Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of miR-193a-3p protects human umbilical vein endothelial cells against intermittent hypoxia-induced endothelial injury by targeting FAIM2

Objective: The functions and molecular regulatory mechanisms of miR-193a-3p in cardiac injury induced by obstructive sleep apnea (OSA) are poorly understood. This study aimed to explore the role of miR-193a-3p in intermittent hypoxia(IH)-induced human umbilical vein endothelial cells (HUVECs) injury. Results: In this study, we found that IH significantly decreased viability but enhanced cell apoptosis. Concurrently, the miR-193a-3p expression level was increased in HUVECs after IH. Subsequent experiments showed that IH-induced injury was ameliorated through miR-193a-3p silence. Fas apoptotic inhibitory molecule 2 (FAIM2) was predicted by bioinformatics analysis and further identified as a direct target gene of miR-193a-3p. Interestingly, the effect of miR-193a-3p inhibition under IH could be reversed by down-regulating FAIM2 expression. Conclusion: In conclusion, our study first revealed that miR-193a-3p inhibition could protect HUVECs against intermittent hypoxia-induced damage by negatively regulating FAIM2. These findings could advance our understanding of the underlying mechanisms for OSA-related cardiac injury. Methods: We exposed HUVECs to IH condition; the expression levels of miR-193a-3p were detected by RT-qPCR. Cell viability, and the expressions of apoptosis-associated proteins were examined via CCK-8, and western blotting, respectively. Target genes of miR-193a-3p were confirmed by dual-luciferase reporter assay.
ERK1/2-PPARγ pathway is involved in Chlamydia pneumonia-induced human umbilical vein endothelial cell apoptosis through increased LOX-1 expression

Abstract Chlamydia pneumonia (C.pn) is a common respiratory pathogen that is involved in human cardiovascular diseases and promotes the development of atherosclerosis in hyperlipidemic animal models. C.pn reportedly up-regulated lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells. Recently, the anti-atherosclerotic activity of peroxisome proliferator-activated receptor γ (PPARγ) has been documented. In the present study, we investigated the effect of C.pn on LOX-1 expression in human umbilical vein endothelial cells (HUVECs) and identified the involvement of the PPARγ signaling pathway therein. The results showed that C.pn increased the expression of LOX-1 in HUVECs in a dose- and time-dependent manner. C.pn-induced up-regulation of LOX-1 was mediated by ERK1/2, whereas p38 MAPK and JNK had no effect on this process. C.pn induced apoptosis, inhibited cell proliferation, and decreased the expression PPARγ in HUVECs. Additionally, LOX-1 activity and cell injury caused by C.pn through activation of ERK1/2 was completely inhibited by rosiglitazone, a PPARγ agonist. In conclusion, we inferred that activation of PPARγ in HUVECs suppressed C.pn-induced LOX-1 expression and cell damage by inhibiting ERK1/2 signaling.
Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum

Background: House dust contains many organic contaminants that can compete with the thyroid hormone (TH) thyroxine (T4) for binding to transthyretin (TTR). How these contaminants work together at levels found in humans and how displacement from TTR in vitro relates to in vivo T4-TTR binding is unknown. Objectives: Our aims were to determine the TTR-binding potency for contaminant mixtures as found in house dust, maternal serum, and infant serum; to study whether the TTR-binding potency of the mixtures follows the principle of concentration addition; and to extrapolate the in vitro TTR-binding potency to in vivo inhibition levels of T4-TTR binding in maternal and infant serum. Methods: Twenty-five contaminants were tested for their in vitro capacity to compete for TTR-binding with a fluorescent FITC-T4 probe. Three mixtures were reconstituted proportionally to median concentrations for these chemicals in house dust, maternal serum, or infant serum from Nordic countries. Measured concentration–response curves were compared with concentration–response curves predicted by concentration addition. For each reconstituted serum mixture, its inhibitor–TTR dissociation constant (Ki) was used to estimate inhibition levels of T4-TTR binding in human blood. Results: The TTR-binding potency of the mixtures was well predicted by concentration addition. The ∼20% inhibition in FITC-T4 binding observed for the mixtures reflecting median concentrations in maternal and infant serum was extrapolated to 1.3% inhibition of T4-TTR binding in maternal and 1.5% in infant blood. For nontested mixtures reflecting high-end serum concentrations, these estimates were 6.2% and 4.9%, respectively. Discussion: The relatively low estimated inhibition levels at median exposure levels may explain why no relationship between exposure to TTR-binding compounds and circulating T4 levels in humans has been reported, so far. We hypothesize, however, that 1.3% inhibition of T4-TTR binding may ultimately be decisive for reaching a status of maternal hypothyroidism or hypothyroxinemia associated with impaired neurodevelopment in children. https://doi.org/10.1289/EHP5911
Lemur catta in small forest fragments: Which variables best predict population viability?

