The mass and strength of skeletal muscle decline with age, leading to its progressive dysfunction. High-throughput metabolite profiling provides the opportunity to reveal metabolic mechanisms and the ...identification of biomarkers. However, the role of amino acid metabolism in possible sarcopenia remains unclear.
The aim of this study included exploring variations in plasma amino acid concentrations in elderly individuals who have possible sarcopenia and further attempting to characterize a distinctive plasma amino acid profile through targeted metabolomics.
A cross-sectional, correlational research design was used for this study. Thirty possible-sarcopenic elderly participants were recruited (n = 30), as determined by the Asian Working Group for Sarcopenia (AWGS). Meanwhile, a reference group of non-sarcopenic (sex-, age-, and Appendicular Skeletal muscle Mass Index (ASMI)-matched non-sarcopenic controls, n = 36) individuals was included to compare the potential differences in metabolic fingerprint of the plasma amino acids associated with sarcopenia. Both groups were conducted the body composition analysis, physical function examination, and plasma amino acid-targeted metabolomics. The amino acids in plasma were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Also, orthogonal partial least-squares-discriminant analysis (OPLS-DA) was applied to characterize the plasma amino acid profile.
With respect to Handgrip Strength (HGS), the Five-Repetition Chair Stand Test (CS-5), the Six-Minute Walking Test (6MWT), the arm curl, the 30 s-Chair Stand Test (CST), the 2-Minute Step Test (2MST), the Timed Up-and-Go Test (TUGT), there was a decline in skeletal muscle function in the possible-sarcopenic group compared to the non-sarcopenic group. The mean plasma concentrations of arginine, asparagine, phenylalanine, serine, lysine, glutamine, and threonine were significantly lower in the possible sarcopenia group, whereas cirulline, proline, serine, and glutamic acid concentrations were higher. According to the multi-analysis, glutamine, serine, lysine, threonine, and proline were determined as the potential markers that indicated possible sarcopenia.
The findings characterize significantly altered plasma amino acid metabolisms in the elderly with possible sarcopenia, which aids to screening people who are at a high risk of developing condition, and motivating to design new preventive and therapeutic approaches.
An accurate and timely spatialization of electricity consumption is fundamental for energy management and sustainable urban development. While previous research has relied heavily on statistical data ...or moderate-resolution nighttime light data, this study has presented a new spatialization method by combining high-resolution Luojia 1–01 nighttime light and urban functional zoning information. The total electricity consumption volume can be allocated to each land use pixel based on its strong linear relationship with nighttime light. Specifically, urban functional zoning data were connected with the corresponding economic sectors to differentiate the complex relationships between electricity consumption and nighttime light within different zones. The digital number value of every pixel can be multiplied by its corresponding electricity consumption coefficient. A number of comparisons have indicated that the proposed method can more accurately characterize the spatial distribution of electricity consumption. Our results can exhibit much clearer outlines and more detailed internal characteristics. More importantly, urban functional zoning information can be used to distinguish the electricity consumption of various economic sectors at fine scales. The proposed method is expected to capture the spatial characteristics of electricity consumption in a timely and accurate manner. The findings can help local authorities formulate sustainable energy utilization and emission reduction strategies.
Physical activity (PA) has a significant health impact worldwide and has been linked to a lower risk of the common cold.
The aim of this study was to estimate the form of PA among Chinese adults and ...the correlation between PA and number of the common cold in China's eastern, central, and western areas.
A cross-sectional study.
China's eastern, central, and western regions from 30 November 2020 to 30 March 2021.
A total of 1,920 healthy participants, who aged over 18 years old, with Internet access, were enrolled, and then self-reported PA behaviors and number of the common cold were collected.
The authors calculated preference, intensity, frequency, and duration of PA in Chinese based on gender, age, and broad occupational categories and explored the potential effect between these factors and the common cold.
Approximately 20.4% of participants reported not participating in sports regularly. Except for gender, there were significant differences in PA preference and intensity among the remaining individuals (
<0.05). Sixteen common exercises were divided into three intensity levels by the Borg CR10 Scale: low- (5), moderate- (8), and high-intensity exercises (3), and the corresponding intensity, frequency, and duration were computed with significant differences (
<0.05). The most popular workouts are "Brisk walking" and "Running." Age, sex, and occupation had no significant effect on colds (
> 0.05). However, intensity shows a U-shaped dose-response relationship with colds, whereas the frequency and duration have an inverse dose-response relationship (
<0.05). High intensity combined with high frequency increased colds the most. Nevertheless, non-exercise groups always have the most colds in each comparison.
The result may be vulnerable to recall bias.
Intensity showed that U-shape, frequency, and duration showed inverse response to the number of colds last year, but age, sex, and occupation had no significant effects. High intensity and high frequency mixed increased colds the most, regardless of duration.
