Ginkgolic Acid (GA) Inhibits the Growth of OCa by Inhibiting lncRNA MALAT1/JAK2 Axis

Objective. We aimed to observe the impact of ginkgolic acid (GA) on the proliferation and metastasis ability of ovarian cancer (OCa) cells and to further explore whether GA affects the malignant progress of OCa via regulating the lncRNA MALAT1/JAK2 axis. Methods. OCa cells SKOV3 and CAOV3 were administered with 1 ng/ml GA, 5 ng/ml GA, 10 ng/ml GA, 20 ng/ml GA, and DSMO as control, respectively. The cell proliferation and migration ability of the abovementioned cells in each group were measured by CCK-8 test and Transwell experiments. The expression levels of lncRNA MALAT1 and JAK2 protein were examined by qRT-PCR and western blot, respectively. Subsequently, in OCa cells treated with GA, lncRNA MALAT1 overexpression vector was transfected to continue to detect the proliferation activity and migration ability of each treatment group. Finally, the regulation of GA on activity of lncRNA MALAT1/JAK2 axis in OCa cells was further explored in nude mice. Results. Our data showed that the proliferation inhibition rate of cells at each ginkgolic acid concentration was higher than that of the control group ( P < 0.05 ), suggesting that GA has an inhibitory influence on the proliferation of OCa cells, in a dose-dependent way. GA was able to inhibit the proliferation rate and migration ability of OCa cells. Administration of ginkgolic acid downregulated the levels of lncRNA MALAT1 and JAK2 protein. Overexpression of lncRNA MALAT1 partially reversed the inhibited OCa proliferative capacity caused by GA treatment. Consistent with the results observed in vitro, we also found that the OCa tumor weight and volume of nude mice injected with lncRNA MALAT1 overexpression vector were enhanced and JAK2 protein level increased remarkably in comparison to the ginkgolic acid group. Conclusions. In summary, GA may exert its inhibitory effect on the proliferative and migratory capacities of OCa cells through suppressing the activity of lncRNA MALAT1/JAK2 axis.

Computational models reveal how chloride dynamics determine the optimal distribution of inhibitory synapses to minimise dendritic excitability

Many neurons in the mammalian central nervous system have complex dendritic arborisations and active dendritic conductances that enable these cells to perform sophisticated computations. How dendritically targeted inhibition affects local dendritic excitability is not fully understood. Here we use computational models of branched dendrites to investigate where GABAergic synapses should be placed to minimise dendritic excitability over time. To do so, we formulate a metric we term the “Inhibitory Level” (IL), which quantifies the effectiveness of synaptic inhibition for reducing the depolarising effect of nearby excitatory input. GABAergic synaptic inhibition is dependent on the reversal potential for GABAA receptors (EGABA), which is primarily set by the transmembrane chloride ion (Cl-) concentration gradient. We, therefore, investigated how variable EGABA and dynamic chloride affects dendritic inhibition. We found that the inhibitory effectiveness of dendritic GABAergic synapses accumulates at an encircled branch junction. The extent of inhibitory accumulation is dependent on the number of branches and location of synapses but is independent of EGABA. This accumulation occurs even for very distally placed inhibitory synapses when they are hyperpolarising – but not when they are shunting. When accounting for Cl- fluxes and dynamics in Cl- concentration, we observed that Cl- loading is detrimental to inhibitory effectiveness. This enabled us to determine the most inhibitory distribution of GABAergic synapses which is close to – but not at – a shared branch junction. This distribution balances a trade-off between a stronger combined inhibitory influence when synapses closely encircle a branch junction with the deleterious effects of increased Cl- loading that occurs when inhibitory synapses are co-located.

Age-related differences in the neural network dynamics underlying the predictability gain

Speech comprehension is often challenged by increased background noise, but can be facilitated via the semantic context of a sentence. This predictability gain relies on an interplay of language-specific semantic and domain-general brain regions. However, age-related differences in the interactions within and between semantic and domain-general networks remain poorly understood. Here we investigated commonalities and differences in degraded speech processing in healthy young and old participants. Participants performed a sentence repetition task while listening to sentences with high and low predictable endings and varying intelligibility. Stimulus intelligibility was adjusted to individual hearing abilities. Older adults showed an undiminished behavioural predictability gain. Likewise, both groups recruited a similar set of semantic and cingulo-opercular brain regions. However, we observed age-related differences in effective connectivity for high predictable speech of increasing intelligibility. Young adults exhibited stronger coupling within the cingulo-opercular network and between a cingulo-opercular and a posterior temporal semantic node. Moreover, these interactions were excitatory in young adults but inhibitory in old adults. Finally, the degree of the inhibitory influence between cingulo-opercular regions was predictive of the behavioural sensitivity towards changes in intelligibility for high predictable sentences in older adults only. Our results demonstrate that the predictability gain is relatively preserved in older adults when stimulus intelligibility is individually adjusted. While young and old participants recruit similar brain regions, differences manifest in network dynamics. Together, these results suggest that ageing affects the network configuration rather than regional activity during successful speech comprehension under challenging listening conditions.

Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals

Background Although electrical stimulation of the peripheral and central nervous systems has attracted much attention owing to its potential therapeutic effects on neuropsychiatric diseases, its non-cell-type-specific activation characteristics may hinder its wide clinical application. Unlike electrical methodologies, optogenetics has more recently been applied as a cell-specific approach for precise modulation of neural functions in vivo, for instance on the vagus nerve. The commonly used implantable optical waveguides are silica optical fibers, which for brain optogenetic stimulation (BOS) are usually fixed on the skull bone. However, due to the huge mismatch of mechanical properties between the stiff optical implants and deformable vagal tissues, vagus nerve optogenetic stimulation (VNOS) in free-behaving animals continues to be a great challenge. Results To resolve this issue, we developed a simplified method for the fabrication of flexible and stretchable polymer optical fibers (POFs), which show significantly improved characteristics for in vivo optogenetic applications, specifically a low Young’s modulus, high stretchability, improved biocompatibility, and long-term stability. We implanted the POFs into the primary motor cortex of C57 mice after the expression of CaMKIIα-ChR2-mCherry detected frequency-dependent neuronal activity and the behavioral changes during light delivery. The viability of POFs as implantable waveguides for VNOS was verified by the increased firing rate of the fast-spiking GABAergic interneurons recorded in the left vagus nerve of VGAT-ChR2 transgenic mice. Furthermore, VNOS was carried out in free-moving rodents via chronically implanted POFs, and an inhibitory influence on the cardiac system and an anxiolytic effect on behaviors was shown. Conclusion Our results demonstrate the feasibility and advantages of the use of POFs in chronic optogenetic modulations in both of the central and peripheral nervous systems, providing new information for the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.

Effect of Molybdate on the Stability of Pit Growth in Duplex Stainless Steel 2205

In the present study, the criteria of pit stabilization and salt formation have been investigated for DSS 2205 using the lead-in-pencil electrode in order to explore the contribution of molybdate in stable pit growth. Results show that the Epit shifts to positive values by increasing molybdate concentration. It is found that the increase in Epit could not be referred to the changes in DCcrit and DCsat, since these values are slightly reduced by adding Molybdate to the solution. In contrast, the active dissolution rate of the metal assessed by idiss,max is hindered in the presence of molybdate ions. Therefore, it is proposed that the mechanism for the inhibitory influence of molybdate can be attributed to an increment in the intersection point of idiss,max/idiff,crit (which reflects Ecrit), and idiss,max/ilim (which reflects Esat). Therefore, increasing the Ecrit and Esat at the pit growth process is responsible for the observed raising of the Epit in presence of Molybdate.

Fulfillment of ESG Responsibilities and Firm Performance: A Zero-Sum Game or Mutually Beneficial

Focusing on the 311 Chinese firms listed in the global markets from 2008 to 2019, based on the trade-off theory and the resource slack theory, using panel vector autoregressive model and panel threshold model, this paper explores the impact of fulfilling ESG responsibility on firm performance. The study reveals that in the short run, fulfilling ESG responsibility presents a “Substitution Effect,” whereas, in the long run, it presents a “Promotional Effect.” On the other hand, the improvement of firm performance has a significantly positive impact on ESG fulfillment investment, even though there is a strong hysteresis effect. Significant heterogeneity exists regarding the relationship between ESG fulfillment and firm performance. ESG fulfillment has a negative impact on firm performance in the short run, with the most affected firms being those small and mid-sized firms listed in the Mainland China markets. In the near term, the impact of firm performance on ESG fulfillment is positive, with those listed in the overseas markets and large firms being affected the most. The study reveals that firm size and the factors affiliated with ESG fulfillment tend to cause the differentiation effect in the inhibitory influence of ESG fulfillment on firm performance in the short run. This study could be used as a guideline for the social responsibilities of nonprofit organizations.

Inhibitory interactions in the system of functionally connected muscles of the shin in patients with the cerebral palsy

In 10 able-bodied individuals and 8 patients with the cerebral palsy reciprocal and non-reciprocal inhibitions of soleus motoneurones were investigated by means of the H-reflex conditioned by electrical stimulation of the tibialis and gastrocnemius medialis nerves, respectively. In normal individuals short- and long-latency periods of both reciprocal and non-reciprocal inhibitions were found. The cerebral palsy patients showed the increased inhibitory influence with more enhanced short-latency components of inhibition. A possible role of inhibitory systems in limitation of patologically activated antigravitant soleus motoneurones was discussed.

