The pandemic of coronavirus disease 2019 (COVID-19) has been the foremost modern global public health challenge. The airway is the primary target in severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection, with substantial cell death and lung injury being signature hallmarks of exposure. The viral factors that contribute to cell death and lung injury remain incompletely understood. Thus, this study investigated the role of open reading frame 7b (Orf7b), an accessory protein of the virus, in causing lung injury. In screening viral proteins, we identified Orf7b as one of the major viral factors that mediates lung epithelial cell death. Overexpression of Orf7b leads to apoptosis and ferroptosis in lung epithelial cells, and inhibitors of apoptosis and ferroptosis ablate Orf7b-induced cell death. Orf7b upregulates the transcription regulator, c-Myc, which is integral in the activation of lung cell death pathways. Depletion of c-Myc alleviates both apoptotic and ferroptotic cell deaths and lung injury in mouse models. Our study suggests a major role of Orf7b in the cell death and lung injury attributable to COVID-19 exposure, supporting it as a potential therapeutic target.
Purpose The aim of this paper is to enhance the control performance of dexterous hands, enabling them to handle the high data flow from multiple sensors and to meet the deployment requirements of deep learning methods on dexterous hands. Design/methodology/approach A distributed control architecture was designed, comprising embedded motion control subsystems and a host control subsystem built on ROS. The design of embedded controller state machines and clock synchronization algorithms ensured the stable operation of the entire distributed control system. Findings Experiments demonstrate that the entire system can operate stably at 1KHz. Additionally, the host can accomplish learning-based estimates of contact position and force. Originality/value This distributed architecture provides foundational support for the large-scale application of machine learning algorithms on dexterous hands. Dexterity hands utilizing this architecture can be easily integrated with robotic arms.
Vitamin B12 (B12) adequacy during pregnancy is crucial for maternal health and optimal fetal development; however, suboptimal B12 status has been reported in pregnant Canadian women. Methylmalonic acid (MMA) is a sensitive indicator of B12 status. Since few studies have measured MMA during pregnancy in Canadian women, the objective of this study was to evaluate B12 status in pregnant women living in Metro Vancouver, using both plasma total B12 and MMA. We recruited a convenience sample of 320 pregnant women between 20 and 35 gestational weeks from local healthcare facilities. Plasma total B12 concentrations indicative of deficiency (<148 pmol/L) and suboptimal B12 status (148-220 pmol/L) were found in 18% and 33% of the women, respectively. Normal plasma MMA concentration (<210 nmol/L) was observed in 82% of all women. Gestational age was a strong predictor of plasma total B12 and MMA concentration, and South Asian ethnicity of B-12 deficiency and MMA concentrations. Overall, there was a high discrepancy between the prevalence of B12 inadequacy depending on the biomarker used. Independently, however, South Asian women were at particular risk for B12 deficiency, likely due to lower animal source food intake. Further study of this vulnerable group and performance testing of B12 biomarkers is warranted.
Background Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor used in renal anemia treatment, has been associated with thyroid hormone suppression. This study investigated the patterns of thyroid profile changes following roxadustat administration and their clinical implications. Methods In this retrospective study (2019-2023) at Shenzhen Second People's Hospital, patients were categorized based on TSH reduction during follow-up (≥50% decrease vs<50% decrease). Thyroid profiles, clinical symptoms, and laboratory indicators were analyzed. Quality of life was assessed using EQ-5D-3L and ThyPRO questionnaires. Complementary animal experiments were conducted to verify the effects of roxadustat on thyroid function. Results A total of 118 patients were finally enrolled in our study. Among patients with initially normal thyroid function, 31 developed euthyroid sick syndrome post-roxadustat treatment. Treatment significantly decreased T3, FT3, FT4, and TSH levels, with TSH showing marked reduction within the first 10 weeks. Contrastingly, animal models exhibited decreased T3 but increased TSH levels, regardless of renal status. Blood lipid levels decreased in all patients, particularly in those with substantial TSH reduction. Despite thyroid alterations, quality of life scores remained unchanged between roxadustat-treated and untreated patients, with no overt clinical symptoms in either humans or animals. Conclusions While roxadustat induces significant thyroid hormone suppression in patients, these alterations rarely manifest as clinical symptoms. Euthyroid sick syndrome is the predominant thyroid dysfunction pattern observed. Regular thyroid function monitoring is recommended during roxadustat therapy, particularly during the initial treatment phase when TSH changes are most pronounced.
