Dynamics of CH/n hydrogen bond networks probed by time-resolved CARS spectroscopy.

Hydrogen bond (HB) networks are essential for stabilizing molecular structures in solution and govern the solubility and functionality of molecules in an aqueous environment. HBs are important in biological processes such as enzyme-substrate interactions, protein folding, and DNA replication. However, the exact role of weakly polarized C-H bonds as HB proton donors in solution, such as CH/n HBs, remains mostly unknown. Here, we employ a novel approach focusing on vibrational dephasing to investigate the coherence relaxation of induced dipoles in C-H bonds within CH/n HB networks, utilizing time-resolved coherent anti-Stokes Raman scattering (T-CARS) spectroscopy. Using a representative binary system of dimethyl sulfoxide (DMSO)-water, known for its C-H backboned HB system (i.e., C-H⋯S), we observed an increase in the dephasing time of the C-H bending mode with increasing water content until a percolation threshold at a 6 : 1 water : DMSO molar ratio, where the trend is reversed. These results provide compelling evidence for the existence of C-H⋯S structures and underscore the presence of a percolation effect, suggesting a critical threshold where long-range connectivity is disputed.

Low- and moderate-intensity aerobic exercise improves the physiological acclimatization of lowlanders on the Tibetan plateau.

This study investigates whether exercise as a strategy for improving physical fitness at sea level also offers comparable benefits in the unique context of high altitudes (HA), considering the physiological challenges of hypoxic conditions. Overall, 121 lowlanders who had lived on the Tibetan Plateau for >2 years and were still living at HA during the measurements were randomly classified into four groups. Each individual of the low-intensity (LI), moderate-intensity (MI), and high-intensity (HI) groups performed 20 sessions of aerobic exercise at HA (3680 m) over 4 weeks, while the control group (CG) did not undergo any intervention. Physiological responses before and after the intervention were observed. The LI and MI groups experienced significant improvement in cardiopulmonary fitness (0.27 and 0.35 L/min increases in peak oxygen uptake [ V ˙ $\dot{\mathrm{V}}$ O2peak], both p < 0.05) after exercise intervention, while the hematocrit (HCT) remained unchanged (p > 0.05). However, HI exercise was less efficient for cardiopulmonary fitness of lowlanders (0.02 L/min decrease in V ˙ $\dot{\mathrm{V}}$ O2peak, p > 0.05), whereas both the HCT (1.74 %, p < 0.001) and glomerular filtration rate (18.41 mL/min, p < 0.001) increased with HI intervention. Therefore, LI and MI aerobic exercise, rather than HI, can help lowlanders in Tibet become more acclimated to the HA by increasing cardiopulmonary function and counteracting erythrocytosis.

Subregions of the fusiform gyrus are differentially involved in the attentional mechanism supporting visual mental imagery in depression.

BACKGROUND: Impaired visual mental imagery is an important symptom of depression and has gradually become an intervention target for cognitive behavioral therapy. METHODS: Our study involved a total of 25 healthy controls (HC) and 23 individuals with moderate depressive symptoms (MD). This study explored the attentional mechanism supporting visual mental imagery impairments in depression using the Vividness of Visual Imagery Questionnaire (VVIQ), attentional network test (ANT), and resting-state functional magnetic resonance imaging (rs-fMRI). The intrinsic activity of attention-related regions relative to those supporting visual mental imagery was identified in depression patients. In addition, a meta-analysis was used to describe the cognitive function related to this intrinsic activity. RESULTS: The global correlation (GCOR) of the right anterior fusiform gyrus (FG) was decreased in depression patients. Attention-related areas were concentrated in the right posterior FG; the anterior and posterior functional connectivity (FC) of the FG was decreased in depression patients. Graph theoretic analysis showed that the degree of the right anterior FG was decreased, the degree of the anterior insula was increased, and the negative connection between these two regions was strengthened in depression patients. In addition, the degree of the right anterior FG, the FC between the subregions of the right FG, and the FC between the right anterior FG and insula were correlated with VVIQ scores; however, this correlation was not significant in depression patients. The meta-analysis suggested that the changes in the anterior FG in depressed patients may stem from difficulties of semantic memory retrieval. CONCLUSION: The changed intrinsic activity of subregions of the FG relative to the semantic memory retrieval may be associated with visual mental imagery impairments in depression.

