Percent duration of heart rate acceleration within the respiratory cycle: a novel approach to assess heart rate asymmetry.

Accelerations and decelerations of heart rate are nonsymmetrical in the magnitude and number of beat-to-beat changes. The asymmetric features of heart rate variability are related to respiratory durations. To explore the link between respiration and heart rate asymmetry (HRA), we evaluated 14 seated, healthy young adults who breathed with nine combinations of inspiration duration (TI) and expiration duration (TE), chosen respectively from 2, 4, and 6 s. A 5-min R-R interval (RRI) time series was obtained from each study period to construct an averaged pattern waveform relative to the respiratory cycle. We observed that the time interval between inspiration onset and RRI minimum progressively lengthened as TI and TE increased. The time interval between expiration onset and RRI maximum also lengthened when TE increased but shortened when TI increased. Consequently, TI and TE had different effects on the acceleration time (AT; from RRI maximum to RRI minimum) and deceleration time (DT; from RRI minimum to RRI maximum). The percentage of AT within the respiratory cycle showed a strong correlation with traditional Guzik's (r = 0.862, P < 0.001) and Porta's (r = 0.878, P < 0.001) indexes of HRA assessed in a Poincaré plot analysis. These findings suggest that, in addition to considering the magnitude and number of beat-to-beat changes, HRA can also be assessed based on another aspect: the duration of consecutive changes. The stepwise link between the duration of heart rate change and respiratory duration provides insight into the mechanisms connecting respiration to HRA.NEW & NOTEWORTHY In healthy adults who regulated their breathing across nine combinations of inspiration and expiration durations, we used averaged pattern waveform technique to quantify the durations of heart rate acceleration and deceleration within the respiratory cycle. The percent duration of acceleration showed a strong correlation with traditional heart rate asymmetry indexes, which evaluate the magnitude and number of beat-to-beat changes. This new approach opens a window to explore the asymmetric features of heart rate variability.

Different effects of inspiratory duration and expiratory duration on heart rate deceleration capacity and heart rate asymmetry.

PURPOSE: Low values of heart rate deceleration capacity (DC) and heart rate asymmetry (HRA) are associated with cardiovascular risks. Slow respiration has been proven to enhance the magnitudes of these indexes, but individual inspiratory (TI) and expiratory (TE) durations were not controlled in most studies. This study aims to examine whether the effects of TI and TE on these indexes would be the same and, if not, how to adjust TI and TE to maximize the effect of slow respiration. METHODS: We evaluated 14 seated healthy young adults who randomly controlled their breathing to nine combinations of TI and TE, each chosen respectively from 2, 4, and 6 s. A 5-min R-R interval time series was obtained from each study period for further analysis. RESULTS: The magnitude of DC increased when TI or TE increased, while that of acceleration capacity (AC) remained almost unchanged by TI. We further defined a new index as 100 × DC2/(DC2 + AC2) and found it to be correlated with conventional Guzik's (r = 0.94) and Porta's (r = 0.99) indexes of HRA during different combinations of TI and TE. Increasing TI and increasing TE both enhanced the magnitudes of HRA indexes, with TI taking effect when ≤ 4 s, and TE taking effect when > 4 s. DC and HRA indexes were maximized with a TI of 4 s and a TE of 6 s. CONCLUSION: We suggest that a TI of 3-4 s with a TE of 7-6 s is an appropriate standard for slow respiration.

Comparative analysis of visual-thermal perceptions and emotional responses in outdoor open spaces: Impacts of look-up vs. look-forward viewing perspectives.

Horizontal and vertical viewing perspectives exert varying influences on the environmental perceptions and emotional states of college students. Despite this, scant research addresses the impact on this demographic. We selected typical campus open spaces for comprehensive physical parameter assessments, encompassing meteorological and spatial characteristics. A cohort of 36 healthy college students participated in a questionnaire survey designed to ascertain shifts in visual comfort, thermal comfort, and emotional responses when viewing landscapes in look-forward and look-up orientations. Key findings following both viewing modalities included: 1) a notable rise in mean visual comfort vote (MVCV), by 1.22 for look-forward and 1.01 for look-up, with a pronouncedly higher sunlight sensation vote (SSV) for the latter orientation; 2) a significant increase in thermal comfort vote (TCV), although the difference in increments between the two viewing angles was minimal; 3) Positive affect (PA) exhibited considerable improvement in both viewing conditions, while negative affect (NA) was markedly reduced in the look-up condition relative to look-forward viewing; 4) The SSV was predominantly influenced by the trunk ratio and canopy-to-trunk ratio, with substantial weights of 31.47% and 32.15%, respectively. Landscape element diversity emerged as the most critical factor affecting visual comfort vote (VCV) and aesthetic assessment score (AAS), with overwhelming weights of 70.67% and 63.15%, respectively. Moreover, the leaf ratio was identified as the chief determinant of emotional responses. Our results provide insights into the design of campus spaces for enhanced student well-being.