Habitat fragmentation is an increasingly serious issue affecting primates in most regions where they are found today. Populations of Lemur catta (ring‐tailed lemur) in Madagascar's south‐central region are increasingly restricted to small, isolated forest fragments, surrounded by grasslands or small‐scale agriculture. Our aim was to evaluate the potential for population viability of L. catta in nine forest fragments of varying sizes (2–46 ha, population range: 6–210 animals) in south‐central Madagascar, using a set of comparative, quantitative ecological measures. We used Poisson regression models with a log link function to examine the effects of fragment size, within‐fragment food availability, and abundance of matrix resources (food and water sources) on L. catta population sizes and juvenile recruitment. We found a strong association between overall population size and (a) fragment size and (b) abundance of key food resources Melia azedarach and Ficus spp. (per 100 m along transect lines). Juvenile recruitment was also associated with fragment size and abundance of the two above‐mentioned food resources. When the largest population, an outlier, was removed from the analysis, again, the model containing fragment size and abundance of M. azedarach and Ficus spp. was the best fitting, but the model that best predicted juvenile recruitment contained only fragment size. While our results are useful for predicting population presence and possible persistence in these fragments, both the potential for male dispersal and the extent of human disturbance within most fragments play crucial roles regarding the likelihood of long‐term L. catta survival. While seven of the nine fragments were reasonably protected from human disturbance, only three offered the strong potential for male dispersal, thus the long‐term viability of many of these populations is highly uncertain.
Tryptophan residue 32 in human Cu-Zn superoxide dismutase modulates prion-like propagation and strain selection

Mutations in Cu/Zn superoxide dismutase 1 (SOD1) associated with familial amyotrophic lateral sclerosis cause the protein to aggregate via a prion-like process in which soluble molecules are recruited to aggregates by conformational templating. These misfolded SOD1 proteins can propagate aggregation-inducing conformations across cellular membranes. Prior studies demonstrated that mutation of a Trp (W) residue at position 32 to Ser (S) suppresses the propagation of misfolded conformations between cells, whereas other studies have shown that mutation of Trp 32 to Phe (F), or Cys 111 to Ser, can act in cis to attenuate aggregation of mutant SOD1. By expressing mutant SOD1 fused with yellow fluorescent protein (YFP), we compared the relative ability of these mutations to modulate the formation of inclusions by ALS-mutant SOD1 (G93A and G85R). Only mutation of Trp 32 to Ser persistently reduced the formation of the amorphous inclusions that form in these cells, consistent with the idea that a Ser at position 32 inhibits templated propagation of aggregation prone conformations. To further test this idea, we produced aggregated fibrils of recombinant SOD1-W32S in vitro and injected them into the spinal cords of newborn mice expressing G85R-SOD1: YFP. The injected mice developed an earlier onset paralysis with a frequency similar to mice injected with WT SOD1 fibrils, generating a strain of misfolded SOD1 that produced highly fibrillar inclusion pathology. These findings suggest that the effect of Trp 32 in modulating the propagation of misfolded SOD1 conformations may be dependent upon the “strain” of the conformer that is propagating.
Effect of puerarin on action potential and sodium channel activation in human hypertrophic cardiomyocytes

