Stimulatory Effect Research Articles

Pleiotrophin Activates cMet- and mTORC1-Dependent Protein Synthesis through PTPRZ1-The Role of ανβ3 Integrin.

Pleiotrophin (PTN) is a secreted factor that regulates endothelial cell migration through protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) and αvβ3 integrin. Genetic deletion of Ptprz1 results in enhanced endothelial cell proliferation and migration, due to the decreased expression of β3 integrin and the subsequent, enhanced cMet phosphorylation. In the present study, we investigated the effect of PTN and PTPRZ1 on activating the mTORC1 kinase and protein synthesis and identified part of the implicated signaling pathway in endothelial cells. PTN or genetic deletion of Ptprz1 activates protein synthesis in a mTORC1-dependent manner, as shown by the enhanced phosphorylation of the mTORC1-downstream targets ribosomal protein S6 kinase 1 (SK61) and 4E-binding protein 1 (4EBP1) and the upregulation of HIF-1α. The cMet tyrosine kinase inhibitor crizotinib abolishes the stimulatory effects of PTN or PTPRZ1 deletion on mTORC1 activation and protein synthesis, suggesting that mTORC1 activation is downstream of cMet. The mTORC1 inhibitor rapamycin abolishes the stimulatory effect of PTN or PTPRZ1 deletion on endothelial cell migration, suggesting that mTORC1 is involved in the PTN/PTPRZ1-dependent cell migration. The αvβ3 integrin blocking antibody LM609 and the peptide PTN112-136, both known to bind to ανβ3 and inhibit PTN-induced endothelial cell migration, increase cMet phosphorylation and activate mTORC1, suggesting that cMet and mTORC1 activation are required but are not sufficient to stimulate cell migration. Overall, our data highlight novel aspects of the signaling pathway downstream of the PTN/PTPRZ1 axis that regulates endothelial cell functions.

Electrochemistry enhanced multi-stage biological contact oxidation treating sulfamethoxazole wastewater: Performance, degradation pathway and microbial community

Clean and economical techniques are in urgent need for improving antibiotics removal from wastewater. In this study, a multi-stage bio-contact oxidation reactor (BCOR) was constructed and further enhanced by electrochemistry to treat sulfamethoxazole (SMX) wastewater. The stimulatory effects of the electrochemistry were investigated together with the succession of microbial communities as well as the possible conversion pathways of SMX. The results showed that the SMX and chemical oxygen demand removal rates reached up to 92.96 ± 0.62 % and 91.42 ± 0.82 % at electric current density of 2.0 mA/cm2. Electrochemistry enhancement induced bone cleavage and oxidation transformation pathways of SMX while reduced the toxicity of degrading intermediates. Moreover, electrochemistry enhancement stimulated the growth of Klebsiella and Rhodobacter as well as the fermentation, chemoheterotrophy and aerobic_chemoheterotrophy functions which further promoted the SMX removal. This study revealed the biochemical removal mechanisms of SMX degradation and manifested the feasibility of combing electrochemistry with BCOR to treat antibiotics wastewater with low energy consumption.

Preliminary Studies on the Effect of Soil Conditioner (AMP) Application on the Chemical and Microbiological Properties of Soil under Winter Oilseed Rape Cultivation

This study analyzed the effect of the application of a soil conditioner under the trade name of the Agro Mineral Product (AMP) in the winter rapeseed cultivation on the bacterial and fungal abundance, ion concentrations, and electrolytic conductivity of the soil solution. It was demonstrated that the AMP influenced changes in the total abundance of the culturable fractions of the soil bacteria and fungi at each of the tested time points. A stimulatory effect of the preparation on the growth of the soil bacteria and an inhibitory effect on the development of the fungi was observed, particularly at doses of 4 and 8 t·ha−1. A dose of 12 t·ha−1 proved to be the least effective in relation to the development of the soil microbiome. Increasing the AMP fertilization dose above 4 t·ha−1 caused changes in the chemistry of the soil solution (pH, EC, HCO3−, K+, and PO4-P). It is worth noting that this primarily resulted in decreases in the amounts of mobile forms of potassium (from 40.4 mg·dm−3 in the control to 26.7 mg·dm−3 at the 8 t·ha−1 dose) and orthophosphate as phosphorus (from −6.00 mg·dm−3 in the control to 3.75 mg·dm−3 at the 8 t·ha−1 dose) in the soil solution, which resulted in a reduction in the yield of the winter rapeseed (from 4.76 t·ha−1 in the control to 4.61 t·ha−1 at the 8 t·ha−1 and 4.43 t·ha−1 at the 12 t·ha−1 AMP dose).

