Experimental evidence to understand mechanical causes of retinal detachment following blunt trauma.

PURPOSE: This study aimed to perform an in vitro experiment to simulate retinal detachment caused by blunt impact, and provide experimental evidence to understand mechanical causes of traumatic retinal detachment. METHODS: The experiment was conducted on twenty-two fresh porcine eyes using a bespoke pendulum testing device at two energy levels (0.1J for low energy and 1.0J for high energy). We examined dynamic forces and mechanical responses to the impact, including global deformations, intraocular pressure changes and the energy absorption. Another set of twenty-two eyes underwent pathological examination immediately after being subjected to blunt impact. Twelve additional intact eyes were examined as controls. All pathological sections were scored to indicate whether retinal detachment had occurred. RESULTS: A dynamic variation in intraocular pressure was detected following impact and exhibited an approximate sinusoidal oscillation-attenuation profile. The peaks of impact force were 12.9 ± 1.9 N at low-energy level and 34.8 ± 9.8 N at high-energy level, showing a significant difference (p < 0.001). The positive and negative peaks of intraocular pressure were 149.4 ± 18.9 kPa and -10.9 ± 7.2 kPa at low-energy level, and 274.5 ± 55.2 kPa and -35.7 ± 23.7 kPa at high-energy level, showing significant differences (p < 0.001 for both levels). Retinal detachments were observed in damaged eyes while few detachments were found in control eyes. The occurrence rate of retinal detachment differed significantly (p < 0.05) between the high- and low-energy impact groups. CONCLUSIONS: This study provided experimental evidence that shockwaves produced by blunt trauma break the force equilibrium and lead to the oscillation and negative pressure, which mainly contribute to traumatic retinal detachment.

Extreme atmospheric rivers in a warming climate.

Extreme atmospheric rivers (EARs) are responsible for most of the severe precipitation and disastrous flooding along the coastal regions in midlatitudes. However, the current non-eddy-resolving climate models severely underestimate (~50%) EARs, casting significant uncertainties on their future projections. Here, using an unprecedented set of eddy-resolving high-resolution simulations from the Community Earth System Model simulations, we show that the models' ability of simulating EARs is significantly improved (despite a slight overestimate of ~10%) and the EARs are projected to increase almost linearly with temperature warming. Under the Representative Concentration Pathway 8.5 warming scenario, there will be a global doubling or more of the occurrence, integrated water vapor transport and precipitation associated with EARs, and a more concentrated tripling for the landfalling EARs, by the end of the 21st century. We further demonstrate that the coupling relationship between EARs and storms will be reduced in a warming climate, potentially influencing the predictability of future EARs.

Interhemispheric multisensory perception and Bayesian causal inference.

In daily life, our brain needs to eliminate irrelevant signals and integrate relevant signals to facilitate natural interactions with the surrounding. Previous study focused on paradigms without effect of dominant laterality and found that human observers process multisensory signals consistent with Bayesian causal inference (BCI). However, most human activities are of bilateral interaction involved in processing of interhemispheric sensory signals. It remains unclear whether the BCI framework also fits to such activities. Here, we presented a bilateral hand-matching task to understand the causal structure of interhemispheric sensory signals. In this task, participants were asked to match ipsilateral visual or proprioceptive cues with the contralateral hand. Our results suggest that interhemispheric causal inference is most derived from the BCI framework. The interhemispheric perceptual bias may vary strategy models to estimate the contralateral multisensory signals. The findings help to understand how the brain processes the uncertainty information coming from interhemispheric sensory signals.

Age-related differences in upper limb motor performance and intrinsic motivation during a virtual reality task.