The effects of long-term high-altitude exposure on cognition: A meta-analysis.

Long-term high altitudes (HA) exposure's impact on cognition has yielded inconsistent findings in previous research. To address this, we conducted a meta-analysis of 49 studies (6191 individuals) to comprehensively evaluate this effect. Moderating factors such as cognitive task type, altitude (1500-2500 m, 2500-4000 m, and above 4000 m), residential type (chronic and lifelong), adaptation level and demographic factors were analyzed. Cognitive tasks were classified into eight categories: perceptual processes, psychomotor function, long-term memory, working memory, inhibitory control, problem-solving, language, and others. Results revealed a moderate negative effect of HA on cognitive performance (g = -.40, SE =.18, 95% CI = -.76 to -.05). Psychomotor function and long-term memory notably experience the most pronounced decline, while working memory and language skills show moderate decreases due to HA exposure. However, perceptual processes, inhibitory control, and problem-solving abilities remain unaffected. Moreover, residing at altitudes above 4000 m and being a HA immigrant are associated with significant cognitive impairment. In summary, our findings indicate a selective adaptation of cognitive performance to HA conditions.

Perceived stress and brain connectivity in subthreshold depression: Insights from eyes-closed and eyes-open states.

Perceived stress is an acknowledged risk factor for subthreshold depression (StD), and fluctuations in perceived stress are thought to disrupt the harmony of brain networks essential for emotional and cognitive functioning. This study aimed to elucidate the relationship between eye-open (EO) and eye-closed (EC) states, perceived stress, and StD. We recruited 27 individuals with StD and 33 healthy controls, collecting resting state fMRI data under both EC and EO conditions. We combined intrinsic connectivity and seed-based functional connectivity analyses to construct the functional network and explore differences between EC and EO conditions. Graph theory analysis revealed weakened connectivity strength in the right superior frontal gyrus (SFG) and right median cingulate and paracingulate gyrus (MCC) among participants with StD, suggesting an important role for these regions in the stress-related emotions dysregulation. Notably, altered SFG connectivity was observed to significantly relate to perceived stress levels in StD, and the SFG connection emerges as a neural mediator potentially influencing the relationship between perceived stress and StD. These findings highlight the role of SFG and MCC in perceived stress and suggest that understanding EC and EO states in relation to these regions is important in the neurobiological framework of StD. This may offer valuable perspectives for early prevention and intervention strategies in mental health disorders.

The neuroimmune pathway of high-altitude adaptation: influence of erythrocytes on attention networks through inflammation and the autonomic nervous system.

Introduction: Many studies have shown that the functional adaptation of immigrants to high-altitude is closely related to oxygen transport, inflammatory response and autonomic nervous system. However, it remains unclear how human attention changes in response to hypoxia-induced neurophysiological activity during high-altitude exposure. Methods: In the present study, we analyzed the relationship between hypoxic-induced neurophysiological responses and attention networks in 116 immigrants (3,680 m) using an attention network test to simultaneously record electroencephalogram and electrocardiogram in combination with specific routine blood markers. Results: Our analysis revealed that red blood cells exert an indirect influence on the three attention networks, mediated through inflammatory processes and heart rate variability. Discussion: The present study provides experimental evidence for the role of a neuroimmune pathway in determining human attention performance at high- altitude. Our findings have implications for understanding the complex interactions between physiological and neurocognitive processes in immigrants adapting to hypoxic environments.

Dose-effect of exercise intervention on heart rate variability of acclimatized young male lowlanders at 3,680 m.

