Long-term effects of Omicron BA.2 breakthrough infection on immunity-metabolism balance: a 6-month prospective study.

There have been reports of long coronavirus disease (long COVID) and breakthrough infections (BTIs); however, the mechanisms and pathological features of long COVID after Omicron BTIs remain unclear. Assessing long-term effects of COVID-19 and immune recovery after Omicron BTIs is crucial for understanding the disease and managing new-generation vaccines. Here, we followed up mild BA.2 BTI convalescents for six-month with routine blood tests, proteomic analysis and single-cell RNA sequencing (scRNA-seq). We found that major organs exhibited ephemeral dysfunction and recovered to normal in approximately six-month after BA.2 BTI. We also observed durable and potent levels of neutralizing antibodies against major circulating sub-variants, indicating that hybrid humoral immunity stays active. However, platelets may take longer to recover based on proteomic analyses, which also shows coagulation disorder and an imbalance between anti-pathogen immunity and metabolism six-month after BA.2 BTI. The immunity-metabolism imbalance was then confirmed with retrospective analysis of abnormal levels of hormones, low blood glucose level and coagulation profile. The long-term malfunctional coagulation and imbalance in the material metabolism and immunity may contribute to the development of long COVID and act as useful indicator for assessing recovery and the long-term impacts after Omicron sub-variant BTIs.

Noncanonical Wnt5a Signaling Suppresses Hippo/TAZ-Mediated Osteogenesis Partly Through the Canonical Wnt Pathway in SCAPs.

PURPOSE: Stem cells from the apical papilla (SCAPs) are promising seed cells for tissue regeneration medicine and possess the osteogenic differentiation potential. Wnt5a, a typical ligand of the noncanonical Wnt pathway, exhibits diverse roles in the regulation of osteogenesis. The transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1) is a core regulator in the Hippo pathway and regulates stem behavior including osteogenic differentiation. This study aims to examine how Wnt5a regulates SCAPs osteogenesis and explore the precise mechanistic relationship between Wnt5a and TAZ. METHODS: SCAPs were isolated from developing apical papilla tissue of extracted human immature third molars in vitro. ALP staining, ALP activity and Alizarin red staining were used to evaluate osteogenic capacity. Osteogenic-related factors were assessed by qRT-PCR or Western blotting. Additionally, the receptor tyrosine kinase-like orphan receptor 2 (ROR2) was detected by immunocytofluorescence staining and silenced by small interfering RNA to verify the function of Wnt5a/ROR2 in TAZ-mediated osteogenesis. And we constructed TAZ-overexpression and ß-catenin-overexpression SCAPs generated by lentivirus to explore the precise mechanistic relationship between Wnt5a and TAZ. RESULTS: Wnt5a (100ng/mL) significantly suppressed ALP activity, mineralization nodules formation, expression of osteogenic-related factors. Meanwhile, it decreased the expression of TAZ mRNA and protein. TAZ overexpression promoted osteogenesis of SCAPs while Wnt5a could block TAZ-mediated osteogenesis. Furthermore, ROR2 siRNA (siROR2) was found to upregulate TAZ and canonical Wnt pathway signaling related molecules such as ß-catenin, GSK3ß and p-GSK3ß. The suppression of Wnt5a/ROR2 on osteogenesis was significantly reversed by ß-catenin overexpression through Wnt5a/ROR2/ß-catenin/TAZ pathway. CONCLUSION: Taken together, the present study demonstrates that Wnt5a suppresses TAZ-mediated osteogenesis of SCAPs and there may be a Wnt5a/ROR2/ß-catenin/TAZ pathway regulating osteogenesis of SCAPs. Moreover, Wnt5a could be a candidate for regulators in tissue regeneration.

China's carbon emissions from the electricity sector: Spatial characteristics and interregional transfer.