Protective Effect of Lavandula officinalis on Pentylenetetrazol-Induced Epilepsy in Mice: Expression of NOS Genes and Caspase-3

Abstract Objective Given the incidence of epilepsy and the adverse effects of unconventional antiepileptic medicines, there is a need for a novel medical treatment strategy for epileptic patients. Material and Methods The current study involved the selection of 80 male mice, which were then separated into 10 experimental groups: pentylenetetrazol (PTZ), negative control which received normal saline, treatment which received Lavandula officinalis in two doses of 200 and 400 mg/kg, L. officinalis 200 mg/kg and 1400 w, L. officinalis 200 mg/kg and 7-NI, L. officinalis 200 mg/kg and diphenylene iodonium chloride (DPI), L. officinalis 400 mg/kg and 1400 w, L. officinalis 400 mg/kg and 7-nitroindazole (7-NI) and group which received L. officinalis 400 mg/kg and DPI. Each group was stimulated with an 11-day injection cycle (every 48 hours) of PTZ at a dosage of 35 mg/kg. All groups underwent PTZ challenge dosage (75 mg/kg) testing during the 12th injection. Ultimately, the brains of all mice were extracted, and the activity of genes related to neuronal nitric oxide, inducible nitric oxide, and endothelial nitric oxide was assessed. The enzyme-linked immunosorbent assay (ELISA) method was used to assess the quantity of caspase-3 in the groups. Results Lavandula officinalis decreased the severity of seizures. The findings of our study demonstrated that the extract had a suppressive effect on the expression of inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS; p < 0.05), while it had a stimulatory effect on endothelial NOS (eNOS; p < 0.05). In addition, L. officinalis reduced caspase-3 levels in the groups who were administered the extract. Conclusion The hydroalcoholic extract of L. officinalis has been found to be effective. Lavandula officinalis enhanced the expression of endothelial nitric oxide and reduced the levels of neuronal and inducible nitric oxide to a greater extent in brain tissue affected by epilepsy. The groups receiving extract derived from L. officinalis exhibited a reduction in the level of caspase-3.

7609 Androgen Receptor Positive DCIS in a Transmasculine Individual on Testosterone Therapy

Abstract Disclosure: J. Kelly: None. B. Cohen: None. Introduction: The rate of breast cancer in transgender men is lower than in cisgender women, perhaps due to lower estrogen levels in the setting of suppression from exogenous testosterone, lack of clear guidelines on screening after top surgery, and increase in mastectomies. However, the impact of testosterone therapy on existing breast cancer is not known. Concerns regarding use of testosterone in patients with breast cancer include the potential for conversion of testosterone to estradiol, as well as direct androgen receptor (AR) stimulation. However, for some patients, hormone therapy is lifesaving and stopping gender affirming hormone therapy (GAHT) will negatively impact patient well-being. This creates a challenging clinical scenario when transgender patients on testosterone are diagnosed with breast cancer.Case Presentation: We present a case of a 29-year-old self-identified transmasculine nonbinary individual (assigned female at birth) who underwent chest reconstruction surgery after several months on daily transdermal testosterone therapy. A 4 cm DCIS ER+/AR+ with possible micro invasion was incidentally noted on pathology. They had no family history of breast cancer. The patient underwent chest MRI which was negative for persistent disease. The treating oncologist did not recommend Tamoxifen. The patient chose to discontinue testosterone therapy due to uncertainty regarding future breast cancer risk. However, due to worsening depression and fatigue, the patient chose to resume GAHT after receiving counseling of possible risk, though likely low, of cancer recurrence. Given that they had undergone bilateral mastectomy which, unlike chest reconstruction surgery where some breast tissue is left for contouring, all breast tissue was removed and given that chest MRI was negative for disease, cancer recurrence was felt to be low. Furthermore, though AR positivity was noted, the clinical implications are unclear and it is not known whether testosterone would stimulate tumor growth or potentially have antagonistic effects on ER signaling. Additionally, any stimulatory effects of AR signaling may be balanced by androgen suppression of gonadotroph production and reduction in estrogen production; this is more clearly associated with stimulatory effects on cancer growth. And finally, the potential risks of therapy must be weighed against the benefits provided to the patient’s well-being and mental health. Ultimately, the patient resumed testosterone therapy and has been doing well.Teaching Point: This case illustrates the uncertainties regarding the management of gender affirming testosterone therapy in patients with DCIS or breast cancer. It also highlights the need for a patient centered approach to decisions regarding changes to GAHT, to appropriately weigh the risks and benefits of continuing therapy. Presentation: 6/2/2024