Abstract Background Vitamin D deficiency during infancy may lead to rickets and possibly other poor health outcomes. The World Health Organization recommends exclusive breastfeeding for the first 6 months. Breast milk is the best food for infants but does not contain adequate vitamin D. Health Canada recommends all breastfed infants receive a daily vitamin D supplement of 400 IU; however, there appears to be limited current Canadian data as to whether parents or caregivers are following this advice. The aim of this study was to determine the rates of vitamin D supplementation among 2-month old infants in Vancouver and Richmond, British Columbia, Canada. Methods Mothers of all healthy infants born between April and May 2010 were approached to participate. Telephone surveys were conducted with 577 mothers (response rate 56%) when their infants turned 2 months. Results Over half of the infants received only breast milk in the week prior to the survey. One third received a mixture of breast milk and infant formula and 10% received only formula. About 80% of the infants were supplemented with vitamin D at 2 months. Infants who received only breast milk were most likely to be supplemented with vitamin D (91%). Over 60% of the infants had a total vitamin D intake of 300- < 500 IU/d from supplements and formula and only 5% did not receive any vitamin D. Most parents were advised to give vitamin D supplement by health professionals, such as public health nurses, midwives, and doctors. Conclusions About 90% of the infants received breast milk at 2 months of age. The vitamin D supplementation rate was 80%. Future studies are needed to monitor breastfeeding duration and vitamin D supplementation rates as infants get older.
Mesenchymal Stem Cells (MSCs) therapy has become a new coming focus of clinical research in regenerative medicine. However, only a small number of implanted MSCs could successfully reach the injured areas. The previous studies have shown that fracture healing time is inversely proportional to concentration of MSCs in injured tissue.The migration and osteogenesis of MSCs were assessed by transwell assay and Alizarin Red S staining. Levels of gene and protein expression were checked by qPCR and Western Blot. On the other hand, the enhanced migration ability of MSCs induced by Cyasterone was retarded by CXCR4 siRNA. In addition, the rat model of femoral fracture was established to evaluate the effect of Cyasterone on fracture healing. What's more, we also checked the effect of Cyasterone on mobilisation of MSCs in vivo.The results showed that Cyasteron increased the number of MSCs in peripheral blood. The concentrations of SDF-1α in serum at different time points were determined by ELISA assay. Micro-CT and histological analysis were used to evaluate the fractured femurs.Our results showed that Cyasterone could promote the migration and osteogenesis capacities of MSCs. The fractured femurs healed faster with treatment of Cyasterone. Meanwhile, Cyasterone could significantly increase the level of SDF-1α in rats with femur fracture.Cyasterone could promote migration and osteogenesis of MSCs, and most importantly, it could accelerate bone fracture healing.Translational Potential statement: These findings provide evidence that Cyasterone could be used as a therapeutic reagent for MSCs mobilisation and osteogenesis. What's more, it could acclerate fracture healing.