Abstract Objective: To study the effect of puerarin on electrophysiology using a hypertrophic cardiomyocyte (HC) model. Materials and methods: Human urine epithelial cells were used to generate the HC model (hiPSC-CM). Cardiomyocyte hypertrophy was induced by applying 10 nM endothelin-1 (ET-1). Effects of puerarin pre-treatment (PPr) and post-treatment (PPo) on action potential, sodium current (INa) activation and inactivation, and recovery following INa inactivation were tested using patch clamp electrophysiology. Results: Depolarization to repolarization 50% time (APD50) and repolarization 30% time (APD30) were significantly prolonged in the PPo and PPr groups compared with the controls. However, there were no significant differences in the action potential depolarization amplitude (APA) or the maximum depolarization velocity (Vmax) in phase 0. The PPr group had a slightly shortened APD90, and an extended APD50 and APD30, but did not exhibit any significant changes in stage A of APA and Vmax. The PPo group did not exhibit any significant changes in INa, while 12 h of PPr improved INa. However, puerarin did not significantly affect the activation, inactivation, or recovery of the sodium channel. Conclusions: Cardiomyocyte hypertrophy significantly decreased the Vmax of the action potential and the peak density of INa. PPr inhibited the decrease in Vmax and increased the peak density of INa. Thus, puerarin could be used to stabilize the electrophysiological properties of hypertrophic cardiomyocytes and reduce arrhythmias.
Lower‐than‐expected CH4 emissions from rice paddies with rising CO2 concentrations

Elevated atmospheric CO2 (eCO2) generally increases carbon input in rice paddy soils and stimulates the growth of methane‐producing microorganisms. Therefore, eCO2 is widely expected to increase methane (CH4) emissions from rice agriculture, a major source of anthropogenic CH4. Agricultural practices strongly affect CH4 emissions from rice paddies as well, but whether these practices modulate effects of eCO2 is unclear. Here we show, by combining a series of experiments and meta‐analyses, that whereas eCO2 strongly increased CH4 emissions from paddies without straw incorporation, it tended to reduce CH4 emissions from paddy soils with straw incorporation. Our experiments also identified the microbial processes underlying these results: eCO2 increased methane‐consuming microorganisms more strongly in soils with straw incorporation than in soils without straw, with the opposite pattern for methane‐producing microorganisms. Accounting for the interaction between CO2 and straw management, we estimate that eCO2 increases global CH4 emissions from rice paddies by 3.7%, an order of magnitude lower than previous estimates. Our results suggest that the effect of eCO2 on CH4 emissions from rice paddies is smaller than previously thought and underline the need for judicious agricultural management to curb future CH4 emissions.
Development of the Continuous Number Identification Test (CNIT): feasibility of dynamic assessment of speech intelligibility

Abstract Objective: The present study was motivated by a need for a speech intelligibility test capable of indexing dynamic changes in the environment and adaptive processing in hearing aids. The Continuous Number Identification Test (CNIT) was developed to meet these aims. Design: From one location in the free field, speech was presented in noise (∼2 words/s) with a 100-ms inter-word interval. On average, every fourth word was a target digit and all other words were monosyllabic words. Non-numeric words had a fixed presentation level such that the dominant signal-to-noise-ratio (SNR) was held at +6 dB SNR relative to background maskers. To prevent ceiling effects, however, targets were presented at a user-specific SNR, determined by an initial adaptive-tracking procedure that estimated the 79.4% speech reception threshold. Study sample: Ten normal-hearing listeners participated. Results: The CNIT showed comparable psychometric qualities of other established speech tests for long time scales (Exp. 1). Target-location changes did not affect performance on the CNIT (Exp. 2), but the test did show high temporal resolution in assessing sudden changes to SNR (Exp. 3). Conclusions: The CNIT is highly customisable, and the initial experiments tested feasibility of its primary features which set it apart from currently available speech-in-noise tests.
Short Physical Performance Battery: What Does Each Sub-Test Measure in Patients with Chronic Obstructive Pulmonary Disease?

