Significant Stimulatory Effect Research Articles

Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis.

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

Impact of theta transcranial alternating current stimulation on language production in adult classic galactosemia patients.

Patients with classic galactosemia (CG), an inborn error of galactose metabolism, suffer from impairments in cognition, including language processing. Potential causes are atypical brain oscillations. Recent electroencephalogram (EEG) showed differences in the P300 event-related-potential (ERP) and alterations in the alpha/theta-range during speech planning. This study investigated whether transcranial alternating current stimulation (tACS) at theta-frequency compared to sham can cause a normalization of the ERP post stimulation and improves language performance. Eleven CG patients and fourteen healthy controls participated in two tACS-sessions (theta 6.5 Hz/sham). They were engaged in an active language task, describing animated scenes at three moments, that is, pre/during/post stimulation. Pre and post stimulation, behavior (naming accuracy, voice-onset-times; VOT) and mean-amplitudes of ERP were compared, by means of a P300 time-window analysis and cluster-based-permutation testing during speech planning. The results showed that theta stimulation, not sham, significantly reduced naming error-percentage in patients, not in controls. Theta did not systematically speed up naming beyond a general learning effect, which was larger for the patients. The EEG analysis revealed a significant pre-post stimulation effect (P300/late positivity), in patients and during theta stimulation only. In conclusion, theta-tACS improved accuracy in language performance in CG patients compared to controls and altered the P300 and late positive ERP-amplitude, suggesting a lasting effect on neural oscillation and behavior.

Impact of coconut kernel extract on carcinogen-induced skin cancer model: Oxidative stress, C-MYC proto-oncogene and tumor formation

This study aimed at analysing the effects of coconut (Cocos nucifera L.) kernel extract (CKE) on oxidative stress, C-MYC proto-oncogene, and tumour formation in a skin cancer model. Tumorigenesis was induced by dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA). In vitro antioxidant activity of CKE was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), total phenolic and flavonoid content assays. CKE showed a higher antioxidant activity then ascorbic acid (*P < 0.05, ****P < 0.0001). HPLC and NMR study of the CKE revealed the presence of lauric acid (LA). Following the characterization of CKE, mice were randomly assigned to receive DMBA/TPA Induction and CKE treatment at different doses (50, 100, and 200 mg/kg) of body weight. LA 100 mg/kg of body weight used as standard. Significantly, the CKE200 and control groups' mice did not develop tumors; however, the CKE100 and CKE50 treated groups did develop tumors less frequently than the DMBA/TPA-treated mice. Histopathological analysis revealed that the epidermal layer in DMBA-induced mice was thicker and had squamous pearls along with a hyperplasia/dysplasia lesion, indicating skin squamous cell carcinoma (SCC), whereas the epidermal layers in CKE200-treated and control mice were normal. Additionally, the CKE treatment demonstrated a significant stimulatory effect on the activities of reactive oxygen species (ROS), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), as well as an inhibitory effect on lipid peroxidase (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001) and c-MYC protein expression (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001). In conclusion, CKE prevents the growth of tumors on mouse skin by reducing oxidative stress and suppressing c-MYC overexpression brought on by DMBA/TPA induction. This makes it an effective dietary antioxidant with anti-tumor properties.

Evaluation of immunomodulatory potential of probiotic conditioned medium on murine macrophages

Probiotics are a mixture of beneficial live bacteria and/or yeasts that naturally exist in our bodies. Recently, numerous studies have focused on the immunostimulatory effects of single-species or killed multi-species probiotic conditioned mediums on macrophages. This study investigates the immunostimulatory effect of commercially available active, multi-species probiotic conditioned medium (CM) on RAW264.7 murine macrophages. The probiotic CM was prepared by culturing the commercially available probiotic in a cell-culture medium overnight at 37 °C, followed by centrifugation and filter-sterilization to be tested on macrophages. The immunostimulatory effect of different dilution percentages (50%, 75%, 100%) of CM was examined using the MTT assay, proinflammatory cytokine (tumor necrosis factor TNF-alpha) production in macrophages, migration, and phagocytosis assays. For all the examined CM ratios, the percentages of cell viability were > 80%. Regarding the migration scratch, TNF-alpha and phagocytosis assays, CM demonstrated a concentration-dependent immunostimulatory effect. However, the undiluted CM (100%) showed a significant (p-value < 0.05) stimulatory effect compared to the positive and negative controls. The findings suggest that the secretions and products of probiotics, as measured in the CM, may be closely associated with their immune-boosting effects. Understanding this relationship between probiotic secretions and immune function is crucial for further exploring the potential benefits of probiotics in enhancing overall health and well-being.