8595 Brain Penetration Impedes SERD Efficacy in Breast Cancer Pre-clinical Models

Abstract Disclosure: S.E. Wardell: None. B. Chakraborty: None. S. Artham: None. M.A. Newlin: None. M. Kirkland: None. C. Chang: None. D.P. McDonnell: None. Most breast cancers express the estrogen receptor (ER, ESR1), and agents that target ER remain the cornerstone of interventions used to treat this disease at all stages. Aromatase inhibitors (AI), which block estrogen synthesis, and the selective ER downregulator (SERD) fulvestrant were developed with the goal of achieving absolute inhibition of ER signaling in tumors. However, it has been assumed that the clinical efficacy (and utility) of fulvestrant is somewhat limited by its poor pharmaceutical properties and the requirement that it be administered by intramuscular injection. This, together with the observation that the activating ESR1 mutations selected for during AI treatment are not effectively inhibited by fulvestrant, encouraged the development of new classes of SERDs that achieve sufficient exposure to saturate and degrade ER in tumors. The recent approval of the second-generation SERD elacestrant for the treatment of breast cancers harboring ESR1 mutations was a major advance in approaches to target ER in advanced breast cancer. Several additional oral SERDs have been developed and evaluated as potential treatments for advanced metastatic breast cancer. Despite showing substantial efficacy in pre-clinical assays that assess ER downregulation and gene transcription, and notably equivalent antitumor activities in cell line derived and PDX tumors in immunocompromised mice, the clinical development of the majority of these SERDs has been discontinued for lack of efficacy. In reviewing the available clinical data across many SERD programs, we noted that some drugs demonstrated a paradoxical, non-linear response curve with higher doses exhibiting less efficacy than lower doses. Probing this pharmacology in animal models we determined that the ability of SERDs to cross the blood brain barrier and attenuate ER signaling in the hypothalamus was a key differentiator of SERDs. In validated syngeneic models of breast cancer, we observed doses of fulvestrant having confirmed brain exposure stimulated tumor growth independent of tumor ER-status. We evaluated the ability of several next generation SERDs for their brain penetrance and demonstrated that SERD presence in the brain was associated with a stimulatory effect on tumor growth. Interestingly, administration of a low dose of 17b-estradiol (E2) together with a brain excluded SERD further repressed tumor growth, highlighting a potentially beneficial anti-tumor role for estrogen signaling in the brain. Furthermore, combination of a brain excluded SERM with E2 also resulted in increased tumor growth repression; thus, ER downregulation is dispensable for the cooperative activity observed for estrogens administered together with a peripheral ER antagonist. These data suggest that differences in tissue pharmacology, as opposed to differences in ability to degrade ER, is likely to be a major differentiator of ER modulators. Presentation: 6/3/2024

