Clinical features of retinal amyloid angiopathy with transthyretin Gly83Arg variant.

AIM: To report on the clinical features of patients with retinal amyloid angiopathy (RAA) who were identified to be caused by the transthyretin (TTR) Gly83Arg variant. METHODS: Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021. The clinical features, therapeutic strategies, and prognoses of all patients were reviewed. RESULTS: Five patients with a mean age of 52.00±7.23y were diagnosed as RAA. These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant. Vitreous opacity was found in all 10 eyes, and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis. The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes (29%), neovascular glaucoma in 2 eyes (29%), and iris neovascularization in 1 eye (14%). Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography (FFA) in this group of cases, and the incidence of the retinal non-perfusion area was 67%. Although no cases of retinal neovascularization were found, the prognosis of visual acuity was not ideal. CONCLUSION: This is the first report of RAA in patients with the TTR Gly83Arg variant. Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients. Thereafter, regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential. And FFA after vitrectomy is very important, which can help ophthalmologists detect RAA earlier and treat it in time.

Fatigue Reliability Analysis Method of Reactor Structure Considering Cumulative Effect of Irradiation.

The influence of irradiation should be considered in fatigue reliability analyses of reactor structures under irradiation conditions. In this study, the effects of irradiation hardening and irradiation embrittlement on fatigue performance parameters were quantified and a fatigue life prediction model was developed. Based on this model, which takes into account the cumulative effect of a neutron dose, the total fatigue damage was calculated according to Miner's linear cumulative damage law, and the reliability analysis was carried out using the Monte Carlo simulation method. The case results show that the fatigue life acquired by taking into account the cumulative effect of irradiation was reduced by 24.3% compared with that acquired without considering the irradiation effect. Irradiation led to the increase of the fatigue life at low strains and its decrease at high strains, which is in accordance with the findings of an irradiation fatigue test. The rate of increase in the fatigue life decreased gradually with the increase of the neutron dose. The irradiation performance parameters had a small influence on fatigue reliability, while the fatigue strength coefficient and the elastic modulus had a great influence on the fatigue reliability. Compared with the current method, which uses a high safety factor to determine design parameters, a fatigue reliability analysis method taking into account the cumulative effect of irradiation could be more accurate in the reliability analysis and life prediction of reactor structures.

Investigations on system integration method and dynamic performance of electromechanical actuator.

A highly integrated electromechanical actuator was developed in this article, which aims at fulfilling the requirements of high power-to-weight ratio, high efficiency, high integration and low volume in military equipment. Three different transmission schemes were proposed for the integrated electromechanical actuator according to the differences in integration methods. Comparative analysis was conducted on the specific structures of the integrated electromechanical actuator and the categories and performance of the planetary roller screw, which is the key unit of the integrated electromechanical actuator. An integrated electromechanical actuator was designed based on the project requirements. A mathematical model was established and the system transfer function was derived. Based on this, a simulation model of the position loop system was established using the AMESim software and the effects of some related parameters, such as friction, backlash and stiffness, on the dynamic performance of the system were investigated. The related theory and simulation results were experimentally validated by a self-developed integrated electromechanical actuator research prototype combined with the related test system. The data obtained from the step response tests, sinusoidal response tests and repeat locating accuracy tests indicated that the developed integrated electromechanical actuator prototype is of rapid, accurate and stable position tracking capability.

Maternal exposure to Di-(2-ethylhexyl) phthalate (DEHP) activates the PI3K/Akt/mTOR signaling pathway in F1 and F2 generation adult mouse testis.

Di-(2-ethylhexyl) phthalate (diethylhexyl phthalate, DEHP) can cause male reproductive damage in rodents and human. Moreover, DEHP is known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. The PI3K/Akt/mTOR signaling pathway has been implicated in germ cell survival following testicular damage. In this study, a F0 gestation DEHP exposure and transgenerational inheritance testis injury model was established to study the testis injury phenotype and the expression and activation of members of PI3K/Akt/mTOR signaling pathway in the testis of F1-F3 generation mice. We found that the bodyweight and the anogenital distance (AGD) are reduced only in F1 mice, the sperm motility and deformity decreased in F1-F3 mice, and the testicular histomorphology damagedin F1-F3 mice; however the sperm motility and deformity rates are increased and the histomorphological injury is repaired during the transgenerational process. We also found the activation of PI3K/Akt/mTOR signaling pathway is enhanced in F1 and F2, and the number of apoptotic cells is decreased in F3 generation mice compared to the control group. These results suggest that the PI3K/Akt/mTOR signaling pathway may be activated to promote the proliferation and differentiation and protect testicular cells from apoptosis in the F1 and F2 generation mice after direct exposure to DEHP.

Alternating Sequence Control for Poly(ester amide)s by Organocatalyzed Ring-Opening Polymerization.

Sequence-controlled polymerization is the forefront of polymer chemistry. Herein, the feasibility of sequence regulation by using organocatalyzed ring-opening polymerization (ROP) is demonstrated. In particular, ring expansion strategy is employed to synthesize pre-organized monomers 1 and 2. ROP is conducted by using 1,5,7-triazabicyclo[4.4.0]dec-5-ene and benzyl alcohol as the catalyst and initiator, respectively. Poly(ester amide)s (PEAs) P1-P3 comprising glycolic acid, lactic acid, and 7-aminoheptanoic acid units are obtained in high molecular weights and good yields. NMR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry results verify the microstructural integrity of P1 and P2. Differential scanning calorimetry results show that PEA without methyl branches is crystalline. Moreover, thermal stability, surface wettability, and degradation profiles of P1-P3 are also investigated.

Endoplasmic reticulum stress, a novel significant mechanism responsible for DEHP-induced increased distance between seminiferous tubule of mouse testis.

Di(2-ethylhexyl) phthalate (DEHP), a widely existed endocrine disruptor, has been concerned for many years owing to its toxicity in male reproductive development. In this study, we investigated the reproductive effects and the mechanism of mouse testis after in uterus exposure to the plasticizer DEHP. We found that the UPR signaling pathway could be fully activated after DEHP treatment. In uterus DEHP exposure significantly increased abnormal morphology seminiferous tubules, expanded the distance between the tubules as well as caused abnormal endoplasmic reticulum (ER) ultrastructure, which could be reversed by 4-phenylbutyrate (4-PBA), an ER stress inhibitor. In addition, DEHP-induced ER stress pathway promoted a decline in protein expression, including cadherin protein N-cadherin in testis, which could also be reversed by 4-PBA. Taken together, our results provide compelling evidence that the ER stress would be a novel significant mechanism responsible for DEHP-induced the increased the distance between seminiferous tubule by reducing the N-cadherin expression.