This study investigated whether exercise could improve the reduced HRV in an environment of high altitude. A total of 97 young, healthy male lowlanders living at 3,680 m for >1 year were recruited. They were randomized into four groups, of which three performed-low-, moderate-, and high-intensity (LI, MI, HI) aerobic exercise for 4 weeks, respectively. The remaining was the control group (CG) receiving no intervention. For HI, compared to other groups, heart rate (p = 0.002) was significantly decreased, while standard deviation of RR intervals (p < 0.001), SD2 of Poincaré plot (p = 0.046) and the number of successive RR interval pairs that differ by > 50 ms divided by total number of RR (p = 0.032), were significantly increased after intervention. For MI, significantly increase of trigonometric interpolation in NN interval (p = 0.016) was observed after exercise. Further, a decrease in systolic blood pressure (SBP) after high-intensity exercise was found significantly associated with an increase in SD2 (r = - 0.428, p = 0.042). These results indicated that there was a dose effect of different intensities of aerobic exercise on the HRV of acclimatized lowlanders. Moderate and high-intensity aerobic exercise would change the status of the autonomic nervous system (ANS) and decrease the blood pressure of acclimatized lowlanders exposed to high altitude.

The relationship between attention networks and individual differences in visual mental imagery vividness - An EEG study.

Previous research has established a strong link between attention and visual mental imagery, but it's remained uncertain whether attention networks influence individual differences in the vividness of visual mental imagery. In our study, we examined 140 participants, assessing the vividness of imagery using the Vividness of Visual Imagery Questionnaire in both eyes-open and eyes-closed conditions. We employed the Attention Network Test, coupled with EEG recording, to characterize three attention sub-networks: alerting, orienting, and executive control. To pinpoint the specific attentional networks associated with the vividness of visual mental imagery, we utilized latent profile analysis to categorize participants into distinct subgroups. Additionally, we constructed a regression mixture model to explore how attention networks predict different latent categories of visual imagery vividness. Our findings revealed that the efficiency of the alerting network, as indicated by the N1 component, demonstrated a positive correlation with the vividness of visual imagery. This electrophysiological evidence underscores the role of the alerting network in shaping individual differences in the vividness of visual mental imagery.

Rapid azoospermia classification by stimulated Raman scattering and second harmonic generation microscopy.

Disease diagnosis and classification pose significant challenges due to the limited capabilities of traditional methods to obtain molecular information with spatial distribution. Optical imaging techniques, utilizing (auto)fluorescence and nonlinear optical signals, introduce new dimensions for biomarkers exploration that can improve diagnosis and classification. Nevertheless, these signals often cover only a limited number of species, impeding a comprehensive assessment of the tissue microenvironment, which is crucial for effective disease diagnosis and therapy. To address this challenge, we developed a multimodal platform, termed stimulated Raman scattering and second harmonic generation microscopy (SRASH), capable of simultaneously providing both chemical bonds and structural information of tissues. Applying SRASH imaging to azoospermia patient samples, we successfully identified lipids, protein, and collagen contrasts, unveiling molecular and structural signatures for non-obstructive azoospermia. This achievement is facilitated by LiteBlendNet-Dx (LBNet-Dx), our diagnostic algorithm, which achieved an outstanding 100% sample-level accuracy in classifying azoospermia, surpassing conventional imaging modalities. As a label-free technique, SRASH imaging eliminates the requirement for sample pre-treatment, demonstrating great potential for clinical translation and enabling molecular imaging-based diagnosis and therapy.

A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform.

To accurately phenocopy human biology in vitro, researchers have been reducing their dependence on standard, static two-dimensional (2D) cultures and instead are moving towards three-dimensional (3D) and/or multicellular culture techniques. While these culture innovations are becoming more commonplace, there is a growing body of research that illustrates the benefits and even necessity of recapitulating the dynamic flow of nutrients, gas, waste exchange and tissue interactions that occur in vivo. However, cost and engineering complexity are two main factors that hinder the adoption of these technologies and incorporation into standard laboratory workflows. We developed LATTICE, a plug-and-play microfluidic platform able to house up to eight large tissue or organ models that can be cultured individually or in an interconnected fashion. The functionality of the platform to model both healthy and diseased tissue states was demonstrated using 3D cultures of reproductive tissues including murine ovarian tissues and human fallopian tube explants (hFTE). When exogenously exposed to pathological doses of gonadotropins and androgens to mimic the endocrinology of polycystic ovarian syndrome (PCOS), subsequent ovarian follicle development, hormone production and ovulation copied key features of this endocrinopathy. Further, hFTE cilia beating decreased significantly only when experiencing continuous media exchanges. We were then able to endogenously recreate this phenotype on the platform by dynamically co-culturing the PCOS ovary and hFTE. LATTICE was designed to be customizable with flexibility in 3D culture formats and can serve as a powerful automated tool to enable the study of tissue and cellular dynamics in health and disease in all fields of research.