As a major carbon emitter, the electricity sector is crucial to the realization of China's emission reduction objectives. Existing studies focus mostly on the influencing factors, emission efficiency and low carbon development of carbon emissions in the electricity sector. Missing from the literature is an analysis of spatial characteristics of carbon emissions and the embodied carbon emission transfer caused by the separation of electricity production and consumption, which is the basis for assigning the responsibility for emission reduction. Thirty provinces in China were taken as research objects, and Moran's I index was adopted to analyze the spatial characteristics of the electricity sector's carbon emissions and carbon emission intensity. Based on multiregional input-output tables, we compared the transfer situation of China's provincial electricity carbon emissions in 2010 and 2015. The results demonstrate that, from 2010 to 2015, the electricity carbon emissions in 20 provinces increased, whereas the carbon emission intensity in 21 provinces decreased. Carbon emissions and carbon emission intensity of electricity in most provinces demonstrate positive spatial clustering characteristics. The total amount of carbon emission transfer in the electricity sector increased from 421.22 million tons in 2010 to 581.369 million tons in 2015, the number of net transfers out of areas increased from 13 to 15, and the number of net transfers into areas decreased from 16 to 15. The active degree of carbon emission transfer reveals the eastern region > the central region > the western region. Different emission reduction policies should be formulated based on the difference in resource endowment between the north and south. Provinces that transferred out large amounts of electricity carbon emissions should take greater responsibility for emission reduction. Integr Environ Assess Manag 2022;18:258-273. © 2021 SETAC.

Exosomal microRNA-98-5p from hypoxic bone marrow mesenchymal stem cells inhibits myocardial ischemia-reperfusion injury by reducing TLR4 and activating the PI3K/Akt signaling pathway.

OBJECTIVE: MicroRNAs (miRNAs) are essential biomarkers during development of human diseases. We aimed to explore the role of hypoxia-induced bone marrow mesenchymal stem cells (BMSCs)-derived exosomal miR-98-5p in myocardial ischemia-reperfusion injury (MI/RI). METHODS: BMSCs were isolated, cultured, stimulated by hypoxia and transfected with adenovirus expressing miR-98-5p. The exosomes were extracted from BMSCs and named as BMSC-exos. The rat MI/RI models were established by ligation of left anterior descending artery and were respectively injected. Then, hemodynamic indices, myocardial enzymes, oxidative stress factors, inflammatory factors, macrophage infiltration and infarct size in these rats were determined. Expression of miR-98-5p, toll-like receptor 4 (TLR4) and the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway-related proteins was assessed. The target relation between miR-98-5p and TLR4 was confirmed by bioinformatic method and dual luciferase report gene assay. RESULTS: MiR-98-5p was downregulated, TLR4 was upregulated and the PI3K/Akt signaling pathway was inactivated in MI/RI rat myocardial tissues. Exosomal miR-98-5p from hypoxic BMSCs promoted cardiac function and suppressed myocardial enzyme levels, oxidative stress, inflammation response, macrophage infiltration and infarct size in I/R myocardial tissues. Moreover, TRL4 was targeted by miR-98-5p and miR-98-5p activated PI3K/Akt signaling pathway. CONCLUSION: Hypoxia-induced BMSC-exos elevated miR-98-5p to protect against MI/RI. This study may be helpful for treatment of MI/RI.

Inter-provincial sectoral embodied CO2 net-transfer analysis in China based on hypothetical extraction method and complex network analysis.