Objective To identify phenotypic factors associated with the Short Physical Performance Battery (SPPB) and its individual sub-tests: standing balance, 4‑meter gait speed (4mGS) and 5-repetition sit-to-stand (5STS). Methods The Evaluation of the Role of Inflammation in non-pulmonary disease manifestations in Chronic Airways disease (ERICA) study recruited adult participants with stable chronic obstructive pulmonary disease (COPD). Proportional odds models identified factors associated with the SPPB, and a principal component analysis (PCA) evaluated how much SPPB variance was explainable by each of its 3 sub-tests. Results Of 729 enrolled participants, 717 (60% male, mean age 67 years) had full SPPB data. Overall, 76% of patients had some evidence of functional limitations (SPPB total score < 12). Scores < 4 were observed in 71%, 31%, and 22% of participants for the 5STS, 4mGS, and balance sub-tests, respectively. A longer 6-minute walk test and greater quadriceps maximal voluntary contraction decreased the odds of being in a lower score category for SPPB total score and for all 3 sub-tests. Aging, self-reported hypertension and higher dyspnea increased the odds, and being married decreased the odds of being in a lower category for total score. All sub-tests contributed equally to total score. Conclusion Each of the 3 sub-tests contributed independent information to the SPPB, demonstrating their usefulness for assessing COPD when considered together rather than individually. The 5STS sub-test had the greatest variation in scores and may thus have the best discriminatory power for clinical COPD studies of lower limb performance where only one SPPB test is feasible.
Phospholipid profiling enables to discriminate tumor- and non-tumor-derived human colon epithelial cells: Phospholipidome similarities and differences in colon cancer cell lines and in patient-derived cell samples

Identification of changes of phospholipid (PL) composition occurring during colorectal cancer (CRC) development may help us to better understand their roles in CRC cells. Here, we used LC-MS/MS-based PL profiling of cell lines derived from normal colon mucosa, or isolated at distinct stages of CRC development, in order to study alterations of PL species potentially linked with cell transformation. We found that a detailed evaluation of phosphatidylinositol (PI) and phosphatidylserine (PS) classes allowed us to cluster the studied epithelial cell lines according to their origin: i) cells originally derived from normal colon tissue (NCM460, FHC); ii) cell lines derived from colon adenoma or less advanced differentiating adenocarcinoma cells (AA/C1, HT-29); or, iii) cells obtained by in vitro transformation of adenoma cells and advanced colon adenocarcinoma cells (HCT-116, AA/C1/SB10, SW480, SW620). Although we tentatively identified several PS and PI species contributing to cell line clustering, full PI and PS profiles appeared to be a key to the successful cell line discrimination. In parallel, we compared PL composition of primary epithelial (EpCAM-positive) cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients, with PL profiles of cell lines derived from normal colon mucosa (NCM460) and from colon adenocarcinoma (HCT-116, SW480) cells, respectively. In general, higher total levels of all PL classes were observed in tumor cells. The overall PL profiles of the cell lines, when compared with the respective patient-derived cells, exhibited similarities. Nevertheless, there were also some notable differences in levels of individual PL species. This indicated that epithelial cell lines, derived either from normal colon tissue or from CRC cells, could be employed as models for functional lipidomic analyses of colon cells, albeit with some caution. The biological significance of the observed PL deregulation, or their potential links with specific CRC stages, deserve further investigation.
Physical activity and heart rate monitoring in Fontan patients – Should we recommend activities in higher intensities?

Objective Exercise capacity is impaired in Fontan palliated patients. The change in daily activity behaviour with an increase in sedentary lifestyle results in low physical activity levels. This might have a greater impact on patients with chronic heart disease in contrast to healthy controls. For a better understanding, we compared data from cardiopulmonary exercise testing (CPET) with heart rates and physical activity in daily life. Methods 21 Fontan patients and 20 age, sex and BMI matched controls underwent CPET and 5 days of daily life activity tracking with a triaxial accelerometer (wGT3x-BT, Actigraph) including heart rate monitoring with an optical heart rate sensor. Results 27% of our Fontan teenagers and 71% of the Fontan adults reached the specific WHO recommendations for moderate to vigorous physical activity (MVPA) during everyday life (EDL), without differences to controls. There was a strong correlation between MVPA and V˙O2peak for all Fontan patients (p = 0.0035, Pearson r = 0.788). Daily MVPA correlated to peak oxygen uptake and lactate production. Up to workloads of 2 W/kg and in daily life heart rates in Fontan patients were similar to controls. Conclusions Daily MVPA is alarmingly low without any differences between Fontan patients and controls. Heart rate behaviour was similar and does not seem to be a limiting factor for physical activity in daily life. Higher intensity activities should be implemented regularly in EDL for Fontan patients. Proof is needed as to whether sports in moderate or possibly even in vigorous activity (e.g. high-intensity interval training) improve exercise capacity the most.
The effects of lauric acid on IPEC-J2 cell differentiation, proliferation, and death.