What is cooking in your kitchen: seeing "invisible" with time-resolved coherent anti-Stokes Raman spectroscopy.

Cooking oil is a critical component of human food and its main component, lipid, is influential to health, but assessing its authenticity and quality can be challenging due to its complex chemical composition. In this study, we introduce a novel application of time-resolved coherent anti-Stokes Raman scattering (T-CARS) spectroscopy for detecting adulteration and understanding the mechanisms of lipid oxidation in various cooking oils. Our research surpasses the limitations of conventional spontaneous Raman spectroscopy, demonstrating that intra-molecular interactions from unsaturated bonds in triglycerides significantly influence vibrational dephasing time. We observed that these dephasing times, although diverse initially, converge to a similar value after heating cycles. Notably, a longer vibrational dephasing of the CH2 symmetric stretching mode was found to correlate with a higher lipid oxidation rate. These findings underscore the potential of T-CARS in identifying and characterizing subtle molecular interactions, offering a transformative approach to understanding molecular dynamics. This research paves the way for broader applications of T-CARS across fields such as chemistry, biomedicine, and material science, marking a significant advancement in the development of innovative analytical techniques.

Spatial multiplexing for robust optical vortex transmission with optical nonlinearity.

Optical vortex beams, with phase singularity characterized by a topological charge (TC), introduces a new dimension for optical communication, quantum information, and optical light manipulation. However, the evaluation of TCs after beam propagation remains a substantial challenge, impeding practical applications. Here, we introduce vortices in lateral arrays (VOILA), a novel spatial multiplexing approach that enables simultaneous transmission of a lateral array of multiple vortices. Leveraging advanced learning techniques, VOILA effectively decodes TCs, even in the presence of strong optical nonlinearities simulated experimentally. Notably, our approach achieves substantial improvements in single-shot bandwidth, surpassing single-vortex scheme by several orders of magnitude. Furthermore, our system exhibits precise fractional TC recognition in both linear and nonlinear regimes, providing possibilities for high-bandwidth communication. The capabilities of VOILA promise transformative contributions to optical information processing and structured light research, with significant potential for advancements in diverse fields.

Long-term high-altitude exposure influences task-related representations in visual working memory.

Objective: Human working memory is impaired when individuals are exposed to high altitudes, however, whether the capacity of visual working memory is affected remains unclear. This study combined a lateralized change detection task and event-related potentials analysis to explore changes in visual working memory capacity among individuals who emigrated from a low-altitude environment to Tibet (a high-altitude environment). Materials and methods: Thirty-five college students were recruited from Tibet University as the high-altitude (HA) group, and thirty-six low-altitude (LA) students were enrolled from South China Normal University (sea level) as the LA group. We measured participants' contralateral delay activity (CDA) under different memory loads. Results: ERP component analysis showed that both the HA and LA groups reached an asymptote at memory load four. However, the contralateral and ipsilateral activity of the HA and LA groups shows different patterns. The results showed a significantly larger contralateral activity for the LA group than for the HA group at memory load one (p = 0.04, Cohen's d = 0.52) and load three (p = 0.02, Cohen's d = 0.61). Additionally, we found marginally larger contralateral activity at memory load four for the LA group (p = 0.06, Cohen's d = 0.47), but not at memory load two (p = 0.10) or load five (p = 0.12). No significant differences were observed for ipsilateral activity. In addition, we observed that the HA group performed larger ipsilateral activity than contralateral activity under each memory load, compared with the LA group. Conclusion: These findings demonstrated that the attentional resource of long-term HA exposure is more captured by task-irrelevant information, potentially due to impaired inhibitory control, which makes it difficult for them to exclude the interference of task-irrelevant information.

Effects of Cyanobacterial Harmful Algal Bloom Toxin Microcystin-LR on Gonadotropin-Dependent Ovarian Follicle Maturation and Ovulation in Mice.