The Effect of Simple Drawing Stimulation on Hand-Eye Coordination in 7-8 Years Children with Mental Retardation in Banyumas Regency

Background : The development of hand-eye coordination in children with mental retardation duffers from that of typically developing children. Stimulation is needed to enhance the development of hand-eye coordination. Objective : To prove the effect of simple drawing stimulation on hand-eye coordination in children with mental retardation aged 7-8 years in Banyumas regency. Methods : This quantitative research used a quasi-eksperimental designs with a non-equivalent control group. The respondents in study were children with mental retardation aged 7-8 years in Banyumas regency. The sample cosisted of 32 children, with 16 children in experiment group and 16 in control group, selected using the total sampling technique. Results : Most children with mental retardation had Down Syndrome, accounting for 13 (41%) out of 32 children. Based on the level of mental retardation, mild mental retardation was the most common, with 20 (63%) out of 32 children. Most children were 7 years old, totaling 19 (59%) and the majority were male, with 22 (69%). The results of this study show a significant effect of simple drawing stimulation on hand-eye coordination os indicated by paired sample t-test for both experimental group (0,005) and the control group (0,001) (p ? 0.005). The independent sampel test also yielded a significant value (0,121) (p ? 0,005). Conclusion : Simple drawing stimulation affects the development of hand-eye coordination with a significant value 0,001 (p ? 0.005).

Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial.

Progressive supranuclear palsy (PSP) is a rare 4R-tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms. This randomized, double-blinded, sham-controlled trial aimed at verifying the short-, mid-, and long-term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP. Twenty-five patients were randomly assigned to active or sham stimulation (2 mA for 20 minute) for 5 days/week for 2 weeks. Participants underwent assessments at baseline, after the 2-week stimulation protocol, then after 45 days and 3 months from baseline. Primary outcomes were verbal and semantic fluency. The efficacy was verified with analysis of covariance. We failed to detect a significant effect of active stimulation on primary outcomes. Stimulation was associated to worsening of specific behavioral complaints. A 2-week protocol of anodal left DLPFC tDCS is not effective in PSP. Specific challenges in running symptomatic clinical trials with classic design are highlighted. © 2024 International Parkinson and Movement Disorder Society.

Polystyrene microplastics promote intestinal colonization of Aeromonas veronii through inducing intestinal microbiota dysbiosis

The premise that pathogen colonized microplastics (MPs) can promote the spread of pathogens has been widely recognized, however, their role in the colonization of pathogens in a host intestine has not been fully elucidated. Here, we investigated the effect of polystyrene MPs (PS-MPs) on the colonization levels of Aeromonas veronii, a typical aquatic pathogen, in the loach (Misgurnus anguillicaudatus) intestine. Multiple types of MPs were observed to promote the intestinal colonization of A. veronii, among which PS-MPs exhibited the most significant stimulating effect (67.18% increase in A. veronii colonization). PS-MPs inflicted serious damage to the intestinal tracts of loaches and induced intestinal microbiota dysbiosis. The abundance of certain intestinal bacteria with resistance against A. veronii colonization decreased, with Lactococcus sp. showing the strongest colonization resistance (73.64% decline in A. veronii colonization). Fecal microbiota transplantation was performed, which revealed that PS-MPs induced intestinal microbiota dysbiosis was responsible for the increased colonization of A. veronii in the intestine. It was determined that PS-MPs reshaped the intestinal microbiota community to attenuate the colonization resistance against A. veronii colonization, resulting in an elevated intestinal colonization levels of A. veronii.