Rationale: Cerebral ischemia upregulates aquaporin‐4 expression, increases blood‐brain barrier (BBB) permeability, and induces brain edema. Mesenchymal stem cells (MSCs) can repress inflammatory ...cytokines and show great potential for ischemic stroke therapy. However, the effect of MSCs regarding the protection of ischemia‐induced BBB break down is unknown. Objective: We test whether MSCs therapy protects BBB integrity and explore the molecular mechanisms of aquaporin‐4 on BBB integrity. Methods and Results: Two hundred and twenty‐eight adult CD1 male mice underwent 90 minutes transient middle cerebral artery occlusion and received 2 × 105 MSCs intracranial transplantation. The neurological severity score was improved and both ischemia‐induced brain edema and BBB leakage were reduced in MSC‐treated mice. MSCs therapy reduced astrocyte apoptosis and inhibited ischemia‐induced aquaporin‐4 upregulation. In addition, small‐interfering RNA knockdown of aquaporin‐4 after cerebral ischemia effectively reduced aquaporin‐4 expression, brain edema, BBB leakage, and astrocyte apoptosis. Conditional medium from lipopolysaccharide (LPS)‐activated microglia enhanced aquaporin‐4 expression, p38 and JNK phosphorylation, and apoptosis of cultured astrocytes. MSC treatment reduced the expression of inflammatory cytokines in LPS‐activated microglia, and subsequently reduced aquaporin‐4 expression and apoptosis of astrocytes. Knockdown of aquaporin‐4 in cultured astrocytes also reduced apoptosis. Treatment with p38 and JNK inhibitors showed that p38, but not the JNK signaling pathway, was responsible for the aquaporin‐4 upregulation. Conclusion: MSCs protected BBB integrity by reducing the apoptosis of astrocytes after ischemic attack, which was due to the attenuation of inflammatory response and downregulation of aquaporin‐4 expression via p38 signaling pathway. Stem Cells 2014;32:3150–3162
Regional studies have found significant agglomeration effects of education development on economic growth. Regional favouritism is potentially closely related to public investment in education, ...further impacting regional growth. This paper provides significant empirical evidence on the potential impact of favouritism on education development in the Chinese context. Using data for 282 Chinese cities from 1996 to 2016 with treatment for endogeneity (Lewbel two-stage least squares estimator), the results provide evidence that Chinese provincial political leaders favour their birthplaces' education resource development, and that the effect is larger for within-provincial impact and higher tier cities ranked by income.
The development of big data technologies, which have been applied extensively in various areas, has become one of the key factors affecting modern society, especially in the virtual reality ...environment. This paper provides a comprehensive survey of the recent developments in big data technologies, and their applications to virtual reality worlds, such as the Metaverse, virtual humans, and digital twins. The purpose of this survey was to explore several cutting-edge big data and virtual human modelling technologies, and to raise the issue of future trends in big data technologies and the Metaverse. This survey investigated the applications of big data technologies in several key areas—including e-health, transportation, and business and finance—and the main technologies adopted in the fast-growing virtual world sector, i.e., the Metaverse.
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•Riverine input might be the dominant Hg source for the nearshore seas.•Apart from direct MeHg discharge, riverine nutrients may affect nearshore MeHg.•Hydro-activities strongly ...influence Hg loads in seas by regulating river inputs.•High Hg flux from the nearshore to open seas was observed based on field surveys.•Non-negligible portions of riverine Hg can travel through the nearshore to open seas.
Rivers are important sources of Hg for adjacent seas, and seafood from nearshore waters is a major source of Hg exposure for humans. There is thus a key scientific concern regarding how much riverine Hg inputs influence Hg loads in nearshore waters as well as how far the impact range can extend from the river to the open sea. In addition, it is important to understand the influence of anthropogenic hydro-facilities and activities on Hg levels in downstream seas. Because of the concise mass exchange pattern between the seas and the previously demonstrated intensive Hg inputs under anthropogenic regulation from the Yellow River, the Bohai and Yellow Seas, which are key fishery and marine breeding areas for China, are an ideal research area for exploring the impacts of riverine Hg on nearshore and adjacent open seas. Field surveys were conducted in eight major rivers and two seas, and 433 water samples were collected. The main Hg input and output terms (rivers, ocean currents, underground discharge, sewage, coastal erosion, atmospheric deposition, surface evasion, sedimentation, and fisheries) were quantified in the Bohai and Yellow Seas. Owing to the high inputs from the Yellow and Yalu Rivers, elevated THg concentrations were found. Apart from direct MeHg discharge, riverine nutrients may also seemingly affect nearshore MeHg. Using mass balance models, we found that the Yellow River (9.8 t) was the dominant Hg source in the Bohai Sea, which accounted for more than half of all contributions, and the Bohai Sea played the role of a secondary source of Hg to the Yellow Sea, with a flux of 3.3 t. Anthropogenic hydro-activities in large rivers could significantly influence Hg outputs and loads in the nearshore and even open seas. This study provides useful information for water resource management applications to reduce potential MeHg risks.