7441 KNDy Neurons and the Control of the Gonadotropic Axis in Midgestation Fetal Sheep

Abstract Disclosure: R. Amodei: None. S.S. Jonker: None. K. Gribbin: None. E. Lazen: None. C.T. Estill: None. C.E. Roselli: None. Recent evidence suggests that the neuropeptide kisspeptin (Kiss) plays a role to activate and regulate the male reproductive axis to secrete LH and testosterone during a time in gestation critical for brain sexual differentiation. KNDy neurons, an acronym for Kiss neurons that co-express neurokinin B (NKB) and dynorphin (Dyn), regulate pulsatile GnRH/LH secretion and are present in the hypothalamic arcuate nucleus of midgestation sheep fetuses. Notably, KNDy neurons are more abundant in female than in male fetuses. We hypothesize that KNDy-GnRH signaling is established during midgestation and that negative feedback mediated through KNDy neurons serves to regulate levels of testosterone needed for brain masculinization. In the current study, we used immunofluorescence histochemistry to assess the effect of testosterone manipulations on the number of arcuate Kiss neurons in male and female fetuses. In addition, we employed unanesthetized cannulated midgestation fetal sheep to test the effects of KNDy peptides on LH secretion and characterize receptor specificity in a real-time physiological context. We found that biweekly administration of testosterone propionate to the dam from Day 30–58 of gestation significantly increased (P < 0.05) plasma testosterone concentrations, which resulted in a significant decrease (P < 0.05) in both mean plasma LH concentrations and the number of arcuate Kiss neurons in female lamb fetuses. Conversely, chemical castration of midgestation male fetuses by treatment with the GnRH antagonist degarelix from day 60 – 90 of gestation resulted in a significant decrease (P < 0.05) in mean plasma LH and testosterone concentrations that was accompanied by a significant increase (P < 0.05) in the number of arcuate Kiss neurons. In unanesthetized fetuses, we found that bolus administration of both KP-10 (Kiss agonist) and senktide (NKB agonist) elicited a robust release of LH within 15 min. Treatment with the NK3 receptor antagonist SB222200 effectively blocked the senktide response, whereas the Kiss1 receptor antagonist P271 appeared to have an effect in males only. Blocking κ-opiate receptor (KOR) with a bolus injection of the KOR antagonist PF4455242 resulted in a significant increase in LH release and enhanced the stimulatory effect of senktide. These results support the hypothesis that KNDy neurons play a regulatory role in GnRH and hence gonadotropin secretion in sheep fetuses and serve as targets for negative feedback in males for maintaining a stable androgen environment crucial for brain masculinization. Supported by NIH Grant OD11047 to CER. Presentation: 6/1/2024

Moderating effect of business environment on the relationship between fiscal science and technology expenditure and venture capital

This study examines the nexus between fiscal science and technology (S&T) expenditure and venture capital growth using panel data from 293 prefecture-level cities from 2005 to 2022. Findings reveal that fiscal investments in S&T promote the development of venture capital. Furthermore, favorable business and financial environments positively moderate the stimulatory effect of fiscal S&T expenditure on venture capital. The impact of fiscal S&T expenditure on venture capital varies by region. This study bridges the theoretical gap in understanding the implications of the government's indirect support policies for venture capital and offers a fresh perspective on the dynamics between government and market forces.

Design, synthesis and biological evaluation of arylpropylamine derivatives as potential multi-target antidepressants

In this study, a series of novel arylpropylamine derivatives were designed, synthesized and evaluated as potential multi-target antidepressants. Among them, compound (R)-13j displayed unique pharmacological features, exhibiting excellent inhibitory potency against serotonin and noradrenaline transporters (SERT/NET) and high affinity for 5-HT2A/2C receptor, and showing low affinity for histamine H1, adrenergic α1 receptors and hERG channels (to reduce QT interval prolongation). Molecular docking studies provided a rational binding model of (R)-13j in complex with SERT and 5-HT2A/2C receptor. In animal models, compound (R)-13j dose-dependently reduced the immobility time in the tail suspension test (TST) and the forced swimming test (FST) in mice, with higher efficacy when compared to duloxetine, and showed no stimulatory effect on the locomotor activity. Moreover, compound (R)-13j significantly shortened the immobility time in the ACTH-induced rat model of treatment-resistant depression (TRD). Furthermore, compound (R)-13j also exhibited a higher threshold for acute toxicity than duloxetine. In addition, compound (R)-13j possessed a favorable pharmacokinetic profile in mice. Taken together, compound (R)-13j may constitute a novel class of drugs for the treatment of depression.

Within-episode relations among simultaneous alcohol and cannabis use and continued drinking: The role of momentary subjective responses, craving, and drinking context.