Surface display system of Bacillus subtilis: A promising approach for improving the stability and applications of cellobiose dehydrogenase

Cellobiose dehydrogenase (CDH) plays a crucial role in lignocellulose degradation and bioelectrochemical industries, making it highly in demand. However, the production and purification of CDH through fungal heterologous expression methods is time-consuming, costly, and challenging. In this study, we successfully displayed Pycnoporus sanguineus CDH (psCDH) on the surface of Bacillus subtilis spores for the first time. Enzymatic characterization revealed that spore surface display enhanced the tolerance of psCDH to high temperature (80 °C) and low pH levels (3.5) compared to free psCDH. Furthermore, we found that glycerol, lactic acid, and malic acid promoted the activity of immobilized spore-displayed psCDH; glycerol has a more significant stimulating effect, increasing the activity from 16.86 ± 1.27 U/mL to 46.26 ± 3.25 U/mL. After four reuse cycles, the psCDH immobilized with spores retained 48% of its initial activity, demonstrating a substantial recovery rate. In conclusion, the spore display system, relying on cotG, enables the expression and immobilization of CDH while enhancing its resistance to adverse conditions. This system demonstrates efficient enzyme recovery and reuse. This approach provides a novel method and strategy for the immobilization and stability enhancement of CDH.

Особенности режима обжалования определений судов в гражданском судопроизводстве

The work is devoted to the study of legislative and law enforcement restrictions on challenging individual court rulings. It has been established that legal facts, including deadlines, and subjective rights are used as means of legal regimes in this case, in particular. These funds have a significant stimulating or disincentive effect on participants in the proceedings. In addition, the lack of legal regulation may have an impact on the participants in the process. As an example, the article considers the appeal of the ruling on the abandonment of the statement of claim without motion and on the transfer of the case by jurisdiction. The author comes to the conclusion that today there is a regime of unfavorable appeal of court rulings. As a result, there are abuses of the participants in the process, red tape on the part of the court. The solution to these problems is the establishment of disciplining and enforceable deadlines on the part of the participants, taking into account the interests of the participants in the formulation of their rights, as well as individual legal structures.

Refinement of Drug Regulation and Russian Pharmaceutical Export

Strategy on development of the pharmaceutical industry for the period up to 2030 (Pharma-2030 Strategy), adopted in the Russian Federation this year, includes tasks to further saturate the national market with domestic medicines and to “realize the export potential of the pharmaceutical industry”. National drug regulation has a significant stimulating effect on the export of medicines. To identify the most important elements of this regulation related to the development and maintenance of sustainable pharmaceutical export, different aspects of national drug regulatory systems were studied. Countries belonging to different segments of the global pharmaceutical export market were included in the research. The results of the analysis of drug regulation in top export countries were published earlier. This article presents the results for pharmerging countries with a fastgrowing pharmaceutical sector and formulated common strategies for these countries that are aimed at achieving leadership positions of the national pharmaceutical industry in both the domestic and foreign markets. Several measures have been proposed for inclusion in the implementation plan for the Pharma-2030 Strategy, which, in our opinion, will contribute to achieving the goals set both to stimulate exports and to saturate the Russian market with domestic medicines.

Characteristics of Stenotrophomonas rhizophila Lipopolysaccharide, a Representative of Antarctica

Characteristics of Stenotrophomonas rhizophila Lipopolysaccharide, a Representative of Antarctica

Evidence of the Beneficial Impact of Three Probiotic-Based Food Supplements on the Composition and Metabolic Activity of the Intestinal Microbiota in Healthy Individuals: An Ex Vivo Study.

Scientific evidence has increasingly supported the beneficial effects of probiotic-based food supplements on human intestinal health. This ex vivo study investigated the effects on the composition and metabolic activity of the intestinal microbiota of three probiotic-based food supplements, containing, respectively, (1) Bifidobacterium longum ES1, (2) Lactobacillus acidophilus NCFM®, and (3) a combination of L. acidophilus NCFM®, Lactobacillus paracasei Lpc-37™, Bifidobacterium lactis Bi-07™, and Bifidobacterium lactis Bl-04™. This study employed fecal samples from six healthy donors, inoculated in a Colon-on-a-plate® system. After 48 h of exposure or non-exposure to the food supplements, the effects were measured on the overall microbial fermentation (pH), changes in microbial metabolic activity through the production of short-chain and branched-chain fatty acids (SCFAs and BCFAs), ammonium, lactate, and microbial composition. The strongest effect on the fermentation process was observed for the combined formulation probiotics, characterized by the significant stimulation of butyrate production, a significant reduction in BCFAs and ammonium in all donors, and a significant stimulatory effect on bifidobacteria and lactobacilli growth. Our findings suggest that the combined formulation probiotics significantly impact the intestinal microbiome of the healthy individuals, showing changes in metabolic activity and microbial abundance as the health benefit endpoint.