BACKGROUND Lauric acid (LA) has antimicrobial effects and the potential to replace antibiotics in feeds to prevent postweaning diarrhea and increase overall swine productivity. The effects of lauric acid on the intestinal epithelial cells remain unclear. MATERIALS AND METHODS This study investigates the effects of LA on pig intestinal epithelial cell line (IPEC-J2) differentiation, proliferation, and death and explores its underlying mechanisms. It was found that 0.25-0.1 mM LA promoted the IPEC-J2 cell differentiation. At 1 mM or higher concentrations, it induced IPEC-J2 cell viability decreases, lipid accumulation, cell proliferation inhibition, and cell apoptosis. The cell death induced did not depended on caspase pathways. RESULTS The data demonstrated that LA induced the IPEC-J2 cell autophagy and impaired autophagy flux. And autophagy plays a role in protecting against LA induced-cell death. p38 MAPK inhibitor SB202190 attenuated LA-reduced IPEC-J2 cell viability. This associated with an increase autophagy level and decrease in lipid accumulations and FABPI levels. CONCLUSION In summary, LA promoted the IPEC-J2 cell apoptosis depended on the p38 MAPK pathways and may involve autophagy and TG metabolism regulation.
Assessment irradiation effects on different development stages of Callosobruchus maculatus and on chemical, physical and microbiological quality of cowpea seeds

Abstract Irradiation is a physical, environmentally friendly treatment which does not leave any residues in the product. It is increasingly used as an alternative to methyl bromide and other chemical fumigants for disinfestation of insect pest in stored grains. In this research, we try to evaluate the effect of low gamma irradiation doses in the range of 50–1200 Gy on the different stages of Callosobruchus maculatus. It was found that no adults emerged after irradiation of eggs at 450 Gy. No emerging adults (F1 generation) have been shown when larvae or pupae were exposed to 650 Gy. Also, no emerging adult has been shown from the parental C. maculatus adults irradiated with 650 Gy. When suppression of F1 generation was used for the measuring effective irradiation dose and phytosanitary efficacy, 650 Gy was required for disinfestation of cowpea seed weevils. The irradiation dose level of 650 Gy was used for the large-scale confirmatory tests applied to 27,754 adults of C. maculatus in cowpea seeds resulting in non F1 adults' production with a confidence level of 93.77%. All the physical and chemical characteristics of cowpea seeds were non-significantly (P ≤ 0.05) affected by the irradiation dose of 650 Gy. Meanwhile, this irradiation dose very slightly reduced the microbial load of cowpea seeds. We recommend the generic dose 650 Gy as the phytosanitary irradiation dose for the cowpea seed weevil.
Cabin1 involves in renal tubular epithelial cells mitochondrial dysfunction through SIRT1/p53 pathway

Abstract Background: Angiotensin II (AngII) induced Calcineurin binding protein 1 (Cabin1) protein expression significantly increased during Renal tubular epithelial cells (RTEC) injury. However, the detailed function of Cabin1 protein in RTEC was not characterized well. In this study, we aimed to explore the downstream target of Cabin1 in vitro model. Methods: Rat kidney epithelial cells were cultured and stimulated with AngII. Electron microscopy was performed to observe mitochondrial morphology change. Immunofluorescence staining was detected to observe the distribution of cytoskeleton and Cabin1. Mitochondrial morphology change and protein expression were detected by electrical microscopy and western blot. Results: AngII induced the disruption of cytoskeleton at 24 and 48 h. Western blot analysis showed AngII significantly induced the overexpression of Cabin1. AngII induced a great deal of small, long and irregular mitochondria in RTEC, aspect ratio which reflects the length-to-width ratio of mitochondria remarkably increased at 12 and 24 h. Knocking down Cabin1 aggravated mitochondrial morphological abnormality in AngII treated RTEC. In comparison with control, Cabin1, p53 and cyto C level were significantly increased in AngII treated cells, while SIRT1 level was obviously decreased. Knocked down Cabin1 plus AngII stimulated, SIRT1 was further decreased, while p53 and cyto C were significantly increased. Conclusions: Cabin1 involves in RTEC mitochondrial dysfunction through SIRT1/p53 pathway. Cabin1 may be used as a new marker for the mechanisms of RTEC injury.