Iron-doped diesel exhaust early-in-life inhalation-induced cardiopulmonary toxicity in chicken embryo: Roles of ferroptosis and acyl hydrocarbon signaling.

Diesel exhaust (DE) is a major contributor to air pollution. Iron-doping could improve diesel burning efficacy and decrease emission, however, it will also change the composition of DE, potentially enhancing the toxicities. This study is aimed to assess iron-doped DE-induced cardiopulmonary toxicity in an established in ovo early-in-life inhalation exposure chicken embryo model, and to explore potential mechanisms. Ferrocene (205, 410, 820,1640 mg/L, equivalent to 75, 150, 300, 600 ppm iron mass) was added to diesel fuel, DE was collected from a diesel generator, and then exposed to embryonic day 18-19 chicken embryo via in ovo inhalation. Hatched chickens were kept for 0, 1, or 3 months, and then sacrificed. Histopathology, electrocardiography along with biochemical methods were used to assess cardiopulmonary toxicities. For mechanistic investigation, inhibitor for ferroptosis (ferrostatin-1) or Acyl hydrocarbon receptor (PDM2) were administered before DE (with or without iron-doping), and the cardiopulmonary toxicities were compared. Characterization of DE particles indicated that addition of ferrocene significantly elevated iron content. Additionally, the contents of major toxic polycyclic aromatic hydrocarbons decreased following addition of 820 mg/L ferrocene, but increased at other doses. Remarkable cardiopulmonary toxicities, in the manifestation of elevated heart rates, cardiac remodeling and cardiac/pulmonary fibrosis were observed in animals exposed to iron-doped DEs, in which the addition of ferrocene significantly enhanced the toxicities. Both ferrostatin-1 and PDM2 pretreatment could effectively alleviate the observed effects in animals exposed to iron-doped DE. Inhibition of AhR signaling seems to be capable of alleviating changes to ferroptosis related molecules following exposure to iron-doped DE, while inhibition of ferroptosis does not seem to affect AhR signaling molecules. In summary, iron-doping with ferrocene to diesel enhanced DE-induced cardiopulmonary toxicities in chicken embryos. Ferroptosis and AhR signaling both seem to participate in this process, in which AhR signaling seems to affect ferroptosis.

One-dimensional photonic crystal enhancing spin-to-orbital angular momentum conversion for single-particle tracking.

Single-particle tracking (SPT) is an immensely valuable technique for studying a variety of processes in the life sciences and physics. It can help researchers better understand the positions, paths, and interactions of single objects in systems that are highly dynamic or require imaging over an extended time. Here, we propose an all-dielectric one-dimensional photonic crystal (1D PC) that enhances spin-to-orbital angular momentum conversion for three-dimensional (3D) SPTs. This well-designed 1D PC can work as a substrate for optical microscopy. We introduce this effect into the interferometric scattering (iSCAT) technique, resulting in a double-helix point spread function (DH-PSF). DH-PSF provides more uniform Fisher information for 3D position estimation than the PSFs of conventional microscopy, such as encoding the axial position of a single particle in the angular orientation of DH-PSF lobes, thus providing a means for 3D SPT. This approach can address the challenge of iSCAT in 3D SPT because DH-PSF iSCAT will not experience multiple contrast inversions when a single particle travels along the axial direction. DH-PSF iSCAT microscopy was used to record the 3D trajectory of a single microbead attached to the flagellum, facilitating precise analysis of fluctuations in motor dynamics. Its ability to track single nanoparticles, such as 3D diffusion trajectories of 20 nm gold nanoparticles in glycerol solution, was also demonstrated. The DH-PSF iSCAT technique enabled by a 1D PC holds potential promise for future applications in physical, biological, and chemical science.

Microfluidic sperm trap array for single-cell flagellar analysis with unrestricted 2D flagellar movement.