Simultaneous alcohol and cannabis use is associated with riskier daily drinking. However, little research has tested momentary mechanisms through which simultaneous use predicts continued drinking during acute drinking episodes. The current study tested whether simultaneous use moments predicted within-episode increases in subjective responses, craving, and continued drinking, and whether these relations were potentiated in social versus solitary settings. Emerging adults who co-use alcohol and cannabis (N = 85) completed 21 days of ecological momentary assessment with event-contingent reports during drinking episodes. Three-level multilevel models tested whether simultaneous (vs. alcohol-only) use moments indirectly predicted subsequent, continued drinking through subjective responses (i.e., high-arousal positive/stimulant, high-arousal negative/aggression, low-arousal positive/relaxation, low-arousal negative/impairment) and alcohol craving, and whether relations differed by social versus solitary contexts. Within drinking episodes, simultaneous (vs. alcohol-only) use moments were associated with increased stimulation, which was indirectly associated with continued drinking through increased alcohol craving. Additionally, the relation between simultaneous (vs. alcohol-only) use and stimulating effects was potentiated during solitary drinking moments, whereas the relation between stimulating effects and craving was potentiated during social drinking moments. However, stimulating effects were higher in social contexts across all moments. Finally, simultaneous (vs. alcohol-only) use moments were associated with increased relaxation, which was indirectly associated with a lower likelihood of continued drinking through lesser craving. Simultaneous use predicted both continued within-episode drinking and cessation of drinking, with acute subjective effects and craving as mechanisms, dependent upon context. Just-in-time interventions should consider targeting affect, craving, and context in event-specific interventions.

Regulation of voltage-gated sodium channels by TNF-α during herpes simplex virus latency establishment.

During lytic or latent infection of sensory neurons with herpes simplex virus type 1 (HSV-1) there are significant changes in the expression of voltage-gated Na+ channels, which may disrupt the transmission of pain information. HSV-1 infection can also evoke the secretion of various pro-inflammatory cytokines, including TNF-α and IL-6. In this work, we hypothesized that TNF-α regulates the expression of Na+ channels during HSV-1 latency establishment in ND7/23 sensory-like neurons. Latency establishment was mimicked by culturing HSV-1 infected ND7/23 cells in the presence of acyclovir (ACV) for 3 days. Changes in the functional expression of voltage-gated Na+ channels were assessed by whole-cell recordings. Our results demonstrate that infection of ND7/23 cells with the HSV-1 strain McKrae with GFP expression (M-GFP) causes a significant decrease in sodium currents during latency establishment. Exposure of ND7/23 cells to TNF-α during latency establishment reverses the effect of HSV-1, resulting in a significant increase in sodium current density. However, Na+ currents were not restored by 3day-treatment with IL-6. There were no changes in the pharmacological and biophysical properties of sodium currents promoted by TNF-α, including sensitivity to tetrodotoxin and the current-voltage relationship. TNF-α stimulation of ND7/23 cells increases p38 signaling. Inhibition of p38 signaling with SB203580 or SB202190 eliminates the stimulatory effect of TNF-α on sodium currents. These results indicate that TNF-α signaling in sensory neurons during latency establishment upregulates the expression of voltage-gated Na+ channels in order to maintain the transmission of pain information.

Mechanism and spatial spillover effect of digital economy on common prosperity in the Yellow River Basin of China

The digital economy has emerged as a new trend in economic development and has profoundly influenced the process of achieving common prosperity. However, current research on the correlation between the digital economy and common prosperity from the perspective of a river basin still needs to be strengthened. Based on this, the present study first theoretically elaborates the conceptual meanings of “digital economy” and “common prosperity”, as well as the mechanism by which the digital economy empowers common prosperity. Subsequently, a scientifically-constructed performance evaluation index system for the digital economy and common prosperity is established. Considering the Yellow River Basin as an empirical case study area, this study investigates the mechanism and spatial spillover effects of the digital economy in empowering common prosperity from 2005 to 2020. The research findings reveal that: (1) The Yellow River Basin exhibits a basin characteristic with downstream > midstream > upstream areas regarding the level of common prosperity and digital economy. It indicates that a distinct spatial correlation exists between the two factors. However, the ongoing decrease in both high-level and very high-level areas reflects the lengthy and challenging journey of enhancing the quality and efficiency of the digital economy in empowering common prosperity. (2) The digital economy not only directly impacts common prosperity, but also fosters its development through spatial spillover effects. Among the control factors, informatization and housing levels have a major stimulating effect. (3) There exists a clear regional heterogeneity in how the digital economy affects common prosperity in the Yellow River Basin. Specifically, common prosperity of downstream cities is significantly impacted by the digital economy. The spatial spillover effects of the digital economy on common prosperity exhibit a pronounced “neighborhood as a moat” characteristic. (4) The digital economy facilitates the achievement of shared prosperity through the implementation of mechanisms centered on sharing, affluence, and sustainability. These research findings illuminate the empowering mechanisms and spatial spillover pathways of the digital economy in promoting shared prosperity, aligning with national strategies for ecological conservation and high-quality development in the Yellow River Basin.