Modulating risk-taking behavior with theta-band tACS

Although risk is prevalent in decision-making, the specific neural processes underlying risk-taking behavior remain unclear. Previous studies have suggested that frontal theta-band activity plays a crucial role in modulating risk-taking behavior. The functional relevance of theta in risk-taking behavior is yet to be clearly established and studies using noninvasive brain stimulation have yielded inconsistent findings. We aimed to investigate this relevance using transcranial alternating current stimulation (tACS) over right or left dorsolateral prefrontal cortex (DLPFC). We also studied the influence of stimulation intensity on risk-taking behavior and electrophysiological effects.We applied theta-band (6.5 Hz) tACS over the left (F3) and right (F4) DLPFC with lower (1.5 mA) and higher (3 mA) tACS intensities. We employed a single-blinded, sham-controlled, within-subject design and combined tACS with electroencephalography (EEG) measurements and the Maastricht Gambling Task (MGT) to elicit and evaluate risk-taking behavior.Our results show an increase in risk-taking behavior after left DLPFC stimulation at both intensities and a reduction of risk-taking behavior after 3 mA (and not 1.5 mA) right DLPFC stimulation compared to sham. Further analyses showed a negative correlation between resting-state frontal theta-power and risk-taking behavior. Overall, frontal theta-power was increased after left, but not right, theta-band tACS independent of stimulation intensity.Our findings confirm the functional relevance of frontal theta-band activity in decision-making under risk and the differential role of left and right DLPFC. We also were able to show that stimulation intensity did have an effect on behavioral responses, namely risk-taking behavior. Significant right hemisphere stimulation effects were observed only after high-intensity stimulation. Nevertheless, electrophysiological effects were only significant after left DLPFC stimulation, regardless of tACS intensity. Furthermore, the results indicate the role of the baseline frontal theta-power in the direction of behavioral effects after theta-band tACS.

Naphthaleneoxypropargyl-Containing Piperazine as a Regulator of Effector Immune Cell Populations upon an Aseptic Inflammation.

This study investigated the effects of aseptic inflammation and heavy metal exposure on immune responses, as well as the potential immunomodulatory properties of the newly synthesized 1-[1-(2,5-dimethoxyphenyl)-4-(naphthalene-1-yloxy)but-2-ynyl]-4-methylpiperazine complexed with β-cyclodextrin (β-CD). Aseptic inflammation was induced by a subcutaneous injection of turpentine in rats, while heavy metal exposure was achieved through a daily administration of cadmium chloride and lead acetate. The levels of immune cell populations, including cytotoxic T lymphocytes (CTL), monocytes, and granulocytes, were assessed in the spleen. The results showed that aseptic inflammation led to decreased levels of CTL, monocytes, and granulocytes on the 14th day, indicating an inflammatory response accompanied by a migration of effector cells to the inflamed tissues. The exposure to cadmium chloride and lead acetate resulted in systemic immunotoxic effects, with reduced levels of B cells, CD4+ Th cells, monocytes, and granulocytes in the spleen. Notably, piperazine complexed with β-CD (the complex) exhibited significant stimulatory effects on CD4+, CD8+, and myeloid cell populations during aseptic inflammation, even in the presence of heavy metal exposure. These findings suggest the potential immunomodulatory properties of the complex in the context of aseptic inflammation and heavy metal exposure.

Effects of anodal tDCS on electroencephalography correlates of cognitive control in mild-to-moderate traumatic brain injury.

Transcranial direct current stimulation (tDCS) may provide a potential therapy for cognitive deficits caused by traumatic brain injury (TBI), yet its efficacy and mechanisms of action are still uncertain. We hypothesized that anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) would boost the influence of a cognitive training regimen in a mild-to-moderate TBI (mmTBI) sample. Cognitive enhancement was measured by examining event-related potentials (ERPs) during cognitive control tasks from pre- to post-treatment. Thirty-four participants with mmTBI underwent ten sessions of cognitive training with active (n = 17) or sham (n = 17) anodal tDCS to the left DLPFC. ERPs were assessed during performance of an auditory oddball (3AOB), N-back, and dot pattern expectancy (DPX) task before and after treatment. P3b amplitudes significantly decreased from baseline to post-treatment testing, regardless of tDCS condition, in the N-back task. The active tDCS group demonstrated a significantly increased P3a amplitude in the DPX task. No statistically significant stimulation effects were seen during the 3AOB and N-back tasks. Active anodal tDCS paired with cognitive training led to increases in P3a amplitudes in the DPX, inferring increased cognitive control. P3b decreased in the N-back task demonstrating the effects of cognitive training. These dissociated P3 findings suggest separate mechanisms invoked by different neuroplasticity-inducing paradigms (stimulation versus training) in brain networks that support executive functioning.