Sperm capture techniques that immobilize sperm to halt their motility are essential for the long-term analysis of individual sperm. These techniques are beneficial in assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) by allowing selective screening of sperm. However, there is a notable lack of high-throughput and non-destructive sperm capture methods that allow the flagellum to beat freely, which is crucial for accurately reflecting the behavior of unfettered, freely swimming sperm. To bridge this gap, we introduce a novel microfluidic device specifically engineered to capture sperm without restricting flagellar motion. The design utilizes sperm's innate boundary-following behavior in both 3D and 2D environments to direct them into a capture zone. Once captured, the sperm head is restrained while the flagellum remains free to exhibit natural beating patterns. Utilizing this device, we explore the effects of hyperactivating agents, temperature, and their combined influence on the dynamics of bovine sperm flagella. The unrestricted flagellar motion offered by our device yields two prominent advantages: it mirrors the flagellar behavior of free-swimming sperm, ensuring research findings are consistent with natural sperm activity, and it prevents imaging overlap between the flagellum and the capture structures, simplifying the automation of flagellar tracking and analysis. This technological advancement facilitates the collection of waveform parameters along the entire flagellum, addressing inconsistencies that have arisen in previous research due to differing measurement sites, and enabling precise extraction of sperm behavioral properties.

Vertical confinement enhances surface exploration in bacterial twitching motility.

Bacteria are often found in environments where space is limited, and they attach themselves to surfaces. One common form of movement on these surfaces is bacterial twitching motility, which is powered by the extension and retraction of type IV pili. Although twitching motility in unrestricted conditions has been extensively studied, the effects of spatial confinement on this behaviour are not well understood. In this study, we explored the diffusive properties of individual twitching Pseudomonas aeruginosa cells in spatially confined conditions. We achieved this by placing the bacteria between layers of agarose and glass, and then tracking the long-term twitching motility of individual cells. Interestingly, we found that while confinement reduced the immediate speed of twitching, it paradoxically increased diffusion. Through a combination of mechanical and geometrical analysis, as well as numerical simulations, we showed that this increase in diffusion could be attributed to mechanical factors. The constraint imposed by the agarose altered the diffusion pattern of the bacteria from normal to superdiffusion. These findings provide valuable insights into the motile behaviour of bacteria in confined environments.

Developmental 6:2 FTCA exposure impairs renal development in chicken embryos via IGF signaling.

6:2 fluorotelomer carboxylic acid (6:2 FTCA) is a perfluorooctanoic acid (PFOA) substitute, which is supposedly less accumulative and toxic than PFOA. However, 6:2 FTCA is structurally similar to PFOA, and there had already been reports about its toxicities comparable to PFOA. The aim of the current study is to assess potential effects of developmental exposure to 6:2 FTCA on the development of kidney in chicken embryo and to investigate underlying mechanism. Fertile chicken eggs were exposed to 1.25 mg/kg, 2.5 mg/kg or 5 mg/kg doses of 6:2 FTCA, or 2 mg/kg PFOA, then incubated to hatch. Serum and kidney of hatchling chickens were collected. Blood urea nitrogen (BUN) and creatinine (Cre) levels were measured with commercially available kits. Morphology of kidney was assessed with histopathology. To further reveal molecular mechanism of observed endpoints, IGF signaling molecules were assessed in the kidney samples with qRT-PCR, results indicated that IGFBP3 is a potentially crucial molecule. Lentiviruses overexpressing or silencing IGFBP3 were designed and applied to enhance/suppress the expression of IGFBP3 in developing chicken embryo for further verification of its role in the observed effects. Disrupted nephron formation, in the manifestation of decreased glomeruli number/area and increased serum BUN/Cre levels, was observed in the animals developmentally exposed to 6:2 FTCA. Correspondingly, IGF signaling molecules (IGF1, IGF1R and IGFBP3) were affected by 6:2 FTCA exposure. Meanwhile, overexpression of IGFBP3 effectively alleviated such changes, while silencing of IGFBP3 mimicked observed effects. In conclusion, developmental exposure to 6:2 FTCA is associated with disrupted chicken embryo renal development, in which IGFBP3 seems to be a remarkable contributor, suggesting potential health risks for human and other species. Further risk assessments and mechanistic works are necessary.

Potassium-mediated bacterial chemotactic response.