BACKGROUND: In recent years, virtual reality (VR) has evolved from an alternative to a necessity in older adults for health, medical care, and social interaction. Upper limb (UL) motor skill, is an important ability in manipulating VR systems and represents the brain's regulation of movements using the UL muscles. In this study, we used a haptic-feedback Virtual Box and Block Test (VBBT) system and an Intrinsic Motivation Inventory (IMI) to examine age-related differences in UL motor performance and intrinsic motivation in VR use. The findings will be helpful for the development of VR applications for older adults. METHODS: In total, 48 young and 47 older volunteers participated in our study. The parameters including VBBT score, number of velocity peaks, velocity, grasping force and trajectory length were calculated to represent the task performance, manual dexterity, coordination, perceptive ability and cognitive ability in this study. RESULTS: Age-related differences could be found in all the parameters (all p <  0.05) in VR use. Regression analysis revealed that the task performance of young adults was predicted by the velocity and trajectory length (R2 = 64.0%), while that of older adults was predicted by the number of velocity peaks (R2 = 65.6%). Additionally, the scores of understandability, relaxation and tiredness were significantly different between the two groups (all p <  0.05). In older adults, the understandability score showed large correlation with the IMI score (|r| = 0.576, p <  0.001). In young adults, the correlation was medium (|r| = 0.342, p = 0.017). No significant correlation was found between the IMI score and VBBT score (|r| = 0.142, p = 0.342) in older adults, while a medium correlation (|r| = 0.342, p = 0.017) was found in young adults. CONCLUSIONS: The findings demonstrated that decreased smoothness in motor skills dominated the poor VR manipulation in older adults. The experience of understandability is important for older adults' intrinsic motivation in VR use.

Eye movement characteristics in a mental rotation task presented in virtual reality.

Introduction: Eye-tracking technology provides a reliable and cost-effective approach to characterize mental representation according to specific patterns. Mental rotation tasks, referring to the mental representation and transformation of visual information, have been widely used to examine visuospatial ability. In these tasks, participants visually perceive three-dimensional (3D) objects and mentally rotate them until they identify whether the paired objects are identical or mirrored. In most studies, 3D objects are presented using two-dimensional (2D) images on a computer screen. Currently, visual neuroscience tends to investigate visual behavior responding to naturalistic stimuli rather than image stimuli. Virtual reality (VR) is an emerging technology used to provide naturalistic stimuli, allowing the investigation of behavioral features in an immersive environment similar to the real world. However, mental rotation tasks using 3D objects in immersive VR have been rarely reported. Methods: Here, we designed a VR mental rotation task using 3D stimuli presented in a head-mounted display (HMD). An eye tracker incorporated into the HMD was used to examine eye movement characteristics during the task synchronically. The stimuli were virtual paired objects oriented at specific angular disparities (0, 60, 120, and 180°). We recruited thirty-three participants who were required to determine whether the paired 3D objects were identical or mirrored. Results: Behavioral results demonstrated that the response times when comparing mirrored objects were longer than identical objects. Eye-movement results showed that the percent fixation time, the number of within-object fixations, and the number of saccades for the mirrored objects were significantly lower than that for the identical objects, providing further explanations for the behavioral results. Discussion: In the present work, we examined behavioral and eye movement characteristics during a VR mental rotation task using 3D stimuli. Significant differences were observed in response times and eye movement metrics between identical and mirrored objects. The eye movement data provided further explanation for the behavioral results in the VR mental rotation task.

Adipocyte Thyroid Hormone ß Receptor-Mediated Hormone Action Fine-tunes Intracellular Glucose and Lipid Metabolism and Systemic Homeostasis.

Thyroid hormone (TH) has a profound effect on energy metabolism and systemic homeostasis. Adipose tissues are crucial for maintaining whole-body homeostasis; however, whether TH regulates systemic metabolic homeostasis through its action on adipose tissues is unclear. Here, we demonstrate that systemic administration of triiodothyronine (T3), the active form of TH, affects both inguinal white adipose tissue (iWAT) and whole-body metabolism. Taking advantage of the mouse model lacking adipocyte TH receptor (TR) α or TRß, we show that TRß is the major TR isoform that mediates T3 action on the expression of genes involved in multiple metabolic pathways in iWAT, including glucose uptake and use, de novo fatty acid synthesis, and both UCP1-dependent and -independent thermogenesis. Moreover, our results indicate that glucose-responsive lipogenic transcription factor in iWAT is regulated by T3, thereby being critically involved in T3-regulated glucose and lipid metabolism and energy dissipation. Mice with adipocyte TRß deficiency are susceptible to diet-induced obesity and metabolic dysregulation, suggesting that TRß in adipocytes may be a potential target for metabolic diseases. ARTICLE HIGHLIGHTS: How thyroid hormone (TH) achieves its diverse biological activities in the regulation of metabolism is not fully understood. Whether TH regulates systemic metabolic homeostasis via its action on white adipose tissue is unclear. Adipocyte TH receptor (TR) ß mediates the triiodothyronine effect on multiple metabolic pathways by targeting glucose-responsive lipogenic transcription factor in white adipose tissue; mice lacking adipocyte TRß are susceptible to high-fat diet-induced metabolic abnormalities. TRß in white adipocytes controls intracellular and systemic metabolism and may be a potential target for metabolic diseases.