Synthesis and utilization of polyol-modified high specific surface area Ca(OH)2: an investigation.

Calcium hydroxide (Ca(OH)2) finds widespread use in the petrochemical industry, particularly in flue gas desulfurization applications. However, its conventional usage is limited by its inherently low specific surface area, hampering its efficiency. To address this limitation, this study aims to develop a simple and industrially scalable preparation process for Ca(OH)2 with a high specific surface area, thereby enhancing its effectiveness in various applications. This study aimed to develop a preparation process for making Ca(OH)2 with a high specific surface area, suitable for industry and easy to make. Ca(OH)2 with a specific surface area of 41.555 m2/g was successfully synthesized by incorporating polyols during lime digestion. The prepared high specific surface area Ca(OH)2 is more than five times the specific surface area of ordinary Ca(OH)2. Incorporation of polyols within the lime digestion process induces a reduction in both Ca(OH)2 grain size and particle dimensions, concurrently amplifying the specific surface area and optimizing mass transfer efficiency. Specifically, the desulfurization breakthrough time for Ca(OH)2 subject to a 15% triethanolamine modification was notably extended to 879 s, surpassing the desulfurization breakthrough time of unaltered Ca(OH)2 by more than tenfold. Moreover, the modified Ca(OH)2 exhibited remarkable efficacy in neutralizing acidic wastewater. A new approach for the preparation of high-performance Ca(OH)2 is proposed in this study, which could facilitate the industrial production of Ca(OH)2 with high specific surface area.

Mechanism of Circ_HECW2 regulating osteoblast apoptosis in osteoporosis by attenuating the maturation of miR-1224-5p.

BACKGROUND: Osteoporosis (OP) poses a significant clinical challenge with escalating morbidity. This study explores Circ_HECW2 expression in OP patients and its regulatory role in lipopolysaccharide (LPS)-induced osteoblast apoptosis. METHODS: Circ_HECW2 expression in OP patient serum and healthy controls was quantified using RT-qPCR. Diagnostic value of Circ_HECW2 for OP was assessed via ROC curve. Pearson's correlation model examined associations between indicators. Human osteoblasts HFOB1.19, treated with LPS, were analyzed for Circ_HECW2, pre-miR-1224, miR-1224-5p, and PDK2 mRNA levels. TUNEL assay determined cell apoptosis and Western blot assessed cleaved-caspase-3 protein levels. RNase R resistance assay and actinomycin D assay confirmed Circ_HECW2's cyclic structure. RNA pull-down and dual-luciferase reporter assay verified binding relationships between Circ_HECW2 and miR-1224 and between miR-1224-5p and PDK2. RESULTS: Circ_HECW2 exhibited elevated expression in OP patients with diagnostic significance and a negative correlation with lumbar T-score. LPS co-culture increased Circ_HECW2 expression in HFOB1.19 cells, significantly elevating apoptosis index and cleaved-caspase-3. Circ_HECW2 downregulation inhibited HFOB1.19 apoptosis, reduced pre-miR-1224 expression, and elevated mature miR-1224-5p. Circ_HECW2 bound to pre-miR-1224, and inhibiting miR-1224-5p reversed the effect of Circ_HECW2 downregulation on osteoblast apoptosis. miR-1224-5p targeted PDK2 transcription. CONCLUSION: Circ_HECW2, highly expressed in OP, holds diagnostic significance and reflects disease severity. Circ_HECW2 reduces mature miR-1224-5p by binding to pre-miR-1224, upregulating PDK2, and facilitating LPS-induced osteoblast apoptosis.

Kellerin alleviates cerebral ischemic injury by inhibiting ferroptosis via targeting Akt-mediated transcriptional activation of Nrf2.

BACKGROUND: Ischemic stroke (IS) is characterized as a detrimental cerebrovascular disease with high mortality and disability. Ferroptosis is a novel mechanism involved in neuronal death. There is a close connection between IS and ferroptosis, and inhibiting ferroptosis may provide an effective strategy for treating IS. Our previous investigations have discovered that kellerin, the active compound of Ferula sinkiangensis K. M. Shen, possesses the capability to shield against cerebral ischemia injury. PURPOSE: Our objective is to clarify the relationship between the neuroprotective properties of kellerin against IS and its ability to modulate ferroptosis, and investigate the underlying regulatory pathway. STUDY DESIGN: We investigated the impact and mechanism of kellerin in C57BL/6 mice underwent middle cerebral artery occlusion/reperfusion (MCAO/R) as well as SH-SY5Y cells exposed to oxygen-glucose deprivation/ re-oxygenation (OGD/R). METHODS: The roles of kellerin on neurological severity, cerebral infarction and edema were investigated in vivo. The regulatory impacts of kellerin on ferroptosis, mitochondrial damage and Akt/Nrf2 pathway were explored. Molecular docking combined with drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) were performed to analyze the potential target proteins for kellerin. RESULTS: Kellerin protected against IS and inhibited ferroptosis in vivo. Meanwhile, kellerin improved the neuronal damage caused by OGD/R and suppressed ferroptosis by inhibiting the production of mitochondrial ROS in vitro. Further we found that kellerin directly interacted with Akt and enhanced its phosphorylation, leading to the increase of Nrf2 nuclear translocation and its downstream antioxidant genes expression. Moreover, kellerin's inhibitory effect on ferroptosis and mitochondrial ROS release was eliminated by inhibiting Akt/Nrf2 pathway. CONCLUSIONS: Our study firstly demonstrates that the neuroprotective properties of kellerin against IS are related to suppressing ferroptosis through inhibiting the production of mitochondrial ROS, in which its modulation on Akt-mediated transcriptional activation of Nrf2 plays an important role. This finding shed light on the potential mechanism that kellerin exerts therapeutic effects in IS.