Bacteria in biofilms secrete potassium ions to attract free swimming cells. However, the basis of chemotaxis to potassium remains poorly understood. Here, using a microfluidic device, we found that Escherichia coli can rapidly accumulate in regions of high potassium concentration on the order of millimoles. Using a bead assay, we measured the dynamic response of individual flagellar motors to stepwise changes in potassium concentration, finding that the response resulted from the chemotaxis signaling pathway. To characterize the chemotactic response to potassium, we measured the dose-response curve and adaptation kinetics via an Förster resonance energy transfer (FRET) assay, finding that the chemotaxis pathway exhibited a sensitive response and fast adaptation to potassium. We further found that the two major chemoreceptors Tar and Tsr respond differently to potassium. Tar receptors exhibit a biphasic response, whereas Tsr receptors respond to potassium as an attractant. These different responses were consistent with the responses of the two receptors to intracellular pH changes. The sensitive response and fast adaptation allow bacteria to sense and localize small changes in potassium concentration. The differential responses of Tar and Tsr receptors to potassium suggest that cells at different growth stages respond differently to potassium and may have different requirements for potassium.

Speed-dependent bacterial surface swimming.

Solid surfaces submerged in liquid in natural environments alter bacterial swimming behavior and serve as platforms for bacteria to form biofilms. In the initial stage of biofilm formation, bacteria detect surfaces and increase the intracellular level of the second messenger c-di-GMP, leading to a reduction in swimming speed. The impact of this speed reduction on bacterial surface swimming remains unclear. In this study, we utilized advanced microscopy techniques to examine the effect of swimming speed on bacterial surface swimming behavior. We found that a decrease in swimming speed reduces the cell-surface distance and prolongs the surface trapping time. Both these effects would enhance bacterial surface sensing and increase the likelihood of cells adhering to the surface, thereby promoting biofilm formation. We also examined the surface-escaping behavior of wild-type Escherichia coli and Pseudomonas aeruginosa, noting distinct surface-escaping mechanisms between the two bacterial species. IMPORTANCE: In the early phase of biofilm formation, bacteria identify surfaces and increase the intracellular level of the second messenger c-di-GMP, resulting in a decrease in swimming speed. Here, we utilized advanced microscopy techniques to investigate the impact of swimming speed on bacterial surface swimming, focusing on Escherichia coli and Pseudomonas aeruginosa. We found that an increase in swimming speed led to an increase in the radius of curvature and a decrease in surface detention time. These effects were explained through hydrodynamic modeling as a result of an increase in the cell-surface distance with increasing swimming speed. We also observed distinct surface-escaping mechanisms between the two bacterial species. Our study suggests that a decrease in swimming speed could enhance the likelihood of cells adhering to the surface, promoting biofilm formation. This sheds light on the role of reduced swimming speed in the transition from motile to sedentary bacterial lifestyles.

Persistent metabolic toxicities following developmental exposure to hexafluoropropylene oxide trimer acid (HFPO-TA): Roles of peroxisome proliferator activated receptor gamma.

BACKGROUND: Hexafluoropropylene oxide trimer acid (HFPO-TA), a perfluorooctanoic acid (PFOA) substitute, exhibited strong affinity and capability to activate peroxisome proliferator activated receptor gamma (PPARγ), a lipid metabolism regulator, suggesting potential to induce metabolic toxicities. METHODS: Fertile chicken eggs were exposed to 0, 0.5, 1 or 2 mg/kg (egg weight) HFPO-TA and incubated until hatch. Serum from 0- and 3- month-old chickens were subjected to liquid chromatography ultra-high resolution mass spectrometry for HFPO-TA concentration, while liver, pancreas and adipose tissue samples were collected for histopathological assessments. In ovo PPARγ reporter and silencing system were established with lentivirus microinjection. qRT-PCR and immunohistochemistry were utilized to evaluate the expression levels of PPARγ downstream genes. RESULTS: In 3-month-old animals developmentally exposed to HFPO-TA, adipose tissue hyperplasia, hepatic steatosis, pancreas islet hypertrophy and elevated serum free fatty acid / insulin levels were observed. Results of reporter assay and qRT-PCR indicated HFPO-TA-mediated PPARγ transactivation in chicken embryo. Silencing of PPARγ alleviated HFPO-TA-induced changes, while PPARγ agonist rosiglitazone mimicked HFPO-TA-induced effects. qRT-PCR and immunohistochemistry revealed that FASN and GPD1 were upregulated following developmental exposure to HFPO-TA in 3-month-old animals. CONCLUSIONS: Developmental exposure to HFPO-TA induced persistent metabolic toxicities in chickens, in which PPARγ played a central role.