Modulation of UPF1 catalytic activity upon interaction of SARS-CoV-2 Nucleocapsid protein with factors involved in nonsense mediated-mRNA decay.

The RNA genome of the SARS-CoV-2 virus encodes for four structural proteins, 16 non-structural proteins and nine putative accessory factors. A high throughput analysis of interactions between human and SARS-CoV-2 proteins identified multiple interactions of the structural Nucleocapsid (N) protein with RNA processing factors. The N-protein, which is responsible for packaging of the viral genomic RNA was found to interact with two RNA helicases, UPF1 and MOV10 that are involved in nonsense-mediated mRNA decay (NMD). Using a combination of biochemical and biophysical methods, we investigated the interaction of the SARS-CoV-2 N-protein with NMD factors at a molecular level. Our studies led us to identify the core NMD factor, UPF2, as an interactor of N. The viral N-protein engages UPF2 in multipartite interactions and can negate the stimulatory effect of UPF2 on UPF1 catalytic activity. N also inhibits UPF1 ATPase and unwinding activities by competing in binding to the RNA substrate. We further investigate the functional implications of inhibition of UPF1 catalytic activity by N in mammalian cells. The interplay of SARS-CoV-2 N with human UPF1 and UPF2 does not affect decay of host cell NMD targets but might play a role in stabilizing the viral RNA genome.

Dose-dependent effect of cadaverine on hydroxyl radicals’ production by human peripheral blood leukocytes

Objective. To assess changes in the generation of hydroxyl radicals by leukocytes under the influence of cadaverine at concentrations of 1, 5 and 25 mmol/L. Materials and methods. Peripheral venous blood samples were obtained from 40 apparently healthy donors. To assess the production of hydroxyl radicals, a luminol-dependent chemiluminescence reaction with blood leukocytes, which were pre-incubated with cadaverine at concentrations of 1, 5 and 25 mmol/L was carried out. The study was conducted on a Luminoskan Ascent® Thermo Labsystems (USA) luminometer for 180 minutes. For statistical analysis, the integral chemiluminescence indicator for the entire measurement period (RLU) was used. The time to reach the maximum of light flashes in minutes, the intensity of the utmost glow, and the area under the luminescence extinction curve were calculated. Results. It was determined that pre-incubation of cells with cadaverine significantly reduces their time to reach the maximum generation of hydroxyl radicals. In addition, cadaverine enhances the intensity of the reaction of luminol-dependent chemiluminescence of leukocytes of healthy donors, and the greatest stimulating effect was recorded at a polyamine concentration of 5 mmol/L (p =0,009 to samples with a spontaneous reaction, p =0,007 and 0,010 to samples with cadaverine 1 mmol/L and 5 mmol/L respectively). Cadaverine increases the area under the reaction curve, it being the most significant at a concentration of 5 mmol/L – 20.89±3.00 c.u. versus 0.86±0.07 c.u. with a spontaneous reaction (p=0,001). Conclusions. The results of the study indicate a possible effect of cadaverine on the mechanisms of hydroxyl radical formation, as well as the activity of the diamine oxidase enzyme in leukocytes. It can be supposed that the combination of these effects contributes to the development of the environment favorable for microorganisms at the focus of inflammation. Thus, microorganisms that produce cadaverine, which modulates the generation of hydroxyl radicals by leukocytes, adapt to their environment, creating a special type of microenvironment, which probably results in an asymptomatic course of the inflammatory process.