To address the CO2 emissions issue, China promised to increase its nationally determined contributions, trying to reach a CO2 emissions peak by 2030. For optimizing emission reduction policies, it is important to clarify the CO2 linkage structure and transfer characteristics. Previous research mainly focused on the calculation and comparison of CO2 linkage at the national level or the regional level and lacked inter-provincial sector-sector transfer analysis. This study uses hypothetical extraction method (HEM) to calculate the inter-provincial sectoral linkages of embodied CO2 in 2012 and 2015, providing a new perspective for sectoral CO2 linkage studies in China. We use net transfer to reveal the impact of provincial trade on the embodied CO2 emissions, and identify key CO2 emitter sectors. Combined with complex networks, we describe the clustering feature visualized and identify the transfer media sectors. The results are as follows: (1) the key sectors with large linkage are mainly the heavy industries located in North China. The electricity industry has the largest net CO2 outflow as the energy supplier, whereas the construction industry has the largest net inflow as the driving sector. (2) The CO2 transfer networks present closely connected and spatial clustering features, reflecting the embodied CO2 linkage between geographically adjacent sectors closer. (3) The important media sectors are mostly located in northwest China with small industrial scale and linkage degrees, such as the transport equipment industry in Shanxi. Emission reduction policies should be overall planned and tailored to local conditions. Consequently, possible policy implications of the results are discussed, which could provide additional insights for CO2 mitigation.

Gene Expression Profile Reveals Hematopoietic-Related Molecule Changes in Response to Hypoxic Exposure.

The Qing-Tibet Plateau is characterized by low oxygen pressure, which is an important biomedical and ecological stressor. However, the variation in gene expression during periods of stay on the plateau has not been well studied. We recruited eight volunteers to stay on the plateau for 3, 7, and 30 days. Human Clariom D arrays were used to measure transcriptome changes in the mRNA expression profiles in these volunteers' blood. Analysis of variance (ANOVA) indicated that 699 genes were significantly differentially expressed in response to entering the plateau during hypoxic exposure. The genes with changes in transcript abundance were involved in the terms phosphoprotein, acetylation, protein binding, and protein transport. Furthermore, numerous genes involved in hematopoietic functions, including erythropoiesis and immunoregulation, were differentially expressed in response to hypoxia. This phenomenon may be one of reasons why the majority of people entering the plateau do not have excessive erythrocyte proliferation and are susceptible to infection.

Genetic changes in the EPAS1 gene between Tibetan and Han ethnic groups and adaptation to the plateau hypoxic environment.

In the Chinese Han population, prolonged exposure to hypoxic conditions can promote compensatory erythropoiesis which improves hypoxemia. However, Tibetans have developed unique phenotypes, such as downregulation of the hypoxia-inducible factor pathway through EPAS1 gene mutation, thus the mechanism of adaption of the Han population should be further studied. The results indicated that, under plateau hypoxic conditions, the plains population was able to acclimate rapidly to hypoxia through increasing EPAS1 mRNA expression and changing the hemoglobin conformation. Furthermore, the mutant genotype frequencies of the rs13419896, rs1868092 and rs4953354 loci in the EPAS1 gene were significantly higher in the Tibetan population than in the plains population. The EPAS1 gene expression level was lowest in the Han population carrying the A-A homozygous mutant of the rs13419896 locus but that it increased rapidly after these individuals entered the plateau. At this time, the hemoglobin content was lower in the homozygous mutant Han group than in the wild-type and heterozygous mutant populations, and the viscosity of blood was reduced in populations carrying the A-A haplotypes in rs13419896 and rs1868092 Among Tibetans, the group carrying homozygous mutations of the three SNPs also had lower hemoglobin concentrations than the wild-type. The Raman spectroscopy results showed that exposure of the Tibetan and Han population to hypoxic conditions changed the spatial conformation of hemoglobin and its binding ability to oxygen. The Tibetan population has mainly adapted to the plateau through genetic mutations, whereas some individuals adapt through changes in hemoglobin structure and function.

Health damage assessment of particulate matter pollution in Jing-Jin-Ji region of China.