Hydrogel dressings for diabetic foot ulcer: A systematic review and meta-analysis.

AIM: To investigate the differences in utility between conventional dressings and hydrogel dressings for the treatment of diabetic foot ulcer (DFU). METHODS: The PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases were systematically searched up to 21 January 2023. Fixed/random-effect models were used to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) for the effect size analysis, with heterogeneity determined by I2 statistics. Subgroup analyses of different classes of hydrogel were also conducted. RESULTS: A total of 15 randomized controlled trials with 872 patients were eligible for the present analysis. Compared with conventional dressings, hydrogel dressings significantly improved the healing rate (OR 4.09, 95% CI 2.83 to 5.91), shortened the healing time (MD -11.38, 95% CI -13.11 to -9.66), enhanced granulation formation (MD -3.60, 95% CI -4.21 to -3.00) and epithelial formation (MD -2.82, 95% CI -3.19 to -2.46), and reduced the incidence of bacterial infection (OR 0.10, 95% CI 0.05 to 0.18). CONCLUSION: The meta-analysis showed that hydrogel dressings are more effective in treating DFU compared with conventional dressings.

Bacterial surface swimming states revealed by TIRF microscopy.

Motility near solid surfaces plays a key role in the life cycle of bacteria and is essential for biofilm formation, biofilm dispersal, and virulence. The alignment of the cell body with the surface during surface swimming impacts bacterial surface sensing. Here, we developed a high-throughput method for characterizing the orientation of the cell body relative to the surface using total internal reflection fluorescence (TIRF) microscopy. The angle between the cell body and the surface was determined by maximizing image cross-correlations between the TIRF image of the cell and a reference library. Utilizing this technique, we surprisingly identified six distinct surface swimming states of Pseudomonas aeruginosa according to the body alignment and the flagellar position. Furthermore, we observed that the near-surface swimming speed is greater in the pull state than in the push state, attributed to hydrodynamic effects near the liquid-solid interface. Hydrodynamic force analysis of the swimming states provided rich insights into the mechanics of bacterial surface swimming. Our technique is readily applicable to the study of surface motility across a wide spectrum of bacterial species.

Long-term exposure to air pollution and risk of insulin resistance: A systematic review and meta-analysis.

OBJECTIVE: The effects of air pollution on metabolism have become a popular research topic, and a large number of studies had confirmed that air pollution exposure could induce insulin resistance (IR) to varying degrees, but the results were inconsistent, especially for the long-term exposures. The aim of the current study was to further investigate the potential effects of air pollution on IR. METHODS: A systematic review and meta-analysis of four electronic databases, including PubMed, Embase, Web of Science and Cochrane were conducted, searching for relevant studies published before June 10, 2023, in order to explore the potential relationships between long-term exposure to air pollution and IR. A total of 10 studies were included for data analysis, including seven cohort studies and three cross-sectional studies. Four major components of air pollution, including PM2.5 (particulate matter with an aerodynamic diameter of 2.5 µm or less), PM10 (particulate matter with an aerodynamic diameter of 10 µm or less), NO2, and SO2 were selected, and each analyzed for the potential impacts on insulin resistance, in the form of adjusted percentage changes in the homeostasis assessment model of insulin resistance (HOMA-IR). RESULTS: This systematic review and meta-analysis showed that for every 1 µg/m³ increase in the concentration of selected air pollutants, PM2.5 induced a 0.40% change in HOMA-IR (95%CI: -0.03, 0.84; I2 =67.4%, p = 0.009), while PM10 induced a 1.61% change (95%CI: 0.243, 2.968; I2 =49.1%, p = 0.001). Meanwhile, the change in HOMA-IR due to increased NO2 or SO2 exposure concentration was only 0.09% (95%CI: -0.01, 0.19; I2 =83.2%, p = 0.002) or 0.01% (95%CI: -0.04, 0.06; I2 =0.0%, p = 0.638), respectively. CONCLUSIONS: Long-term exposures to PM2.5, PM10, NO2 or SO2 are indeed associated with the odds of IR. Among the analyzed pollutants, inhalable particulate matters appear to exert greater impacts on IR.