A quinolinyl resveratrol derivative alleviates acute ischemic stroke injury by promoting mitophagy for neuroprotection via targeting CK2α'.

Ischemic stroke (IS) is a serious threat to human health. The naturally derived small molecule (E)-5-(2-(quinolin-4-yl) ethenyl) benzene-1,3-diol (RV01) is a quinolinyl analog of resveratrol with great potential in the treatment of IS. The aim of this study was to investigate the potential mechanisms and targets for the protective effect of the RV01 on IS. The mouse middle cerebral artery occlusion and reperfusion (MCAO/R) and oxygen-glucose deprivation and reperfusion (OGD/R) models were employed to evaluate the effects of RV01 on ischemic injury and neuroprotection. RV01 was found to significantly increase the survival of SH-SY5Y cells and prevent OGD/R-induced apoptosis in SH-SY5Y cells. Furthermore, RV01 reduced oxidative stress and mitochondrial damage by promoting mitophagy in OGD/R-exposed SH-SY5Y cells. Knockdown of CK2α' abolished the RV01-mediated promotion on mitophagy and alleviation on mitochondrial damage as well as neuronal injury after OGD/R. These results were further confirmed by molecular docking, drug affinity responsive target stability and cellular thermal shift assay analysis. Importantly, in vivo study showed that treatment with the CK2α' inhibitor CX-4945 abolished the RV01-mediated alleviation of cerebral infarct volume, brain edema, cerebral blood flow and neurological deficit in MCAO/R mice. These data suggest that RV01 effectively reduces damage caused by acute ischemic stroke by promoting mitophagy through its interaction with CK2α'. These findings offer valuable insights into the underlying mechanisms through which RV01 exerts its therapeutic effects on IS.

miR-9 utilizes precursor pathways in adaptation to alcohol in mouse striatal neurons.

microRNA-9 (miR-9) is one of the most abundant microRNAs in the mammalian brain, essential for its development and normal function. In neurons, it regulates the expression of several key molecules, ranging from ion channels to enzymes, to transcription factors broadly affecting the expression of many genes. The neuronal effects of alcohol, one of the most abused drugs in the world, seem to be at least partially dependent on regulating the expression of miR-9. We previously observed that molecular mechanisms of the development of alcohol tolerance are miR-9 dependent. Since a critical feature of alcohol action is temporal exposure to the drug, we decided to better understand the time dependence of alcohol regulation of miR-9 biogenesis and expression. We measured the effect of intoxicating concentration of alcohol (20 mM ethanol) on the expression of all major elements of miR-9 biogenesis: three pri-precursors (pri-mir-9-1, pri-mir-9-2, pri-mir-9-3), three pre-precursors (pre-mir-9-1, pre-mir-9-2, pre-mir-9-3), and two mature microRNAs: miR-9-5p and miR-9-3p, using digital PCR and RT-qPCR, and murine primary medium spiny neurons (MSN) cultures. We subjected the neurons to alcohol based on an exposure/withdrawal matrix of different exposure times (from 15 min to 24 h) followed by different withdrawal times (from 0 h to 24 h). We observed that a short exposure increased mature miR-9-5p expression, which was followed by a gradual decrease and subsequent increase of the expression, returning to pre-exposure levels within 24 h. Temporal changes of miR-9-3p expression were complementing miR-9-5p changes. Interestingly, an extended, continuous presence of the drug caused a similar pattern. These results suggest the presence of the adaptive mechanisms of miR-9 expression in the presence and absence of alcohol. Measurement of miR-9 pre- and pri-precursors showed further that the primary effect of alcohol on miR-9 is through the mir-9-2 precursor pathway with a smaller contribution of mir-9-1 and mir-9-3 precursors. Our results provide new insight into the adaptive mechanisms of neurons to alcohol exposure. It would be of interest to determine next which microRNA-based mechanisms are involved in a transition from the acute, intoxicating effects of alcohol to the chronic, addictive effects of the drug.