Efficacy of Bacillus spp. Isolates for Application as Biofertilizer in Tomato (Solanum lycospersicum L.) Cultivation

Certain species of Bacillus are considered rhizobacteria that promote plant growth, inhibit the growth of plant pathogens and deleterious rhizospheric microorganisms. The aim of this study was to determine the stimulatory effect of Bacillus subtilis KBM1 and Bacillus venezensis KBM1 on the growth and disease reduction of tomato plants in Côte d'Ivoire. In this respect, three substrates consisting of soil only, sawdust only and a mixture of soil and sawdust were inoculated with the two bacteria, then left to ferment for twenty-four (24) hours. The biofertilizers obtained after fermentation were used to assess their effects on the development of potted tomatoes. Growth parameters, infection rate and mortality rate of tomato plants were measured regularly during 6 weeks of cultivation. A search for tomato pathogenic fungi was carried out to demonstrate the efficacy of Bacillus strains isolates on plant health. The results obtained showed that Bacillus subtilis KBM1 and Bacillus venezensis KBM1 had a positive impact on plant growth of tomato plants grown. Infection and mortality rates of 0% were observed for tomato plants grown on the three substrates inoculated with these two bacteria. No pathogenic fungi were isolated from the organs of tomato plants grown on the three substrates fermented with the bacteria. However, on untreated control plants, a variety of pathogenic fungi, namely Fusarium sp, Phytophtora sp, Cladosporium sp, Rhizoctonia sp, Colletotrichum sp, Penicillium sp, Rhizopus sp and Trichoderma sp were observed. However, the Bacillus subtilis KBM1 treatment stood out from Bacillus venezensis KBM1 with the best results for the growth parameters measured. In view of these results, these two bacteria could be used to produce an effective biofertilizer for tomato cultivation in Côte d'Ivoire.

How does data factor utilization stimulate corporate total factor productivity: A discussion of the productivity paradox

Stimulating total factor productivity through the utilization of data factors is a crucial concern for companies operating in the digital era. This study employs data from A-share listed firms from 2011 to 2022 to examine the impact and mechanisms of data utilization on corporate total factor productivity. The findings reveal that effective data utilization can significantly improve corporate total factor productivity, but no evidence supports the productivity dilemma. The stimulating effects are achieved by alleviating investment inefficiency and resource redundancy. Further analysis verifies that firms` financial performance and life cycle can lead to heterogeneous effects. Specifically, the positive impact is more pronounced in firms with lower operational performance and in periods of maturity and recession.

The neural regulation and impact of posterior nasal neurectomy on nasal ciliary motion in vivo in a murine allergic rhinitis model.

Posterior nasal neurectomy (PNN) is a commonly employed surgical approach for the treatment of allergic rhinitis (AR). Due to its denervation effect on the nasal mucosa, PNN may potentially alter the motion and defensive capability of cilia. Previous research on the effects of neural regulation and denervation on cilia has been limited by the absence of a feasible in vivo evaluation method for assessing ciliary function. Utilizing a new system developed by our team for visualizing and analyzing ciliary motion in vivo, we analysed ciliary beat frequency and distance in vivo and histomorphological changes in a murine PNN and AR model. Ovalbumin, histamine and neurotransmitters (acetylcholine chloride, α receptor agonist and β receptor agonist) were applied to investigate the responsiveness and neural regulation of the nasal mucosa. Denervation resulting from PNN led to a reduction in nasal ciliary beat frequency (CBF) to 78% of the control, as well as diminished response towards allergens and histamine. Among neurotransmitters examined, α receptor agonists exhibited inhibitory effects on in vivo ciliary motion while acetylcholine and β receptor agonists demonstrated stimulatory effects. PNN did not affect the reactivity of in vivo cilia towards these neurotransmitters. PNN-induced denervation can reduce ciliary motion, potentially compromising the defensive capability of nasal mucosa. Neural regulation and the neurotransmitters involved have significant effect on ciliary motion.