Flagellar motors of swimming bacteria contain an incomplete set of stator units to ensure robust motility.

Flagellated bacteria, like Escherichia coli, swim by rotating helical flagellar filaments powered by rotary flagellar motors at their base. Motor dynamics are sensitive to the load it drives. It was previously thought that motor load was high when driving filament rotation in free liquid environments. However, torque measurements from swimming bacteria revealed substantially lower values compared to single-motor studies. We addressed this inconsistency through motor resurrection experiments, abruptly attaching a 1-micrometer-diameter bead to the filament to ensure high load. Unexpectedly, we found that the motor works with only half the complement of stator units when driving filament rotation. This suggests that the motor is not under high load during bacterial swimming, which we confirmed by measuring the torque-speed relationship by varying media viscosity. Therefore, the motor operates in an intermediate-load region, adaptively regulating its stator number on the basis of external load conditions. This ensures the robustness of bacterial motility when swimming in diverse load conditions and varying flagella numbers.

Tethered particle motion of the adaptation enzyme CheR in bacterial chemotaxis.

Bacteria perform chemotactic adaptation by sequential modification of multiple modifiable sites on chemoreceptors through stochastic action of tethered adaptation enzymes (CheR and CheB). To study the molecular kinetics of this process, we measured the response to different concentrations of MeAsp for the Tar-only Escherichia coli strain. We found a strong dependence of the methylation rate on the methylation level and established a new mechanism of adaptation kinetics due to tethered particle motion of the methylation enzyme CheR. Experiments with various lengths of the C-terminal flexible chain in the Tar receptor further validated this mechanism. The tethered particle motion resulted in a CheR concentration gradient that ensures encounter-rate matching of the sequential modifiable sites. An analytical model of multisite catalytic reaction showed that this enables robustness of methylation to fluctuations in receptor activity or cell-to-cell variations in the expression of adaptation enzymes and reduces the variation in methylation level among individual receptors.

Endometrial telomerase activity in women with either endometrial cancer or hyperplasia: A systematic review and meta-analysis.

AIM: We performed a systematic review and meta-analysis to assess whether endometrial telomerase activity is associated with endometrial cancer or hyperplasia. METHODS: PubMed, Web of Science, Embase, Scielo, LILAC, and CNKI databases were searched to obtain relevant literature for articles published through June 2022, following PRISMA guidelines and a registered PROSPERO protocol. We included observational studies reporting endometrial telomerase activity in patients with either endometrial cancer or hyperplasia compared with benign endometrial tissue (control women). The Newcastle-Ottawa Scale was used to evaluate the quality of studies. Data were expressed as the odds ratios (OR) and 95 % confidence intervals (CI). Random effects and inverse variance methods were used to meta-analyze associations. The I2 test was used to assess heterogeneity. RESULTS: There were significant associations between endometrial telomerase activity and either endometrial cancer (20 studies, OR = 10.65, 95 % CI 6.39, 17.75, p = 0.00001, I2 = 21 %) or endometrial hyperplasia (nine studies, OR = 3.62, 95 % CI 1.61, 8.13, p = 0.002, I2 = 36 %) compared to women without endometrial cancer and hyperplasia. There was not a significant difference in telomerase activity in women with endometrial cancer compared to those with endometrial hyperplasia (seven studies, OR = 1.03; 95 % CI 0.31, 3.37, p = 0.96, I2 = 49 %). In subgroup analyses, there were no significant differences in telomerase activity in patients with endometrial cancer by type of observational studies and by countries of the studies. CONCLUSION: Endometrial telomerase activity is higher in women with either endometrial cancer or endometrial hyperplasia compared to control women without those lesions.

Flagellar brake protein YcgR interacts with motor proteins MotA and FliG to regulate the flagellar rotation speed and direction.