Jing-Jin-Ji is the largest and most dynamic economic region in northern China, and its air pollution has attracted much public attention. Scientific evaluation of health losses caused by air pollution can provide decision-making basis for formulation and improvement of pollution reduction policies in the Jing-Jin-Ji region. This paper estimated the adverse effects of particulate matter pollution on health in the Jing-Jin-Ji region in 2016 by using logarithmic linear exposure-response function, and monetized the health effects by adjusting human capital method and disease cost method. The results show non-ignorable health hazards and economic impacts caused by atmospheric particulate pollution. The economic losses relevant to health hazards by PM2.5 in the Jing-Jin-Ji region are 122.40 billion yuan, and those relevant to PM10 are 118.34 billion yuan, accounting for 1.62% and 1.56% of the region's GDP, respectively. Similar evaluations previously conducted in other countries yielded figures within the same order of magnitude. Considering the difference in economic losses per unit among disease types, the economic losses caused by air pollution in the Jing-Jin-Ji region mainly come from premature deaths. Infants and elderly people are the main victims of particulate matter. Affected by population, pollutant concentration, industrial structure, and other factors, the economic losses of particulate matter pollution in Beijing, Tianjin, Shijiazhuang, Tangshan, and Baoding are large. In order to reduce health hazards and economic impacts caused by particulate matter pollution, this paper put forward to guide the urban population diversion, reduce the outgoing frequency of susceptible groups such as infants and the elderly in haze weather, adopt high-efficiency particulate matter air purifier indoors, and develop public transportation to reduce motor vehicle exhaust emissions. In Tianjin and Hebei, promoting cleaner production in industries such as steel and cement and reducing coal use in the power industry are also suggested.

Stability of plasma proteins and factors in Chinese universal pooled plasma.

OBJECTIVE: This study aimed to determine the precision dose of Chinese universal pooled plasma (CUPP) developed by our laboratory, and the stability of plasma proteins and factors. METHODS: A total of 100 single fresh-frozen plasma (FFP) units were selected to test plasma proteins, including total protein, albumin, fibrinogen, factor V, factor VIII, antithrombin-III, and protein C. Different pooling protocols with 20, 40, 60, 80, and 100 units were used to optimize the number of pooled units. The pooled plasma was then used to further evaluate the optimal storage conditions and duration at 22°C, 4°C, and -20°C. RESULTS: There were considerable differences in plasma protein levels among single units of FFP. After different pooling protocols, the mean value of plasma proteins did not significantly change. However, with a larger number of pooled samples, plasma proteins were more stable with a smaller standard deviation. Acceptable storage for CUPP was achieved with storage for 1 day at 22°C, 4 days at 4°C, and 3 months at -20°C. CONCLUSION: A uniform level of plasma proteins and factors in CUPP appears to support establishment of a precise dose of plasma.

Different Erythrocyte MicroRNA Profiles in Low- and High-Altitude Individuals.

Background: The number of red blood cells (RBCs) increases significantly in response to high-altitude hypoxic environments, and the RBC microRNA (miRNA) expression pattern is similar to that in whole blood. Studies have shown that miRNA in plasma can act as a circulating hypoxia-associated marker, but the effect of a high-altitude hypoxic environment on RBC-derived miRNAs has not yet been reported. Methods: Blood samples were collected from 20 Han Chinese individuals residing at 500 m (Sichuan Han), 10 migrant Han Chinese citizens residing at 3,658 m (Tibet Han) and 12 native Tibetans, and RBC indices measurements and miRNA sequencing analyses were performed for the three sample groups. The levels of some markedly altered miRNAs at high altitude were subsequently measured from 5 randomly selected samples of each group by real-time PCR. Bioinformatic analyses was performed to determine the potential target genes of selected hypoxia-associated miRNAs. Results: Marked changes of several RBC indices were observed among the Tibet Han population, the Tibetan population and the Sichuan Han population. A total of 516 miRNAs derived from RBCs were initially identified by miRNA sequencing in the three sample groups. Compared with the Sichuan Han population, 49 miRNAs were differentially expressed in the Tibet Han population (17 upregulated and 32 downregulated). 12 upregulated and 21 downregulated miRNAs were observed in the Tibetan population compared with the Sichuan Han population. A total of 40 RBC miRNAs were differentially expressed in the Tibetan population (15 upregulated and 25 downregulated) compared with the Tibet Han population. Two significantly altered miRNAs with the highest expression levels (miRNA-144-5p and miR-30b-5p) were selected for real-time PCR analysis, and the results were consistent with those of miRNA sequencing. Furthermore, bioinformatic analyses showed that some potential target genes of miR-144-5p and miR-30b-5p are involved in the erythroid- hypoxia-, and nitric oxide (NO)-related signaling pathways in response to hypoxia. Conclusion: Our findings provide clear evidence, for the first time, that a high-altitude hypoxic environment significantly affects human RBC miRNA profiles.