Aberrant elevation of FTO levels promotes liver steatosis by decreasing the m6A methylation and increasing the stability of SREBF1 and ChREBP mRNAs.

Previous studies have indicated an association of fat mass and obesity-associated (FTO) with nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. This study aimed to decipher the complex role of FTO in hepatic lipid metabolism. We found that a decrease in N6-methyladenosine (m6A) RNA methylation in the liver of mice fed with a high-fat diet (HFD) was accompanied by an increase in FTO expression. Overexpression of FTO in the liver promoted triglyceride accumulation by upregulating the expression of lipogenic genes. Mechanistical studies revealed that FTO could stabilize the mRNAs of sterol regulatory element binding transcription factor 1 (SREBF1) and carbohydrate responsive element binding protein (ChREBP), two master lipogenic transcription factors, by demethylating m6A sites. Knockdown of either SREBF1 or ChREBP attenuated the lipogenic effect of FTO, suggesting that they are bona fide effectors for FTO in regulating lipogenesis. Insulin could stimulate FTO transcription through a mechanism involving the action of intranuclear insulin receptor beta, while knockdown of FTO abrogated the lipogenic effect of insulin. Inhibition of FTO by entacapone decreased the expression of SREBF1, ChREBP, and downstream lipogenic genes, ameliorating liver steatosis in HFD-fed mice. Thus, our study established a critical role of FTO in both the insulin-regulated hepatic lipogenesis and the pathogenesis of NAFLD and provided a potential strategy for treating NAFLD.

Triiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation.

The thyroid hormone (TH)-controlled recruitment process of brown adipose tissue (BAT) is not fully understood. Here, we show that long-term treatment of T3, the active form of TH, increases the recruitment of thermogenic capacity in interscapular BAT of male mice through hyperplasia by promoting the TH receptor α-mediated adipocyte progenitor cell proliferation. Our single-cell analysis reveals the heterogeneous nature and hierarchical trajectory within adipocyte progenitor cells of interscapular BAT. Further analyses suggest that T3 facilitates cell state transition from a more stem-like state towards a more committed adipogenic state and promotes cell cycle progression towards a mitotic state in adipocyte progenitor cells, through mechanisms involving the action of Myc on glycolysis. Our findings elucidate the mechanisms underlying the TH action in adipocyte progenitors residing in BAT and provide a framework for better understanding of the TH effects on hyperplastic growth and adaptive thermogenesis in BAT depot at a single-cell level.

The role of low-frequency oscillations in three-dimensional perception with depth cues in virtual reality.

Currently, vision-related neuroscience studies are undergoing a trend from simplified image stimuli toward more naturalistic stimuli. Virtual reality (VR), as an emerging technology for visual immersion, provides more depth cues for three-dimensional (3D) presentation than two-dimensional (2D) image. It is still unclear whether the depth cues used to create 3D visual perception modulate specific cortical activation. Here, we constructed two visual stimuli presented by stereoscopic vision in VR and graphical projection with 2D image, respectively, and used electroencephalography to examine neural oscillations and their functional connectivity during 3D perception. We find that neural oscillations are specific to delta and theta bands in stereoscopic vision and the functional connectivity in the two bands increase in cortical areas related to visual pathways. These findings indicate that low-frequency oscillations play an important role in 3D perception with depth cues.

A simple indentation technique for identifying localized liquefaction of the vitreous body.

Identification of vitreous liquefaction (VL) is important for investigating some eye pathologies related to changes in the mechanical properties of the vitreous, such as posterior vitreous detachment or retinal detachment. However, because of the extremely high-water content, characterization of the structural and mechanical properties of the vitreous remains a challenge. In the current study, a simple indentation test was performed on the fresh vitreous, partially liquefied vitreous and water, using a mechanical testing machine with a high-precision load cell. Pressure loads on the indenter changing with time for different samples were obtained to characterize their mechanical properties. VL identification was achieved based on a comparison of relative differences in some typical mechanical parameters (e.g. the pressure at the moment of the insertion (P0), the pressure at the steady mechanical state (P∞) and the time when the pressure on the indenter declined to one half the initial value (t1/2)) between 1) partially liquefied vitreous and fresh vitreous samples and 2) partially liquefied vitreous and water samples. The results indicated that P0 of the partially liquefied vitreous was almost half that of fresh vitreous (p < 0.05) and approximately 1.5 times that of water (p < 0.05). t1/2 of the partially liquefied vitreous was approximately 1.4 times higher than that of fresh vitreous (p < 0.05) and approximately 80% of that of water (p < 0.05). It is concluded that P0 and t1/2 can be used as indicators to identify localized liquefaction of the vitreous.