BACKGROUND: Cyanobacterial harmful algal blooms (CyanoHABs) originate from the excessive growth or bloom of cyanobacteria often referred to as blue-green algae. They have been on the rise globally in both marine and freshwaters in recently years with increasing frequency and severity owing to the rising temperature associated with climate change and increasing anthropogenic eutrophication from agricultural runoff and urbanization. Humans are at a great risk of exposure to toxins released from CyanoHABs through drinking water, food, and recreational activities, making CyanoHAB toxins a new class of contaminants of emerging concern. OBJECTIVES: We investigated the toxic effects and mechanisms of microcystin-LR (MC-LR), the most prevalent CyanoHAB toxin, on the ovary and associated reproductive functions. METHODS: Mouse models with either chronic daily oral or acute intraperitoneal exposure, an engineered three-dimensional ovarian follicle culture system, and human primary ovarian granulosa cells were tested with MC-LR of various dose levels. Single-follicle RNA sequencing, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, immunohistochemistry (IHC), and benchmark dose modeling were used to examine the effects of MC-LR on follicle maturation, hormone secretion, ovulation, and luteinization. RESULTS: Mice exposed long term to low-dose MC-LR did not exhibit any differences in the kinetics of folliculogenesis, but they had significantly fewer corpora lutea compared with control mice. Superovulation models further showed that mice exposed to MC-LR during the follicle maturation window had significantly fewer ovulated oocytes. IHC results revealed ovarian distribution of MC-LR, and mice exposed to MC-LR had significantly lower expression of key follicle maturation mediators. Mechanistically, in both murine and human granulosa cells exposed to MC-LR, there was reduced protein phosphatase 1 (PP1) activity, disrupted PP1-mediated PI3K/AKT/FOXO1 signaling, and less expression of follicle maturation-related genes. DISCUSSION: Using both in vivo and in vitro murine and human model systems, we provide data suggesting that environmentally relevant exposure to the CyanoHAB toxin MC-LR interfered with gonadotropin-dependent follicle maturation and ovulation. We conclude that MC-LR may pose a nonnegligible risk to women's reproductive health by heightening the probability of irregular menstrual cycles and infertility related to ovulatory disorders. https://doi.org/10.1289/EHP12034.

Association between the acceleration of access to visual awareness of grating orientation with higher heart rate at high-altitude.

Many studies have indicated a strong relationship between cardiac and brain activities, both of which are sensitive to high-altitude exposure. This study combined a consciousness access task and electrocardiograms (ECG) to uncover conscious awareness in response to high-altitude exposure and its relation to cardiac activity. When compared with the low-altitude groups, the behavioral results showed that the high-altitude participants shortened the time of access to visual awareness of grating orientation, which was accompanied by a faster heart rate, excluding the influence of pre-stimulus heart rate, extent of cardiac deceleration after presenting the stimulus, and task difficulty. Although there were post-stimulation cardiac deceleration and post-response acceleration at both high and low altitudes, a slight increase in heart rate after stimulation at high altitudes may indicate that participants at high altitudes could quickly readjust their attention to the target stimulus. More importantly, the drift diffusion model (DDM) was used to fit the access time distribution of all participants. These results suggest that shorter time at high altitudes might be due to the lower threshold, suggesting that less evidence in high-altitude participants was required to access visual consciousness. The participants' heart rates also negatively predicted the threshold through a hierarchical drift diffusion modeling (HDDM) regression. These findings imply that individuals with higher heart rates at high altitudes have a greater cognitive burden.

Neurodynamics of Awareness Detection in Tibetan Immigrants: Evidence from Electroencephalography Analysis.

The psychological effects of long-term exposure to high-altitude environments have attracted great attention. These effects are usually attributed to the diminished cognitive resources due to high-altitude exposure. This study employed electroencephalography (EEG) to investigate the effects of exposure duration on awareness detection tasks. Neither reaction time nor accuracy showed the direct effects of the exposure duration, so did the model indexes obtained from drift diffusion model analysis. However, event-related potentials (ERP) analysis revealed that exposure duration was associated with changes in the visual awareness negativity (VAN) and the late positivity (LP) components, which in turn affected reaction time. Specifically, longer exposure durations were associated with lower VAN and higher LP, resulting in shorter reaction times and greater drift rate. In contrast to previous studies, the reverse relationship between VAN and LP may reflect a compensatory response to the reduced cognitive resources caused by high-altitude exposure. Additionally, increased LP and shorter reaction times with exposure duration may reflect a resistance to the high-altitude environment. We also conducted time-frequency analysis and found that theta power did not vary with exposure duration, suggesting that the reduction in cognitive resources remains stable in these individuals over time. Overall, our study provides new insights into the dynamic effects of high-altitude environments on awareness detection in the presence of reduced cognitive resources.