Induction of Pluripotent Stem Cell-Derived Cardiomyocyte Toxicity by Supernatant of Long Term-Stored Red Blood Cells in Vitro.

BACKGROUND/AIMS: Preserved red blood cells (RBCs) in vitro undergo a series of morphological, functional and metabolic changes during storage. RBC metabolites accumulate over time during storage, the toxicity of the supernatants of RBCs (SSRBCs) on tissue cells is largely unknown. Here, we aimed to study cardiomyocyte toxicity by supernatant of long term-stored RBCs in vitro and to discover elements involved in the mechanism. METHODS: Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) and real-time cell analyzing (RTCA), we analyzed the cardiotoxicity of d0, d14 and d35 SSRBCs. To analyze the cardiotoxicity of potassium (K) and lactic acid (LA) in SSRBCs, solutions containing the same concentrations of K and LA were respectively prepared and co-cultured with hiPS-CMs. Immunofluorescence and Gene Expression Array of hiPS-CMs were performed to evaluate the effects of d35 K and d35 SSRBCs. RESULTS: The beating of hiPS-CM was stopped by d14, d35 SSRBCs, or d35 K solution. Beating resumed within 48 hours in the presence of d14 SSRBC or d35 K but not d35 SSRBC; d0, d14 and d35 LA solution had no effect on beating patterns. At 48h after treatment, the immunofluorescence results showed that the integrity of the filament and sarcomere were intact. Gene Expression Array results found 14 differentially expressed genes which were likely to play an important role in the cytotoxic effect. CONCLUSION: Our results demonstrated cardiomyocyte toxicity by long term-stored SSRBCs in vitro. Besides high K-induced cardiotoxicity, there must be other unknown components in long term-stored SSRBCs that are cytotoxic to hiPS-CMs.

Effects of individualized exercise program on physical function, psychological dimensions, and health-related quality of life in patients with chronic kidney disease: A randomized controlled trial in China.

The aim of this study was to examine the effects of a 12-week home-based exercise program on physical function, psychological dimensions, and health-related quality of life for patients with chronic kidney disease. Ninety eligible patients were enrolled and randomly separated into the exercise group and the control group from November 2015 to May 2016. The exercise group received an individualized exercise program while the control group received only usual care and continued primary lifestyle. Physical function was measured using 6-minute walk test and 10 repetitions of the sit-to-stand test while psychological dimensions were assessed by the Hospital Anxiety and Depression scale and the Self-Efficacy for Exercise scale. Quality of life was evaluated by a disease-specific instrument, the Kidney Disease Quality of Life scale. The differences between the exercise group and the control group were statistically significant for 6-minute walk distance, the time to complete 10 repetitions of the sit-to-stand test, self-efficacy for exercise, anxiety and depression, and all domains of health-related quality of life after a 12-week exercise. This study suggests that home-based individualized exercise program is an effective and feasible way of improving physical function, psychological stress, and health-related quality of life for early stage of chronic kidney disease patients.

Decomposition analysis of energy-related carbon emissions from the transportation sector in Beijing.