Individual Differences in Mental Imagery Modulate Effective Connectivity of Scene-Selective Regions During Resting State

Successful navigation relies on the ability to identify, perceive, and correctly process the spatial structure of a scene. It is well known that visual mental imagery plays a crucial role in navigation. Indeed, cortical regions encoding navigationally relevant information are also active during mental imagery of navigational scenes. However, it remains unknown whether their intrinsic activity and connectivity reflect the individuals’ ability to imagine a scene. Here, we primarily investigated the intrinsic causal interactions among scene-selective brain regions such as Parahipoccampal Place Area (PPA), Retrosplenial Complex (RSC), and Occipital Place Area (OPA) using Dynamic Causal Modelling (DCM) for resting-state functional magnetic resonance (rs-fMRI) data. Second, we tested whether resting-state effective connectivity parameters among scene-selective regions could reflect individual differences in mental imagery in our sample, as assessed by the self-reported Vividness of Visual Imagery Questionnaire (VVIQ). We found an inhibitory influence of occipito-medial on temporal regions, and an excitatory influence of more anterior on more medial and posterior brain regions. Moreover, we found that a key role in imagery is played by the connection strength from OPA to PPA, especially in the left hemisphere, since the influence of the signal between these scene-selective regions positively correlated with good mental imagery ability. Our investigation contributes to the understanding of the complexity of the causal interaction among brain regions involved in navigation and provides new insight in understanding how an essential ability, such as mental imagery, can be explained by the intrinsic fluctuation of brain signal.

Paradoxical facilitation alongside interhemispheric inhibition

Neurophysiological experiments using transcranial magnetic stimulation (TMS) have sought to probe the function of the motor division of the corpus callosum. Primary motor cortex sends projections via the corpus callosum with a net inhibitory influence on the homologous region of the opposite hemisphere. Interhemispheric inhibition (IHI) experiments probe this inhibitory pathway. A test stimulus (TS) delivered to the motor cortex in one hemisphere elicits motor evoked potentials (MEPs) in a target muscle, while a conditioning stimulus (CS) applied to the homologous region of the opposite hemisphere modulates the effect of the TS. We predicted that large CS MEPs would be associated with increased IHI since they should be a reliable index of how effectively contralateral motor cortex was stimulated and therefore of the magnitude of interhemispheric inhibition. However, we observed a strong tendency for larger CS MEPs to be associated with reduced interhemispheric inhibition which in the extreme lead to a net effect of facilitation. This surprising effect was large, systematic, and observed in nearly all participants. We outline several hypotheses for mechanisms which may underlie this phenomenon to guide future research.

Biological effects of iodine, selenium, sulfur citrates in broiler chickens

This study aimed at the assessment of the I, Se, S citrate effect on the organism of broiler chickens. Feeding of chickens of all groups was carried out by using standard balanced feeds – starter, grower, and finish with the use of group feeders placed at the appropriate height from the floor depending on the poultry height. For the chickens of experimental groups, I, Se, S citrate was added to drinking water daily during the 48th day. To the drinking water of chickens of experimental groups different amounts of the citrate solution were added I (200 mg/L), Se (50 mg/L), S (300 mg/L), prepared by the nanotechnology method. Chickens of the II group received the lowest dose of I, Se, S at the rate of 5 μg I/L, 1.25 μg Se/L, 7.5 μg S/L of drinking water, and for poultry of other experimental groups, it was increased by 2 (III), 4 (IV), 6 (V) and 8 (VI) times compared to II group. Coccidiostat "Kokcisan 12%" (KRKA, Slovenia) was added to the starter and grower feed at the stages of its manufacture in quantities of 0.5 kg/t of feed. Coccidiostat was not added to the final feed. During the 48-day technological period, the clinical condition of the poultry was monitored daily by forage and motor activity, safety, and every 7 days – for growth intensity with the individual determination of body weight on a laboratory scale. The investigation of the blood was carried out from the 35th or 48th day during the growing, period and also investigation of the internal organs – liver, heart, spleen, stomach, thymus, and bursa of Fabricius. The increase of cholesterol, triacylglycerols, and albumin in the blood of II, III, and VI chicken groups was established on the 35th day of the experiment, and the reduction of creatinine in III and VI groups. By that time, the effect of highest dose of I, Se, S caused a decrease in the T3 concentration in the blood of chickens in the VI group compared to the I and II groups. In particular, in the blood of chickens of IV, V and VI groups compared to the I, II, III group under these conditions there was a significant increase in the content of urea, Ca, P, cholesterol, as well as albumin – only in IV group on the 48th day. Triacylglycerols’ content increased in the blood serum of chickens in III and IV groups compared to the II and V groups, but in V group – decreased compared to the III, IV groups. The increase in liver, thymus, and heart mass in the II and V chicken groups was noticed and their decrease in the VI group was revealed compared with the control group. Reliable lower coefficients of the body mass of chickens of III and VI groups may indicate a less notable stimulating biological effect of I, Se, S citrate in these doses on liver development than on the whole organism. The addition of I, Se, S citrate to broiler chickens during the period of growing revealed the difference in their biological action in the presence and absence of the Kokcisan 12% in a mixed fodder. A more notable stimulating effect of low dose of I, Se, S citrate on the growth and development on the chickens' organism was established during the withdrawal of coccidiostatics from their diet. The effect may be due to its inhibitory influence on the biological activity of these elements in the first 35 days of growing. In the final period of chicken growing and withdrawal of ionophore Kokcisan from the diet more noticeable changes were revealed in the studied parameters.