To characterize transcriptomic changes in endothelial cells (ECs) infected by coronaviruses, and stimulated by DAMPs, the expressions of 1311 innate immune regulatomic genes (IGs) were examined in 28 ...EC microarray datasets with 7 monocyte datasets as controls. We made the following findings: The majority of IGs are upregulated in the first 12 hours post-infection (PI), and maintained until 48 hours PI in human microvascular EC infected by middle east respiratory syndrome-coronavirus (MERS-CoV) (an EC model for COVID-19). The expressions of IGs are modulated in 21 human EC transcriptomic datasets by various PAMPs/DAMPs, including LPS, LPC, shear stress, hyperlipidemia and oxLDL. Upregulation of many IGs such as nucleic acid sensors are shared between ECs infected by MERS-CoV and those stimulated by PAMPs and DAMPs. Human heart EC and mouse aortic EC express all four types of coronavirus receptors such as ANPEP, CEACAM1, ACE2, DPP4 and virus entry facilitator TMPRSS2 (heart EC); most of coronavirus replication-transcription protein complexes are expressed in HMEC, which contribute to viremia, thromboembolism, and cardiovascular comorbidities of COVID-19. ECs have novel trained immunity (TI), in which subsequent inflammation is enhanced. Upregulated proinflammatory cytokines such as TNFα, IL6, CSF1 and CSF3 and TI marker IL-32 as well as TI metabolic enzymes and epigenetic enzymes indicate TI function in HMEC infected by MERS-CoV, which may drive cytokine storms. Upregulated CSF1 and CSF3 demonstrate a novel function of ECs in promoting myelopoiesis. Mechanistically, the ER stress and ROS, together with decreased mitochondrial OXPHOS complexes, facilitate a proinflammatory response and TI. Additionally, an increase of the regulators of mitotic catastrophe cell death, apoptosis, ferroptosis, inflammasomes-driven pyroptosis in ECs infected with MERS-CoV and the upregulation of pro-thrombogenic factors increase thromboembolism potential. Finally, NRF2-suppressed ROS regulate innate immune responses, TI, thrombosis, EC inflammation and death. These transcriptomic results provide novel insights on the roles of ECs in coronavirus infections such as COVID-19, cardiovascular diseases (CVD), inflammation, transplantation, autoimmune disease and cancers.
This study investigates the effects of a 12-week brisk walking exercise regimen on motor function improvements in elderly women. Twenty-six elderly women, aged 84.2 ± 3.2 years, participated in a ...12-week brisk walking exercise program. Fitness assessments and blood biomarker analyses (including CHO, HDLC, LDLC, TC) were conducted pre- and post-intervention. Additionally, targeted metabolomics was employed to measure short-chain fatty acids, amino acids, and vitamin metabolites. The intervention led to significant enhancements in participants' flexibility (p < 0.05), lower limb muscle strength (p < 0.01), and cardiorespiratory endurance (p < 0.01), while muscle mass showed no significant changes. Fifteen significant differential metabolites were identified (VIP > 1.0, FC > 1.2 or < 0.8, and p < 0.05), with arginine, ornithine, aspartic acid, glutamine, phenylalanine, tyrosine, and pantothenic acid playing key roles across seven metabolic pathways. A 12-week brisk walking exercise program significantly enhanced flexibility, lower limb muscle strength, and cardiorespiratory endurance among elderly women. These improvements did not extend to muscle mass or upper limb muscle strength. The observed enhancement in exercise capacity may be attributed to improved regulation of neurotransmitters.
Acquired resistance to tyrosine kinase inhibitors (TKIs) is the major obstacle to improve clinical efficacy in cancer patients. The epithelial-stromal interaction in tumor microenvironment influences ...cancer drug response to TKIs. Anlotinib is a novel oral multi-targeted TKI, and has recently been proven to be effective and safe for several tumors. However, if and how the epithelial-stromal interaction in tumor microenvironment affects anlotinib response in gastric cancer (GC) is not known. In this study, we found that anlotinib inhibited GC cells growth by inducing GC cells apoptosis and G2/M phase arrest in a dose- and time-dependent manner. Reactive oxygen species (ROS) mediated anlotinib-induced apoptosis in GC cells, while cancer-associated fibroblasts (CAFs) significantly suppressed anlotinib-induced apoptosis and ROS in GC cells. Increased BDNF that was derived from CAFs activated TrkB-Nrf2 signaling in GC cells, and reduced GC cells response to anlotinib. We identified secreted lactate from GC cells as the key molecule instructing CAFs to produce BDNF in a NF-κB-dependent manner. Additionally, functional targeting BDNF-TrkB pathway with neutralizing antibodies against BDNF and TrkB increased the sensitivity of GC cells towards anlotinib in human patient-derived organoid (PDO) model. Taken together, these results characterize a critical role of the epithelial-stroma interaction mediated by the lactate/BDNF/TrkB signaling in GC anlotinib resistance, and provide a novel option to overcome drug resistance.
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•Anlotinib induced apoptosis through ROS accumulation.•CAFs drive acquired resistance of GC to anlotinib.•TrkB activation by CAFs-derived BDNF confer resistance to anlotinib-induced ROS.•GC cells-secreted lactate induced BDNF expression of CAFs through activating NF-κB.•Blocking BDNF and TrkB reversed CAFs-induced acquired resistance to anlotinib.
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