Spatial sterol metabolism unveiled by stimulated Raman imaging.

Spatiotemporal dynamics of small-molecule metabolites have gained increasing attention for their essential roles in deciphering the fundamental machinery of life. However, subcellular-level regulatory mechanisms remain less studied, particularly due to a lack of tools to track small-molecule metabolites. To address this challenge, we developed high-resolution stimulated Raman scattering (SRS) imaging of a genetically engineered model (GEM) to map metabolites in subcellular resolution. As a result, an unexpected regulatory mechanism of a critical metabolite, sterol, was discovered in yeast by amplifying the strength of vibrational imaging by genetic modulation. Specifically, isozymes of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) were evident to promote ergosterol distribution to distinct subcellular locations, where ergosterol was enriched by a local HMGR-directed synthesis. The heterogeneity of this expression pattern thus provides new insights into sterol metabolism and related disease treatment strategies. These findings demonstrate SRS-GEM as a promising platform for new possibilities in investigating metabolic regulation, disease mechanisms, and biopharmaceutical research.

Gabor and Non-Gabor Neural Representations Are Shared between Visual Perception and Mental Imagery.

Visual perception and mental imagery have been shown to share a hierarchical topological visual structure of neural representation, despite the existence of dissociation of neural substrate between them in function and structure. However, we have limited knowledge about how the visual hierarchical cortex is involved in visual perception and visual imagery in a unique and shared fashion. In this study, a data set including a visual perception and an imagery experiment with human participants was used to train 2 types of voxel-wise encoding models. These models were based on Gabor features and voxel activity patterns of high-level visual cortex (i.e., fusiform face area, parahippocampal place area, and lateral occipital complex) to predict activity in the early visual cortex (EVC, i.e., V1, V2, V3) during perception, and then tested with respect to the generalization of these models to mental imagery. Our results showed that during perception and imagery, activities in the EVC could be independently predicted by the Gabor features and activity of high-level visual cortex via voxel-wise encoding models, which suggested that perception and imagery might share neural representation in the EVC. We further found Gabor-specific and non-Gabor-specific patterns of neural response to stimuli in the EVC, which were shared by perception and imagery. These findings provide insight into the mechanisms of how visual perception and imagery share representation in the EVC.

Depression and suicide attempts in Chinese adolescents with mood disorders: the mediating role of rumination.

Mood disorders (MD) are often associated with a higher incidence of suicidal behavior, especially in adolescent patients. However, the mechanisms by which depression affects suicide attempts in adolescents with MD remain poorly elucidated. Therefore, the purpose of this study was to determine the incidence, risk factors, and clinical correlates of suicide attempts in Chinese adolescent patients with MD, as well as the inter-relationship between depressive symptoms, rumination, and suicide attempts, and the role of rumination in mediating depression and suicide attempts. A total of 331 MD adolescent patients aged 11 ~ 18 years were recruited from a psychiatric hospital. Suicide attempts were assessed with the MINI Suicide Scale. Depressed symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). To assess rumination, we used the 21-item Chinese version of the Ruminative Responses Scale (RRS). Overall, the percentage of suicide attempts among MD adolescents was 51.96%, with a higher percentage of females (58.62%) than males (36.36%). Compared to non-suicide attempters, suicide attempters had higher scores on PHQ-9, RRS, depression-related, brooding, and reflective pondering. Gender and RRS were independently associated with suicide attempts. Rumination played a fully mediating role between depression and suicide attempts. In addition, the mediating effect of depression between rumination and suicide attempts was not significant. The incidence of suicide attempts was higher in MD adolescents than in general adolescents. Gender and rumination were associated with suicide attempts in MD adolescents. Moreover, rumination mediated the correlation between depressive symptoms and suicide attempts, suggesting that rumination may be an important intervention component for clinical staff to prevent suicidal behavior in adolescents with MD.