SARS-CoV-2 BA.2 (Omicron) variant infection in pediatric liver transplanted recipients and cohabitants during 2022 Shanghai outbreak: a prospective cohort.

BACKGROUND: The Omicron variant BA.2 was the dominant variant in the COVID-19 outbreak in Shanghai since March 2022. We aim to investigate the characteristics of SARS-CoV-2 Omicron variant infection in pediatric liver-transplanted recipients. METHODS: We conducted a single-center, prospective, observational, single-arm study. We enrolled pediatric liver-transplanted patients infected with the Omicron variant BA.2 from March 19th to October 1st, 2022 and analyzed their demographic, clinical, laboratory, and outcome data. The management of COVID-19 was conducted according to the 9th trial edition of the Chinese guideline. The immunosuppressive therapy was tailored considering the patients' infection developments and liver functions. RESULTS: Five children were included. The primary diseases included Niemann-Pick disease, propionic acidemia, decompensated cirrhosis, biliary atresia, and Crigler-Najjar syndrome type I. All of the patients were onset with fever before or when getting RNA-positive results at the age of 3 (Range: 1-13) years. The infection duration was 29 (Range: 18-40) days. Three and two children were diagnosed with mild and moderate COVID-19 respectively. Two patients were tested RNA-positive within 14 days after having been tested negative. The immunosuppressants were paused or extenuated in four patients. Eight of all nine cohabitants were injected with at least two doses of inactivated SARS-CoV-2 vaccine. The disease courses were significantly longer than the patients (P < 0.05). CONCLUSIONS: Post-transplant immunosuppression slows down the virus clearance and increases the risk of relapse but does not affect symptom duration or infection severity in pediatric patients. Patients can usually gain a favorable outcome and prognosis by extenuating immunosuppressants.

A closed-circuit cycle process for recovery of carbon and valuable components from spent carbon cathode by hydrothermal acid-leaching method.

Spent carbon cathode (SCC) as a hazardous solid waste produced in aluminum electrolysis industry, contains plenty valuable components but generate a seriously threat to the environment. This paper focus on a closed-circuit cycle process for direct treatment of SCC based on the hydrothermal acid-leaching method. Thermodynamic calculation, single factor experiment, orthogonal experiment and kinetic study are utilized to obtain the leaching properties of impurities, optimize the leaching conditions, study the influence of conditions on leaching, and capture the restriction factors of leaching. The results indicate that the carbon content of the treated SCC can reach 97.3% when the leaching condition attach the optimal (liquid-solid ratio of 25 mL/g, temperature of 413 K, time of 270 min and acid concentration of 4 mol/L), and liquid-solid ratio is regarded as the crucial factor influencing on that. In addition, the activation energy of impurities reaches 6.25 kJ/mol and the whole leaching process is controlled by the diffusion extent. Finally, the filtrate after the hydrothermal acid leaching is treated, and calcium fluoride, cryolite and sodium chloride are successfully separated. The proposed process eliminates the harm of SCC to the environment, and completes a closed-circuit cycle for the treatment of SCC and recovery of valuable components. It enriches the hydrometallurgical processes of SCC, and provides an attractive scheme for the treatment of SCC.

Zinc transporter ZIP12 maintains zinc homeostasis and protects spermatogonia from oxidative stress during spermatogenesis.