To identify risk factors of admission deep vein thrombosis (DVT) in patients with traumatic fractures. Medical records of 1596 patients with traumatic fractures were reviewed. According to the ultrasound reports of the lower extremity veins, patients were assigned to the DVT or non-DVT group. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors of DVT, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of the D-dimer level for DVT. DVT admission incidence was 20.67%. Statistically significant differences were revealed between the 2 groups in terms of age, sex, fracture site, presence of hypertension, coronary heart disease, stroke, smoking status, time from injury to admission, and levels of fasting blood glucose, hemoglobin, fibrinogen, D-dimer, and hematocrit. Multivariate analysis results showed that age above 50 years, female, above-knee fracture, cigarette smoking, injury-to-admission delay beyond 48 h, low hemoglobin levels, high fasting blood glucose levels, and high D-dimer levels were independent risk factors for admission DVT. ROC analysis showed that the D-dimer level was effective for the prediction of admission DVT in patients with peri-knee and below-knee fractures (area under the curve [AUC] = 0.7296, cutoff point = 1.21 mg/L). An age over 50 years, female, above-knee fracture, smoking, injury-to-admission delay beyond 48 h, decreased hemoglobin level, and increased fasting blood glucose and D-dimer levels were found to be potential independent risk factors for admission DVT. In patients with peri-knee and below-knee fractures, the plasma D-dimer level was effective in predicting admission DVT.
Recent studies suggest Canadian children from immigrant families may be at higher risk for rickets. However, little is known about the vitamin D status of immigrant mothers and infants in Canada. We measured 25‐hydroxyvitamin D (25OHD) in Asian and Middle Eastern immigrant (n=40) and White (n=40) mothers and their infants aged 2–4 months living in Vancouver (49°N). Mothers completed diet and sun exposure questionnaires. Mean 25OHD concentrations of immigrant mothers were lower than those of White mothers (68 vs 78 nmol/L; p=0.02), but 25OHD concentrations of their babies did not differ (82 vs 79 nmol/L; p=0.67). Only 1 White mother, 1 infant with a White mother, and 1 infant with a Middle Eastern mother had a 25OHD concentration indicative of severe deficiency (<25 nmol/L). However, 7 (18%) immigrant mothers and 2 (5%) White mothers (p=0.08) and 3 (8%) immigrants’ infants and 6 (15%) White infants (p=0.29) were vitamin D insufficient (<50 nmol/L). Multivariate analyses showed that ethnicity, body mass index, and vitamin D supplement use were significant predictors of 25OHD in mothers. Only supplement use was a significant predictor for infants. In conclusion, immigrant mothers were at marginally higher risk of vitamin D insufficiency than White mothers, but their infants had similar vitamin D status. (Supported by the Canadian Vitamin Class Action settlement) Grant Funding Source : Canadian Vitamin Class Action settlement
Family socioeconomic status (SES) differences in early childhood development (ECD) are well documented, as are the neighborhood effects in early development outcomes. However, little is known about whether the SES gradient in ECD outcomes varies across geographic contexts by county-level variables in contemporary China. This study examines the effects of county-level socioeconomic background on inequalities in the developmental outcomes of young Chinese children. Individual-level child development data based on four early development milestones—taking a first step, first sentences, counting 10 objects, fully independent toileting—were combined with family- and county-level socioeconomic data from the China Family Panel Studies (CFPS). Using a hierarchical linear model (HLM) to examine how the broader socioeconomic context plays a role in the attainment of developmental milestones at expected times as young children grow and develop, we have found significant cross-level interaction effects between family SES and county-level variables in relation to developmental milestone attainment. The family SES gradient in the achievement of children’s developmental milestones is steeper for those in the under-developed regions than their counterparts in the more developed regions. Our findings suggest that low-SES children who are living in socioeconomically deprived regions suffer from a double disadvantage in terms of early development outcomes. Further research would be needed to contextualize the observed interactions and better explain the underlying mechanisms.
It has been well documented that East Asian students in primary and secondary education academically outperform their Western counterparts. One prominent explanation points to the role of culture. This study explores the cultural explanation from a comparative perspective. Analyzing data from mainland China, Taiwan, South Korea, the U.S., Germany, and Australia, we examine the variation across social contexts in the importance of family SES to parents' and children's educational expectations, paying particular attention to comparison between East-Asian and Western societies. We find that educational expectations are much less dependent on family background in East Asian societies than in the West, in that parents and children in the former all tend to hold high educational expectations, irrespective of family socioeconomic status.
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