Effect of Binaural Beat Stimulation on Auditory and Visual Sustained Attentions in Young People with Normal Hearing

Background and Aim: Numerous studies have investigated the effect of binaural beat stimulation on visual attention. In this study, we aim to investigate the effect of binaural beats on both auditory and visual sustained attention of young people with normal hearing.&#x0D; Methods: Thirty normal-hearing people with mean age of 27.77±6.85 years were divided into two groups of Sham-Binaural beat (SB, n=15) and Binaural beat-Sham (BS, n=15). The participants in each group performed the Integrated Visual and Auditory-2 Continuous Performance Test (IVA-2 CPT) twice on different days. The SB group performed the IVA-2 CPT first under sham condition and then in the presence of binaural beats. In the BS group, the order was reversed in terms of stimuli presentation. The binaural beat stimulus was an audio file that induced beats at a frequency of 16 Hz by presenting 400 and 416 Hz stimuli to the right and left ears, respectively. The sham stimulus was a pure tone of 400 HZ. A mixed analysis of variance (ANOVA) was used to compare the means.&#x0D; Results: The results showed the significant effect of binaural beat stimulation on auditory sustained attention (p&lt;0.001). However, its effect on visual sustained attention was not significant (p=0.061).&#x0D; Conclusion: Stimulation with binaural beats of 16 Hz may improve the auditory sustained attention in young people with normal hearing. It cannot improve their visual sustained attention.&#x0D; Keywords: Binaural beat stimulation; visual; auditory; sustained attention

Ginsenoside Rg1 alleviates ANIT-induced cholestatic liver injury by inhibiting hepatic inflammation and oxidative stress via SIRT1 activation

Ethnopharmacological relevanceGinseng (Panax ginseng C. A. Mey) is a common traditional Chinese medicine used for anti-inflammation, treating colitis, type 2 diabetes, diarrhea, and recovering hepatobiliary function. Ginsenosides, the main active components isolated from ginseng, possess liver and gallbladder diseases therapeutic potential. Aims of the studyCholestatic liver injury (CLI) is a liver disease induced by intrahepatic accumulation of toxic bile acids and currently lacks clinically effective drugs. Our previous study found that ginsenosides alleviated CLI by activating sirtuin 1 (SIRT1), but the effective ingredients and the underlying mechanism have not been clarified. This study aimed to identify an effective ingredient with the most significant activation effect on SIRT1 from the five major monomer saponins of ginsenosides: Rb1, Rd, Rg1, 20s-Rg3, and Rc further explore its protective effects on CLI, and elaborate its underlying mechanism. Materials and methodsDiscovery Studio 3.0 was used to conduct molecular docking between monomer saponins and SIRT1, and further detect the influence of monomer saponins on SIRT1 activity in vitro. Finally, it was determined that Rg1 had the most significant stimulative effect on SIRT1, and the hepatoprotective activity of Rg1 in CLI was explored in vivo. Wild-type mice were intragastrically α-naphthylisothiocyanate (ANIT) to establish an experimental model of intrahepatic cholestasis and Rg1 intervention, and then liver injury and cholestasis related indexes were detected. In addition, Liver-specific SIRT1 gene knockout (SIRT1-/-) mice were administered with ANIT and/or Rg1 to further investigate the mechanism of action of Rg1. ResultsThe results of molecular docking and in vitro experiments showed that all the five ginsenoside monomers could bind to the active site of SIRT1 and promote SIRT1 activity in HepG2 cells. Among them, Rg1 exhibited the most significant stimulation of SIRT1 activity in cholestasis. Besides, it could ameliorate ANIT-induced inflammation and oxidative stress in HepG2 cells. Therefore, we investigated the hepatoprotective effect and mechanism of Rg1 on CLI. Results showed that Rg1 reversed the ANIT-induced increase in biochemical parameters, improved liver pathological injury, and decreased liver lipid accumulation, reactive oxygen species and pro-inflammatory factor levels. Mechanistically, Rg1 induced SIRT1 expression, followed by promoted the activity of Nrf2 and suppressed the activation of NF-κB. Interestingly, the hepatoprotective effect of Rg1 was blocked in SIRT1-/- mice. ConclusionRg1 mitigated ANIT-induced CLI via upregulating SIRT1 expression, and our results suggested that Rg1 is a candidate compound for treating CLI.