BACKGROUND: Overwhelming evidences suggest oxidative stress is a major cause of sperm dysfunction and male infertility. Zinc is an important non-enzymatic antioxidant with a wide range of biological functions and plays a significant role in preserving male fertility. Notably, zinc trafficking through the cellular and intracellular membrane is mediated by specific families of zinc transporters, i.e., SLC39s/ZIPs and SLC30s/ZnTs. However, their expression and function were rarely evaluated in the male germ cells. The aim of this study is to determine and characterize the crucial zinc transporter responsible for the maintenance of spermatogenesis. METHODS: The expression patterns of all 14 ZIP members were characterized in the mouse testis. qRT-PCR, immunoblot and immunohistochemistry analyses evaluated the ZIP12 gene and protein expression levels. The role of ZIP12 expression was evaluated in suppressing the sperm quality induced by exposure to an oxidative stress in a spermatogonia C18-4 cell line. Zip12 RNAi transfection was performed to determine if its downregulation altered cell viability and apoptosis in this cell line. An obese mouse model fed a high-fat-diet was employed to determine if there is a correlation between changes in the ZIP12 expression level and sperm quality. RESULTS: The ZIP12 mRNA and protein expression levels were higher than those of other ZIP family members in both the mouse testis and other tissues. Importantly, the ZIP12 expression levels were very significantly higher in both mice and human spermatogonia and spermatozoa. Moreover, the testicular ZIP12 expression levels significantly decreased in obese mice, which was associated with reduced sperm zinc content, excessive sperm ROS generation, poor sperm quality and male subfertility. Similarly, exposure to an oxidative stress induced significant declines in the ZIP12 expression level in C18-4 cells. Knockdown of ZIP12 expression mediated by transfection of a ZIP12 siRNA reduced both the zinc content and viability whereas apoptotic activity increased in the C18-4 cell line. CONCLUSIONS: The testicular zinc transporter ZIP12 expression levels especially in spermatogonia and spermatozoa are higher than in other tissues. ZIP12 may play a key role in maintaining intracellular zinc content at levels that reduce the inhibitory effects of rises in oxidative stress on spermatogonia and spermatozoa viability during spermatogenesis which help counteract declines in male fertility.

Investigation on the hesitancy of COVID-19 vaccination among liver transplant recipients: A cross-sectional study in China.

Objectives: The hospitalization and mortality rate from COVID-19 appears to be higher in liver transplant recipients when compared with general populations. Vaccination is an effective strategy to reduce the risk during the COVID-19 pandemic. We aimed to evaluate COVID-19 vaccine hesitancy in liver transplant recipients. Methods: In April 2022, we conducted an online-based survey through WeChat platform to investigate the vaccination hesitancy among liver transplant recipients followed at Shanghai Renji Hospital and further explore possible influencing factors. Survey items included multiple choice, Likert-type rating scale and open-ended answers. Participants were classified as no hesitancy group and hesitancy group. Using univariate analysis, ROC curve analysis and multiple logistic regression to evaluate associations between baseline characteristics and COVID-19 vaccine hesitancy. Results: 449 liver transplant recipients participated in the survey with 299 (66.6%) of them being categorized as vaccine hesitancy. In no hesitancy group, 73 (48.7%) recipients had completed vaccination, while 77 (51.3%) were not yet but intended to be vaccinated. In contrast, 195 (65.2%) recipients in hesitancy group were hesitant to get vaccinated, while the remaining 104 (34.8%) refused. The most common side effect was injection arm pain (n = 9, 12.3%). The common reasons for vaccine willingness was trusted in the effectiveness of the vaccine and fear of contracting COVID-19. The most common reason for vaccination hesitancy is fear of side effects, and the most effective improvement was the support from the attending physician. Factors associated with vaccine hesitancy include female sex, influenza vaccination status, awareness of the importance and safety of vaccine, attitudes of doctors and others toward vaccine, medical worker source information of vaccine, relative/friend with medical background, total score of VHS (Vaccine Hesitancy Scale), accessibility of vaccine. Conclusion: For liver transplant recipients, COVID-19 vaccine is an important preventive measure. Identifying the factors influencing COVID-19 vaccine hesitancy is therefore critical to developing a promotion plan. Our study shows that more comprehensive vaccine knowledge popularization and relevant medical workers' training can effectively improve the acceptance of COVID-19 vaccine in this population.

The underlying risks of circadian blood pressure variation for carotid plaque in treated hypertensive patients with normal blood pressure.

OBJECTIVES: The aim of this study was to investigate the relationship between 24 h variation of blood pressure (BP) and carotid plaque in essential hypertensive patients with normal BP under anti-hypertensive treatment. PARTICIPANTS AND METHODS: A total of 322 hypertensive patients with systolic BP (SBP) and diastolic BP (DBP) within the normal range after routine treatment were continuously recruited and evaluated by ambulatory BP monitoring from 1 January 2014 to 31 July 2015. The exclusion criteria included participants younger than 18 or older than 90 years of age, pregnancy, night-work employment, and suffering from secondary hypertension. The prevalence of carotid plaque between different circadian BP pattern groups was analyzed using a χ-test. Logistic regression was applied to analyze the relationship between carotid plaque and ambulatory BP monitoring variables. RESULTS: All the individuals were divided into a 'carotid plaque' group (n=197) and a 'non-plaque' group (n=125) on the basis of whether the thickness of each plaque was at least 0.5 mm under the carotid ultrasound. In addition, patients were grouped into a dipper (10-20% nocturnal fall of BP in SBP) group and a nondipper (<10% nocturnal fall of BP in SBP) group on the basis of individual SBP variation. In the nondipper group, the number of patients with carotid plaque was higher than the patients without plaque (P=0.017). Logistic analysis showed that the nondipper pattern of BP was significantly associated with the formation of carotid plaque (odds ratio=1.731, P=0.041). CONCLUSION: A nondipper pattern of BP may serve as a risk factor for carotid plaque in treated hypertensive individuals with normal BP.

Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway.

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disorder with high morbidity and mortality, and is characterized by excessive growth of endothelial cells. Recently, the mammalian target of rapamycin (mTOR) has attracted increasing attention due to its potential as a therapeutic target against certain diseases associated with proliferative and metabolic abnormalities. However, the effect on mTOR on PAH has not yet been elucidated. In the present study, a marked downregulation of mTOR was observed in PAH patients. Following construction of a mouse model of PAH by chronic exposure to hypoxia, adenovirus-mediated upregulation of mTOR significantly attenuated right ventricular systolic pressure, right ventricular hypertrophy and wall thickness of pulmonary arterioles, indicating a protective effect of mTOR on PAH. Further analysis confirmed that mTOR overexpression inhibited autophagy triggered by hypoxia through blocking light chain 3 II expression and increasing p62 levels. In vitro, hypoxia enhanced the proliferation of human pulmonary artery endothelial cells (PAECs), which was markedly abrogated by mTOR overexpression. Of note, upregulation of mTOR inhibited the hypoxia-induced autophagy pathway, which contributed to cell proliferation, while silencing of autophagy by RNA interference with ATG5 significantly inhibited cell proliferation. In conclusion, the results of the present study suggested a potential protective effect of mTOR on the progression of PAH by suppressing PAEC proliferation through blocking the autophagic pathway. Therefore, the present study suggested that mTOR is a promising therapeutic agent against PAH.

Knockdown of mTOR by lentivirus­mediated RNA interference suppresses atherosclerosis and stabilizes plaques via a decrease of macrophages by autophagy in apolipoprotein E­deficient mice.

Atherosclerotic plaque destabilization and rupture leads to acute coronary syndromes which cause serious damage to human health worldwide. However, there is currently a lack of efficient therapeutic methods. Mammalian target of rapamycin (mTOR) has been suggested to be involved in the development of atherosclerotic plaques and serves as a therapeutic target. The present study was performed to determine whether RNA interference (RNAi) of mTOR in vivo by LV­mediated small hairpin RNA (shRNA) was capable of inhibiting the progression of atherosclerotic plaques. LV­mediated shRNA against mTOR (LV­shmTOR) was designed and obtained. Male apolipoprotein E­deficient mice were fed a high­fat diet and a constrictive collar was placed around the right carotid arteries of these mice to induce plaque formation. Eight weeks after surgery, mice were randomly divided into the mTOR RNA interference (LV­shmTOR) group, receiving treatment with LV­mTOR­shRNA; the LV­shCON group, receiving treatment with LV­non­specific­shRNA; and the control group, receiving treatment with phosphate­buffered saline. Following transfection, the mice were sacrificed to evaluate the effects of mTOR expression silencing on atherosclerosis. Transfection of LV­mTOR­shRNA markedly inhibited the mRNA and protein expression levels. Knockdown of mTOR ameliorated dysregulated blood lipid metabolism and stabilized aortic atherosclerotic plaques by decreasing the plaque area and increasing the fibrous cap and cap­to­core ratio. Furthermore, macrophages were decreased by silencing mTOR in atherosclerotic plaques. In addition, western blot analysis revealed that the knockdown of mTOR increased autophagy­related protein 13 (Atg13) dephosphorylation and light chain 3­I/light chain 3­II (LC3­I/LC3­II) ratios, both of which were associated with a high activity of autophagy, suggesting an increase of autophagy in atherosclerotic plaques. Moreover, genes including matrix metalloproteinase 2, monocyte chemoattractant protein 1 and tissue factor, which promote plaque instability, were downregulated by silencing mTOR. These results demonstrate that LV­mediated mTOR silencing by RNAi treatment induces macrophage autophagy and is a potential strategy for the treatment of atherosclerotic plaques.