In E. coli and related species, flagellar brake protein YcgR responds to the elevated intracellular c-di-GMP, decreases the flagellar rotation speed, causes a CCW rotation bias, and regulates bacterial swimming. Boehm et al. suggested that c-di-GMP-activated YcgR directly interacted with the motor protein MotA to curb flagellar motor output. Paul et al. proposed that YcgR disrupted the organization of the FliG C-terminal domain to bias the flagellar rotation. The target proteins are controversial, and the role of motor proteins remains unclear in flagellar rotation speed and direction regulation by YcgR. Here we assayed the motor proteins' affinity via a modified FRET biosensor and accessed the role of those key residue via bead assays. We found that YcgR could interact with both MotA and FliG, and the affinities could be enhanced upon c-di-GMP binding. Furthermore, residue D54 of YcgR-N was needed for FliG binding. The mutation of the FliG binding residue D54 or the MotA binding ones, F117 and E232, restored flagellar rotation speed in wild-type cells and cells lacking chemotaxis response regulator CheY that switched the flagellar rotation direction and decreased the CCW ratio in wild-type cells. We propose that c-di-GMP-activated YcgR regulated the flagellar rotation speed and direction via its interaction with motor proteins MotA and FliG. Our work suggest the role of YcgR-motor proteins interaction in bacterial swimming regulation.

Timescale separation in the coordinated switching of bacterial flagellar motors.

The output of the bacterial chemotaxis signaling pathway, the level of the intracellular regulator CheY-P, modulates the rotation direction of the flagellar motor, thereby regulating bacterial run-and-tumble behavior. The multiple flagellar motors on anE. colicell are controlled by a common cytoplasmic pool of CheY-P. Fluctuation of the CheY-P level was thought to be able to coordinate the switching of multiple motors. Here, we measured the correlation of rotation directions between two motors on a cell, finding that it surprisingly exhibits two well separated timescales. We found that the slow timescale (∼6 s) can be explained by the slow fluctuation of the CheY-P level due to stochastic activity of the chemotactic adaptation enzymes, whereas the fast timescale (∼0.3 s) can be explained by the random pulse-like fluctuation of the CheY-P level, due probably to the activity of the chemoreceptor clusters. We extracted information on the properties of the fast CheY-P pulses based on the correlation measurements. The two well-separated timescales in the fluctuation of CheY-P level help to coordinate multiple motors on a cell and to enhance bacterial chemotactic performance.

Differential Bending Stiffness of the Bacterial Flagellar Hook under Counterclockwise and Clockwise Rotations.

The bacterial hook, as a universal joint coupling rotation of the flagellar motor and the filament, is an important component of the flagellum that propels the bacteria to swim. The mechanical properties of the hook are essential for the flagellum to achieve normal functions. In multiflagellated bacteria such as Escherichia coli, the hook must be compliant so that it can bend for the filaments to form a coherently rotating bundle to generate the thrust when the motor rotates counterclockwise (CCW), yet it also must be rigid so that the bundle can disrupt for the bacteria to tumble to change swimming direction when the motor rotates clockwise (CW). Here, by combining an elastic rod model with high-resolution bead assay to accurately measure the bending stiffness of the hook under CCW or CW rotation in vivo, we elucidate how the hook accomplishes this dual functionality: the hook stiffens under CW rotation, with bending stiffness under CW rotation twice as large as that under CCW rotation. This enables a robust run-and-tumble swimming motility for multiflagellated bacteria.

Precise Measurement of the Stoichiometry of the Adaptive Bacterial Flagellar Switch.