Chaetocin: A review of its anticancer potentials and mechanisms.

Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines. Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo. Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression, inducing cancer cell apoptosis (intrinsic and extrinsic), enhancing autophagy, inducing cell cycle arrest, and inhibiting tumour angiogenesis, invasion, and migration. The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper, and the prospective applications of chaetocin in cancer prevention and therapy are also discussed. This review aimed to summarize the recent advances in the antitumor activity of chaetocin and to provide a rationale for further exploring the potential application of chaetocin in overcoming cancer in the future.

miR-183 and miR-96 orchestrate both glucose and fat utilization in skeletal muscle.

Our knowledge of the coordination of fuel usage in skeletal muscle is incomplete. Whether and how microRNAs are involved in the substrate selection for oxidation is largely unknown. Here we show that mice lacking miR-183 and miR-96 have enhanced muscle oxidative phenotype and altered glucose/lipid homeostasis. Moreover, loss of miR-183 and miR-96 results in a shift in substrate utilization toward fat relative to carbohydrates in mice. Mechanistically, loss of miR-183 and miR-96 suppresses glucose utilization in skeletal muscle by increasing PDHA1 phosphorylation via targeting FoxO1 and PDK4. On the other hand, loss of miR-183 and miR-96 promotes fat usage in skeletal muscle by enhancing intramuscular lipolysis via targeting FoxO1 and ATGL. Thus, our study establishes miR-183 and miR-96 as master coordinators of fuel selection and metabolic homeostasis owing to their capability of modulating both glucose utilization and fat catabolism. Lastly, we show that loss of miR-183 and miR-96 can alleviate obesity and improve glucose metabolism in high-fat diet-induced mice, suggesting that miR-183 and miR-96 may serve as therapeutic targets for metabolic diseases.

Hepatic miR-378 modulates serum cholesterol levels by regulating hepatic bile acid synthesis.

Rationale: An improved understanding of thyroid hormone (TH) action on cholesterol metabolism will facilitate the identification of novel therapeutic targets for hypercholesterolemia. TH-regulated microRNAs (miRNAs) have been implicated in TH-controlled biological processes; however, whether and how TH-regulated miRNAs mediate the cholesterol-lowering effect of TH remains unclear. Our aim was to identify TH-regulated microRNAs that have cholesterol-lowering effects and explore the underlying mechanism. Method: Microarray and RNA-seq were performed to identify TH-regulated microRNAs and the genes regulated by mmu-miR-378-3p (miR-378) in the liver of mice, respectively. Recombinant adenoviruses encoding miR-378, Mafg, and shRNA for Mafg, antagomiR-378, liver-specific miR-378 transgenic mice, and miR-378 knockout mice were employed to investigate the roles of hepatic miR-378 and MAFG in cholesterol and bile acid homeostasis. The levels of bile salt species were determined by using UFLC-Triple-time of flight/MS. Results: Here, we show that hepatic miR-378 is positively regulated by TH. Transient overexpression of miR-378 in the liver of mice reduces serum cholesterol levels, accompanied with an increase in the expression of key enzymes in primary bile acid synthetic pathways and corresponding increases in biliary and fecal bile acid levels. Consistently, liver-specific miR-378 transgenic mice with moderate overexpression of hepatic miR-378 display decreased serum cholesterol levels and resistance to diet-induced hypercholesterolemia, while mice lacking miR-378 exhibit defects in bile acid and cholesterol homeostasis. Mechanistically, hepatic miR-378 regulates the expression of key enzymes in both classic and alternative bile acid synthetic pathways through MAFG, a transcriptional repressor, thereby modulating bile acid and cholesterol metabolism. Conclusions: TH-responsive hepatic miR-378 is capable of modulating serum cholesterol levels by regulating both the classic and alternative BA synthetic pathways. Our study not only identifies a previously undescribed role of hepatic miR-378 but also provides new cholesterol-lowering approaches.

