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ObjectivesTo assess the lateralization of cerebral blood flow (CBF) in the auditory cortex of idiopathic tinnitus patients and healthy controls (HCs) using 3D pseudocontinuous arterial spin labeling (pcASL).MethodsThirty-six patients with idiopathic tinnitus and 43 sex- and age-matched HCs underwent 3D-pcASL scanning using a 3.0 T MRI system. For both groups, region of interest analysis was performed on the primary auditory cortex (PAC), auditory associative cortex (AAC), and secondary auditory cortex (SAC). The clinical data of all subjects were analyzed.ResultsIn both tinnitus patients and HCs, CBF of the left PAC was significantly higher than that of the right (HCs: P = 0.02; patients: P = 0.043), but CBF of the right AAC and SAC was significantly higher than that of the left (AAC: HCs, P < 0.001; patients: P < 0.001. SAC: HCs, P < 0.001; patients: P = 0.001). Compared with HCs, tinnitus patients exhibited significantly higher CBF in the bilateral PAC (right: P = 0.008; left: P = 0.022). CBF in the left PAC was positively correlated with tinnitus severity (r = 0.399, P = 0.016).ConclusionThis study confirms the asymmetry of the auditory cortex and investigates the underlying neuropathology of idiopathic tinnitus in terms of CBF.

BackgroundLittle is known regarding the role of responsive caregiving in the association between maternal psychological stress and child neurodevelopment. We, therefore, herein investigated the relationship between maternal psychological stress during pregnancy and children's neurodevelopment with modifications in responsive caregiving.MethodsA total of 3,603 mother–child pairs were recruited from the Shanghai Maternal-Child Pairs Cohort, and we assessed maternal psychological stress using the Life Events Scale for Pregnant Women (LESPW) during early and late pregnancy. Early neurodevelopment of infants at 6 and 12 months of age was also evaluated using the Age and Stage Questionnaire, Third Edition (ASQ-3). The 2-month-old infant nursing-care questionnaire was designed based on the Five Elements of Parenting Care Framework released by the World Health Organization (WHO) and used to evaluate the levels of early responsive caregiving for infants. Multivariate logistic regression analysis was then applied to determine the association between maternal psychological stress during pregnancy and child development.ResultsThe suspected developmental delay rate of infants aged 6 and 12 months ranged between 13.3% and 24.5%. After adjusting for confounders, we noted that high maternal subjective events stress during early pregnancy was associated with an increased risk of suspected developmental delay in problem-solving domains at 12 months of age [adjusted OR (aOR) = 1.51; 95% confidence interval (CI), 1.09–2.20]. High general negative objective events’ stress during late pregnancy also constituted a risk factor for development in the personal–social domain at 12 months of age (aOR = 1.57; 95% CI, 1.13–2.19). Remarkably, we noted in infants with insufficient responsive caregiving that there were greater associations between the risk of general maternal negative objective events during late pregnancy and personal–social domain at 12 months of age (aOR = 2.06; 95% CI, 1.15–3.68). Similarly, there was a greater association between the risk for maternal subjective events during early pregnancy and problem-solving at 12 months of age (aOR = 1.55; 95% CI, 1.11–2.34).ConclusionsMaternal psychological stress during pregnancy was predominantly associated with suspected developmental delay in infants at 6 and 12 months of age, and these associations were modified by early responsive caregiving.

BackgroundInfant development shapes children’s health into adulthood. Although providing responsive caregiving and opportunities regarding early learning for infants have received increasing attention from the international community, few studies have been published on these topics thus far. The purpose of the present study, then, was to explore the influences of responsive caregiving and the opportunities for early learning on infant development.MethodsMother-child dyads (3,714 pairs) were recruited from the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC) for the present study, and the development of infants, responsive caregiving and opportunities for early learning were collected from three waves of follow-up (2-, 6-, and 12-month old) We used the cross-lagged model to analyze the longitudinal correlation between responsive caregiving or opportunities for early learning and development of infants. We used the generalized estimation equation (GEE) to evaluate the effect of responsive caregiving and opportunities for early learning on suspected developmental delay; we also conducted a hierarchical analysis to investigate the interaction between responsive caregiving or opportunities for early learning and annual family income.ResultsThere was a mutual prediction between responsive caregiving or opportunities for early learning and some developmental domains of the Ages and Stages Questionnaires, third edition (ASQ-3). Sustained high-exposure to responsive caregiving or opportunities for early learning significantly decreased the risk of suspected developmental delay in most domains of the ASQ-3. And For infants whose annual family income was < ¥200,000, sustained high-exposure (Adjusted Odds Ratio = 0.456, 95% CI, 0.325–0.638) and fluctuating-exposure (Adjusted Odds Ratio = 0.510, 95% CI, 0.414–0.627) to responsive caregiving significantly reduced the risk for suspected developmental delay.ConclusionResponsive caregiving or opportunities for early learning interacted with infant development. Infants’ early access to adequate responsive caregiving and opportunities for early learning exerted a sustained and positive impact on infant development, and this effect is more pronounced in relative low-income families.

As a deubiquitination (DUB) enzyme, ubiquitin-specific protease 13 (USP13) is involved in a myriad of cellular processes, such as mitochondrial energy metabolism, autophagy, DNA damage response, and endoplasmic reticulum-associated degradation (ERAD), by regulating the deubiquitination of diverse key substrate proteins. Thus, dysregulation of USP13 can give rise to the occurrence and development of plenty of diseases, in particular malignant tumors. Given its implications in the stabilization of disease-related proteins and oncology targets, considerable efforts have been committed to the discovery of inhibitors targeting USP13. Here, we summarize an overview of the recent advances of the structure, function of USP13, and its relations to diseases, as well as discovery and development of inhibitors, aiming to provide the theoretical basis for investigation of the molecular mechanism of USP13 action and further development of more potent druggable inhibitors.

Background: The late occurrence of adiposity peak (AP) and the early occurrence of adiposity rebound (AR) are considered the earliest indicators for obesity and its related health conditions later in life. However, there is still limited information for their upstream factors. Therefore, in this study, we aimed to identify the parental and child factors associated with the timing of AP and AR in the early stage of life.Methods: This is a population-based longitudinal study conducted in Shanghai, China. The BMI data of children born between September 2010 and October 2013 were followed from birth to 80 months. Subject-specific body mass index trajectories were fitted by non-linear mixed-effect models with natural cubic spline functions, and the individual's age at AP and AR was estimated. The generalized linear regression models were applied to identify the upstream factors of late occurrence of AP and early occurrence AR.Results: For 7,292 children with estimated AP, boys were less likely to have a late AP [adjusted risk ratio (RR) = 0.83, 95% confidence interval (CI): 0.77–0.90, p < 0.001], but preterm born children had a higher risk of a late AP (adjusted RR = 1.25, 95% CI: 1.07–1.47, p < 0.01). For 10,985 children with estimated AR, children with breastfeeding longer than 4 months were less likely to have an early AR (adjusted RR = 0.80, 95% CI: 0.73–0.87, p < 0.001), but children who were born to advanced-age mothers and who were born small for gestational age had a higher risk of having an early AR (adjusted RR = 1.21, 95% CI: 1.07–1.36, p < 0.01; adjusted RR = 1.20, 95% CI: 1.04–1.39, p = 0.01).Conclusions: Modifiable pre-birth or early-life factors associated with the timing of AP or AR were found. Our findings may help develop prevention and intervention strategies at the earliest stage of life to control later obesity and the health conditions and diseases linked to it.