The cytoplasmic ring (C-ring) of the bacterial flagellar motor controls the motor rotation direction, thereby controlling bacterial run-and-tumble behavior. The C-ring has been shown to undergo adaptive remodeling in response to changes in motor directional bias. However, the stoichiometry and arrangement of the C-ring is still unclear due to contradiction between the results from fluorescence studies and cryo-electron microscopy (cryo-EM) structural analysis. Here, by using the copy number of FliG molecules (34) in the C-ring as a reference, we precisely measured the copy numbers of FliM molecules in motors rotating exclusively counterclockwise (CCW) and clockwise (CW). We surprisingly found that there are on average 45 and 58 FliM molecules in CW and CCW rotating motors, respectively, which are much higher than previous estimates. Our results suggested a new mechanism of C-ring adaptation, that is, extra FliM molecules could be bound to the primary C-ring with probability depending on the motor rotational direction. We further confirmed that all of the FliM molecules in the C-ring function in chemotaxis signaling transduction because all of them could be bound by the chemotactic response regulator CheY-P. Our measurements provided new insights into the structure and arrangement of the flagellar switch. IMPORTANCE The bacterial flagellar switch can undergo adaptive remodeling in response to changes in motor rotation direction, thereby shifting its operating point to match the output of the chemotaxis signaling pathway. However, it remains unclear how the flagellar switch accomplishes this adaptive remodeling. Here, via precise fluorescence studies, we measured the absolute copy numbers of the critical component in the switch for motors rotating counterclockwise and clockwise, obtaining much larger numbers than previous relative estimates. Our results suggested a new mechanism of adaptive remodeling of the flagellar switch and provided new insights for updating the conformation spread model of the switch.

Hexafluoropropylene oxide tetramer acid (HFPO-TeA)-induced developmental toxicities in chicken embryo: Peroxisome proliferator-activated receptor Alpha (PPARα) is involved.

Hexafluoropropylene oxide tetramer acid (HFPO-TeA) is an emerging environmental contaminant, with environmental presence but limited toxicological information. To investigate its potential developmental toxicities, various doses of HFPO-TeA exposure were achieved in chicken embryos via air cell injection, and the exposed embryos were incubated until hatch. Within 24 h of hatch, the hatchling chickens were assessed with electrocardiography and histopathology for toxicological evaluation. For mechanistic investigation, in ovo silencing of PPARα was achieved via lentivirus microinjection, then the morphological/functional endpoints along with protein expression levels of PPARα-regulated genes were assessed. HFPO-TeA exposure in chicken embryo resulted in developmental cardiotoxicity and hepatotoxicity. Specifically, decreased right ventricular wall thickness, increased heart rate and hepatic steatosis were observed, whereas silencing of PPARα resulted in alleviation of observed toxicities. Western blotting for EHHADH and FABPs suggested that developmental exposure to HFPO-TeA effectively increased the expression levels of both targets in hatchling chicken heart and liver tissue samples, while PPARα silencing prevented such changes, suggesting that PPARα and its downstream genes are playing critical roles in HFPO-TeA induced developmental toxicities.

Effects of L-carnitine supplementation on glucolipid metabolism: a systematic review and meta-analysis.

Background: L-carnitine supplementation has been utilized against glucolipid metabolism disruption. However, to the best of our knowledge, no meta-analysis process has analyzed the effects of L-carnitine supplementation on insulin resistance, fasting blood glucose, lipid metabolism, and liver enzyme levels in adults. Methods: Through the analysis and screening of 12 221 studies, 15 studies were selected from eligible trials for meta-analysis. Meta-analysis was performed in a random effect model with heterogeneity determined by I2, and subgroup analyses were used to further identify the source of heterogeneity. Result: The results showed significant effects of L-carnitine on FBG (MD = -4.94 mg dL-1, 95% CI: -7.07 to -2.82), insulin (MD = -0.99 µU mL-1, 95% CI: -1.41 to -0.56), HOMA-IR (MD = -0.58, 95% CI: -0.77 to -0.38), TG (MD = -11.22 mg dL-1, 95% CI: -19.21 to -3.22), TC (MD = -6.45 mg dL-1, 95% CI: -9.95 to -2.95, LDLc (MD = -8.28 mg dL-1, 95% CI: -11.08 to -5.47), and ALT (MD = -19.71 IU L-1, 95% CI: -36.45 to -2.96). However, no significant effect of L-carnitine supplementation was observed in HDLc (MD = -0.77 mg dL-1, 95% CI: -0.10 to -1.63) or AST (MD = -11.05 IU L-1, 95% CI: -23.08 to 0.99). The duration of carnitine supplementation was negatively associated with mean differences in FBG, as assessed by meta-regression. Conclusion: The current meta-analysis revealed that L-carnitine may have favorable effects on glucolipid profile, especially insulin, FBG, HOMA-IR, TG, TC, LDLc, and ALT levels.