Association of CYP2C19 Polymorphism with Clopidogrel Resistance in Patients with Acute Coronary Syndrome in China.

BACKGROUND The relationship between clopidogrel-resistance (CR) and polymorphism located in genes encoding clopidogrel metabolism-related enzymes has not been fully explored. Thus far, few studies on CR-associated polymorphism have been conducted in the Chinese population. The purpose of this study was to identify CYP2C19 polymorphism associated with CR in patients with acute coronary syndrome in China. MATERIAL AND METHODS There were 125 patients with acute coronary syndromes (ACS) selected for this study. Of these, 27 patients (21.6%) showed CR (less than 10% reduction in platelet accumulation rate), while the remaining 98 patients (78.4%) were non-clopidogrel-resistant (NCR). RESULTS There were significant differences in the allele frequencies of CYP2C19 (rs4244285) (P=0.03) and CYP2C19 (rs4986893) (P=0.005) between the 2 groups; however, there was no significant difference in allele frequencies of ABCB1 (rs1045642) (P=0.661) and PON1 (rs662) (P=0.690) between the 2 groups. The null allele in the CYP2C19 (rs4244285) [odds ratio (OR)=5.317, 95% confidence interval (CI) 1.542-26.428, P=0.001] and CYP2C19 (rs4986893) (OR=4.295, 95%CI 1.312-17.517, P=0.013) is one of the causes of CR in patients with ACS in China. CONCLUSIONS The CYP2C19 polymorphism (rs4244285 and rs4986893) is the correlative factor of CR in patients with ACS in China. It was found that the null allele in the CYP2C19 polymorphism was related to the higher CR risk. According to the key role of CYP2C19 in the clopidogrel activation and the evaluated role of CYP2C19 in this study, further studies should be carried out to formulate therapeutic alternative methods for CR in patients with ACS.

Protective Effects of Baicalin on Experimental Myocardial Infarction in Rats.

OBJECTIVE: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. METHODS: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. RESULTS: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). CONCLUSION: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.

Protective effects of baicalin on experimental myocardial infarction in rats

Abstract Objective: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. Methods: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. Results: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). Conclusion: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.

Differences in body composition and physical functions associated with sarcopenia in Chinese elderly: reference values and prevalence.

This study investigates the age-related differences in skeletal muscle mass (SM), muscle strength and physical performance in mainland Chinese. Based on available data, the reference values (criteria) for the definition of sarcopenia in elderly Chinese were explored. Body composition measurements were obtained using a bioelectrical impedance analyzer (BIA); muscle strength was determined by handgrip strength (HS); and physical function was evaluated by the subjects' 6-m gait speed (GS). In this study, HS and GS declined significantly after 55 years and very dramatically after 75 years. Appendicular SM index of <7.61kg/m(2) (males) and <6.43kg/m(2) (females); HS of <27kg (males) and <16kg (females); and GS of <0.98m/s (males) and <0.88m/s (females) were considered as low SM, low HS and low GS. Applying these suggested criteria to the study population, there were 9.55% and 6.63% of the subjects with low SM, 20.10% and 18.46% with low GS, and 14.07% and 15.38% with low HS in elderly males and females, respectively. Utilizing Asian Working Group for Sarcopenia (AWGS) criteria in our population results in a very low prevalence of low SM and low GS. If Western criteria for sarcopenia were adopted, the prevalence of low GS and low HS would be 2-4 times higher in the studied population, also exhibiting significant gender differences. These findings indicate that it is necessary to establish an outcomes-based and ethnic-specific set of reference values for the diagnosis of sarcopenia in elderly Chinese.

[Study on the optical properties of semiconductor nanocrystalline powder using photoacoustic technology].

The optical properties of semiconductor nanocrystalline powder were studied by using photoacoustic spectroscopy technique. The band gap and the optical absorption coefficient of semiconductor nanocrystalline powder of TiO2, ZnO and Al-doped ZnO were measured by normalized photoacoustic spectroscopy technique. The results show that the optical properties of semiconductor nanocrystalline powder relate to particle size and particle shape. The band gap and the optical absorption coefficient of semiconductor nanocrystalline powder can be controlled by its fabricating techniques. By doping and changing the size and the shape of nanocrystals, changing the optical and electrical properties was achieved.