In the process of rapid development and urbanization in Beijing, identifying the potential factors of carbon emissions in the transportation sector is an important prerequisite to controlling carbon emissions. Based on the expanded Kaya identity, we built a multivariate generalized Fisher index (GFI) decomposition model to measure the influence of the energy structure, energy intensity, output value of per unit traffic turnover, transportation intensity, economic growth and population size on carbon emissions from 1995 to 2012 in the transportation sector of Beijing. Compared to most methods used in previous studies, the GFI model possesses the advantage of eliminating decomposition residuals, which enables it to display better decomposition characteristics (Ang et al., 2004). The results show: (i) The primary positive drivers of carbon emissions in the transportation sector include the economic growth, energy intensity and population size. The cumulative contribution of economic growth to transportation carbon emissions reaches 334.5%. (ii) The negative drivers are the transportation intensity and energy structure, while the transportation intensity is the main factor that restrains transportation carbon emissions. The energy structure displays a certain inhibition effect, but its inhibition is not obvious. (iii) The contribution rate of the output value of per unit traffic turnover on transportation carbon emissions appears as a flat "M". To suppress the growth of carbon emissions in transportation further, the government of Beijing should take the measures of promoting the development of new energy vehicles, limiting private vehicles' increase and promoting public transportation, evacuating non-core functions of Beijing and continuingly controlling population size.

[Study of chin morphology in Angle Class II division 2 malocclusion after non-extraction orthodontic treatment].

PURPOSE: To investigate the effect of non-extraction orthodontic treatment on the changes of chin morphology in Angle Class II division 2 malocclusion patients without tooth extractions. METHODS: A total of 20 patients with Class II division 2 malocclusion were treated with MBT straight wire appliance. Cephalometrics analysis was performed before and after treatment. The chin morphology, the position of the incisors and the profile before and after orthodontic treatment were included in the analysis. The data was analysed statistically with PASW statistics18. RESULTS: With the correction of the lingually inclined maxillary incisors, the mandibular plane moved anteroinferiorly and the anterior lower facial height increased.The chin moved forward, with introcession, the depth of the mentolabial sulcus and the chin projection decreased. Upper lip-E line and lower lip-E line became normal or close to normal. All cases showed a better improvement of the profile after treatment(P<0.05). CONCLUSIONS: In Class II division 2 malocclusion patients, after the lingually inclined maxillary incisors were corrected,the chin position could be orthodontically changed and soft tissue profile will be more esthetical.

[Effect of bioactive glass filling defective alveolar bone on tooth movement].

OBJECTIVE: To observe the movement of rat's tooth in the area of defective alveolar bone filled with bioglass in comparison with contralateral tooth. METHODS: Forty female Wistar rats were selected. Defects in alveolar bones were created and filled with bioglass. Orthodontic appliances were fixed to mesially guide the maxillary first molars. RESULTS: The rats' teeth were mesially moved in the area filled with bioglass. There were no significant differences between two sides in movement distance of the first molars and in thickness of periodontal tissues with paired t-test (P > 0.05). CONCLUSIONS: The rat's tooth can be mesially moved in the area filled with bioglass.

[The discrepancy between ICP and MCP caused by orthodontic treatment and its quantitative assessment to the effect of later orthodontic treatment.].

PURPOSE: To investigate the discrepancy between ICP and MCP caused by orthodontic treatment. to evaluate the treatment effect of the malocclusion with later orthodontic treatment. METHODS: Nineteen cases were selected and treated with preadjusted appliance and combination headgear appliance.Pre- and post- treatment celphalometric radiographs were analyzed. RESULTS: Discrepancy between ICP and MCP may be resulted from improper design and operation of orthodontists and poor cooperation of patients; By preadjusted appliance and combination headgear appliance,upper dental arch was moved distally; Molar relationship was changed into Class I by bodily movement; A harmonization between ICP and MCP was rehabilitated. CONCLUSIONS: The discrepancy between ICP and MCP should be minded; Preadjusted appliance and combination headgear appliance were effective in the correction of the discrepancy between ICP and MCP.