results: The 4,564 patients had a mean age of 65.3 ± 13.5 years and 37.9% were female. The average SBP was 123.2 ± 19.0 mmHg. One-year all-cause death and HF readmission were 16.9 and 32.7%, respectively. After adjustment, patients with SBP < 110 mmHg had a higher risk of all-cause death compared with those with SBP of 130-139 mmHg (HR 1.71; 95% CI: 1.32-2.20). Patients with SBP < 110 mmHg (HR 1.36; 95% CI: 1.14-1.64) and SBP ≥ 150 mmHg (HR 1.26; 95% CI: 1.01-1.58) had a higher risk of HF readmission, and the association between SBP and HF readmission followed a J-curve relationship with the nadir SBP around 130 mmHg. These associations were consistent regardless of age, sex, left ventricular ejection fraction, hypertension, coronary heart disease, and medications for HF. Conclusion: In patients hospitalized for HF, lower SBP in a stable phase during hospitalization portends an increased risk of 1-year death, and a J-curve association has been observed between SBP and 1-year HF readmission. These associations were consistent among clinically important subgroups.

A Robust Lamb Wave Imaging Approach to Plate-Like Structural Health Monitoring of Materials With Transducer Array Position Errors.

The Lamb-wave-based damage imaging via beamforming techniques, which can visualize the location of damage in the structure intuitively, is one of the most promising methods in the field of structural health monitoring (SHM). However, transducer array position errors are inevitable in practical application, which may lead to serious degradation in imaging performance. In this study, it is shown that the uncertainty of the steering vectors led by the imprecise position of transducers in an array can be suppressed by the doubly constrained robust Capon beamformer (DCRCB). After the unwanted side lobes are restrained by the DCRCB-based coherence factor (CF) weighting, an effective adaptive beamforming damage imaging method robust to transducer position errors is proposed. The numerical simulation and imaging experiment of damage on an aluminum plate are carried out to verify the effectiveness of the proposed algorithm. The results show that the proposed Lamb wave damage imaging method performs better than the reported beamforming ones in literature in terms of resolution, contrast, and robustness to transducer position errors.

Investigation of the Solid-Solution Limit, Crystal Structure, and Thermal Quenching Mitigation of Sr-Substituted Rb2CaP2O7:Eu2+ Phosphors for White LED Applications.

Rb2CaP2O7:Eu2+ is a bright reddish-orange-emitting phosphor, but its luminescence thermal stability is poor. In this study, we investigated the solid-solution limit and thermal quenching mitigation of Rb2CaP2O7:Eu2+ phosphors by cation substitution with Sr2+ and revisited their crystal structure. First, we carefully investigated the solid solution limit of Sr in the structure of Rb2CaP2O7. The results show that up to 80% of Ca can be substituted by Sr, whereas Ca hardly resides in the structure of Rb2SrP2O7. Consequently, the photoluminescence was fine-tuned from reddish-orange (612 nm) to yellow (580 nm) light emission by increasing the Sr2+ concentration in the solid-solution phosphors Rb2Sr1-xCaxP2O7:Eu2+ under excitation at 342 nm. The mechanism for the blue shift of the emission spectrum was discussed. With the associated modification of the local environment of the activator (as reflected by the changes in the effective coordination number, average bond length, distortion index, and quadratic elongation), the luminescence thermal quenching issue of Rb2CaP2O7:Eu2+ was mitigated by substituting 20% Sr into the Ca site (Rb2Ca0.8Sr0.2P2O7:Eu2+). The integrated intensity of bright orange-emitting Rb2Ca0.8Sr0.2P2O7:Eu2+ (603 nm) at 150 °C retained 53% of its initial value, 1.64 times that of Rb2CaP2O7:Eu2+ (32.3%). Such an enhancement could be attributed to the improved rigidity of the crystal structure due to the local structure modification as evidenced by Rietveld refinement. The cation substitution is an effective approach for mitigating the thermal quenching issue of phosphors.