Electric fields to support microalgae growth with a differentiated biochemical composition

Microalgae are a group of microorganisms well-known for their high metabolic plasticity and biomass with commercial interest for several industries. In the present work, the influence of in-situ electric field application (INEF) on the growth and biochemical composition of Pavlova gyrans was, for the first time, assessed. Electrical protocols were tested, namely by applying INEF in different growth stages, in varying treatment times and even by combining it with dark phase of cells' photoperiod. INEF did not promote a stimulatory effect on growth but influenced the biochemical composition of P. gyrans – maximum increases of 74.9 and 66.2 % in the chlorophyll a and carotenoid content and of 4.72, 18.7 and 5.41 % in the lipid, carbohydrate and protein content were observed in independent experiments. Hence, with this study, the potential of INEF application as a strategy to modulate growth and to promote biochemical composition alterations was proven. Industrial relevanceMicroalgae, with their unique ability to efficiently convert sunlight and carbon dioxide into biomass, offer a sustainable platform for the synthesis of diverse bioactive compounds. By subjecting microalgae to controlled electric stress conditions, their metabolic pathways can be redirected towards the production of specific target compounds. This strategy has the potential to enhance the yield of high-value molecules, including biofuels, pharmaceuticals, nutraceuticals, and pigments, whilst minimizing resource inputs. Additionally, metabolic stress responses in microalgae often trigger the accumulation of secondary metabolites with bioactive properties. Harnessing the metabolic plasticity of microalgae through controlled stress manipulation represents a cutting-edge strategy for sustainable and economically viable bioproduction systems that align with the goals of green chemistry and circular economy principles.

Insights into the carbon and nitrogen metabolism pathways in mixed-autotrophy/heterotrophy anammox consortia in response to temperature reduction

While the multi-coupled anammox system boasts a substantial research foundation, the specific characteristics of its synergistic metabolic response to decreased temperatures, particularly within the range of 13-15°C, remained elusive. In this study, we delve into the intricate carbon and nitrogen metabolism pathways of mixed-autotrophy/heterotrophy anammox consortia under conditions of temperature reduction. Our macrogenomic analyses reveal a compelling phenomenon: the stimulation of functional genes responsible for complete denitrification, suggesting an enhancement of this process during temperature reduction. This adaptation likely contributes to maintaining system performance amidst environmental challenges. Further metabolic functional recombination analyses highlight a dramatic shift in microbial community composition, with denitrifying MAGs (metagenome-assembled genomes) experiencing a substantial increase in abundance (up to 200 times) compared to autotrophic MAGs. This proliferation underscores the strong stimulatory effect of temperature reduction on denitrifying species. Notably, autotrophic MAGs play a pivotal role in supporting the glycolytic processes of denitrifying MAGs, underscoring the intricate interdependencies within the consortia. Moreover, metabolic variations in amino acid composition among core MAGs emerge as a crucial adaptation mechanism. These differences facilitate the preservation of enzyme activity and enhance the consortia's resilience to low temperatures. Together, these findings offer a comprehensive understanding of the microbial synergistic metabolism within mixed-autotrophy/heterotrophy anammox consortia under temperature reduction, shedding light on their metabolic flexibility and resilience in dynamic environments.

Effects of polystyrene nano- and microplastics on human breast epithelial cells and human breast cancer cells

The continuous littering of the environment with plastic and the resulting nano- and microplastics produced from various processes are ever-increasing problems. These materials also affect humans, as the absorption and accumulation of nano- and microplastics and their effects on health have thus far been rarely researched, which also applies to cancer. In the present study, the absorption of different sizes of polystyrene (PS) nano- and microplastics (PS particles) into human breast epithelial cells and human breast cancer cells was investigated. Subsequently, how the proliferation, colony and mammosphere formation abilities, cell fusion and migration of the cells were influenced by the PS particles were investigated. Our data revealed granularity-, dose- and cell line-dependent absorption of the PS particles, with the highest absorption observed in the MDA-MB-231-DSP1-7 cells and the lowest in the M13SV1_Syn1-DSP8-11 cells. Neither the colony-forming ability nor the cell fusion activity increased with the addition of PS particles. In contrast, slight, partially significant stimulatory effects on both proliferation and cell migration were observed, although these effects depended on the particle quantity and size and the cell line used. In summary, PS particles are absorbed by human breast epithelial and human breast cancer cells and influence cells that may be associated with cancer progression.