The Immunostimulatory Effect of Probiotic Conditioned Medium on RAW264.7 Murine Macrophages

Background: Probiotics are a mixture of good live bacteria and/or yeasts that naturally survive in our bodies. Recently, loads of studies have focused on their role in the immune system and digestive tract. Accordingly, there are many commercially available probiotic products in the market. This study examines the immunostimulatory effect of commercially available-probiotic conditioned medium (PCM) on RAW264.7 murine macrophages.&#x0D; Methods: Probiotic conditioned medium has been prepared by culturing the commercially available probiotic in a cell culture medium overnight at 37°C, followed by centrifugation and filter-sterilization to be tested on RAW264.7 murine macrophages. The immunostimulatory effect of different ratios (50, 75, 100) of PCM was examined using MTT assay, pro-inflammatory cytokine (tumor necrosis factor TNF-alpha) production in macrophages., migration, and Phagocytosis assays.&#x0D; Results: At all the examined PCM ratios, the percentages of cell viability were &gt;80%. Regarding the migration scratch, TNF-alpha and phagocytosis assays, PCM demonstrated a concentration-dependent pattern in the immunostimulatory effect. However, the ratio of 100 PCM illustrated a significant (p-value&lt;0.05) stimulatory effect compared to the positive and negative control.&#x0D; Conclusion: The findings of this study confirm the stimulatory activity of probiotic conditioned medium, which may contribute directly to the immune-boosting effect of the probiotic supplements.

Simulation of the Damage and Failure Characteristics of Coal under True Triaxial Static–Dynamic Loads

The damage evolution rules for coal under true triaxial combined static–dynamic loads are important to understand and reveal the mechanism of rockburst in coal mines. The numerical simulation was carried out using FLAC3D to explore the coupling effect of static and dynamic stress, especially the influence of dynamic load parameters. The results show that the increase in dynamic load amplitude not only makes the plastic zone grow exponentially and shortens the damage development time, but also decreases the residual strength of the coal sample, which leads to a much more violent dynamic failure. The stress wave propagation can be more stable in the coal sample with the increase in dynamic load frequency and the development time of the plastic zone also shows synchronous fluctuating features, and when the frequency is like the intrinsic frequency of the coal sample, the dynamic load has a significant stimulation effect. The static and dynamic loads have different damage effects on the coal sample under the true triaxial stress path, the weight decreases in descending order, namely the minimum principal stress, the maximum principal, the amplitude of the dynamic load and, lastly, the dynamic stress frequency, according to the entropy weight method analysis.

Human preterm colostrum stimulates outgrowth in neurogenic tissue

BackgroundThe olfactory bulb has a key role for nasal delivery of drugs to the brain by its access from the nasal mucosa and its connection to the subventricular zone. The aim of this study was to investigate the neuromodulatory capacity of human milk of premature infants on the olfactory bulb.MethodsOlfactory bulbs from P1 mice were embedded in a collagen I gel and incubated with DMEM supplemented with the aqueous phase of human colostrum (Col) of five mothers after very preterm birth, mature milk (Mat) of the same mothers or without supplement (Ctrl). After 7 days, the neurite outgrowth was quantified. Proteome analysis of the milk samples was performed using unlabeled mass spectrometry.ResultsOutgrowth increased significantly in bulbs exposed to Col but not when exposed to Mat. Mass spectrometry revealed profound differences in the proteome of Col versus Mat. Among 21 upregulated proteins in Col were proteins involved in neurite outgrowth, axon guidance, neuromodulation and longevity.ConclusionsA high bioactivity of human preterm colostrum on murine neonatal neurogenic tissue is demonstrated to be associated with a proteome profoundly differing from mature milk.ImpactThe hypothesis has been raised that neonatal brain damage in a preterm infant could potentially be ameliorated by intranasal application of maternal breast milk.In an in-vitro model using neonatal murine olfactory bulb explants a significant stimulatory effect by human preterm colostrum is observed.Proteomics reveals upregulated neuroactive proteins in human colostrum compared to mature milk.A confirmation of this exploratory study would indicate that preterm colostrum stimulates neurogenic tissue.Early intranasal colostrum application might attenuate perinatal loss of neurogenic tissue thereby contributing to reducing complications such as cerebral palsy.