Consecutive Applications Research Articles

TRPV1 corneal neuralgia mutation: Enhanced pH response, bradykinin sensitization, and capsaicin desensitization

The factors that contribute to pain after nerve injury remain incompletely understood. Laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) are common surgical techniques to correct refractive errors. After LASIK or PRK, a subset of patients suffers intense and persistent pain, of unknown origin, described by patients as feeling like shards of glass in their eye. Here, we evaluated a TRPV1 variant, p.V527M, found in a 49-y-old woman who developed corneal pain after LASIK and subsequent PRK enhancement, reporting an Ocular Surface Disease Index score of 100. Using patch-clamp and Ca2+ imaging, we found that the V527M mutation enhances the response to acidic pH. Increasing proton concentration induced a stronger leftward shift in the activation curve of V527M compared to WT, resulting in channel activity of the mutant in acidic pH at more physiological membrane potentials. Finally, comparing the responses to consecutive applications of different agonists, we found in V527M channels a reduced capsaicin-induced desensitization and increased sensitization by the arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE). We hypothesize that the increased response in V527M channels to protons and enhanced sensitization by 12-HETE, two inflammatory mediators released in the cornea after tissue damage, may contribute to the pathogenesis of corneal neuralgia after refractive surgery.

Nanotechnology in Agriculture: Manganese Ferrite Nanoparticles as a Micronutrient Fertilizer for Wheat.

Limited research has focused on nanoparticle (NP) applications' impact on edible wheat parts in a field environment. Here, we studied the nutritional quality of edible parts of wheat (Triticum aestivum L.) with a field experiment by spraying MnFe2O4 nanoparticles. Wheat was foliar sprayed with 0, 25, 50, and 100 mg/L composite manganese ferrite (MnFe2O4) NPs during 220 d of a growth period. Ionic controls were prepared using the conventional counterparts (MnSO4·H2O and FeSO4·7H2O) to compare with the 100 mg/L MnFe2O4 NPs. After three consecutive foliar applications, nanoparticles demonstrated a substantial elevation in grain yield and harvest index, exhibiting a noteworthy increase to 5.0 ± 0.12 t/ha and 0.46 ± 0.001 in the 100 mg/L NP dose, respectively, concomitant with a 14% enhancement in the grain number per spike. Fe, Mn, and Ca content in grain increased to 77 ± 2.7 mg/kg, 119 ± 2.8 mg/kg, and 0.32 ± 7.9 g/kg in the 100 mg/L NPs, respectively. Compared to the ion treatment, the 100 mg/L NP treatments notably boosts wheat grain crude protein content (from 13 ± 0.79% to 15 ± 0.58%) and effectively lowers PA/Fe levels (from 11 ± 0.7 to 9.3 ± 0.5), thereby improving Fe bioavailability. The VSM results exhibited a slight superparamagnetic behavior, whereas the grains and stems exhibited diamagnetic behavior. The results indicate that the nanomaterial did not accumulate in the grains, suggesting its suitability as an Fe and Mn-rich fertilizer in agriculture. Above all, the foliar application of nanocomposites increased the concentrations of Fe, Mn, and Ca in wheat grains, accompanied by a significant enhancement in grain yield. Therefore, the research results indicate that the foliar application of MnFe2O4 NPs can positively regulate wheat grains' nutritional quality and yield.

Exploring factors that influence the efficacy of functional communication training.

Understanding factors that influence the efficacy of functional communication training has both practical and conceptual benefits. The current study extended research in this area by exploring data from 95 consecutive applications of functional communication training with extinction across two independent clinics. We selected candidate predictor variables based on conceptual analysis, conducted preliminary exploratory analyses, and then selectively applied quantitative methods that are used in precision medicine to examine their accuracy and predictive utility. Treatment outcomes were better when challenging behavior was maintained by a single function than they were when it was maintained by multiple functions; however, these differences were most apparent among cases with an escape function. We also analyzed within-session responding to explore the potential influence of unprogrammed establishing operations on decrements in treatment efficacy. Our within-session measure only distinguished responders from nonresponders when escape was one of the multiple functions. Additional research is needed to validate these findings with an independent sample and to address a number of clinical conceptual issues.

Effects of foliar iron oxide nanoparticles (Fe3O4) application on photosynthetic parameters, distribution of mineral elements, magnetic behaviour, and photosynthetic genes in tomato (Solanum lycopersicum var. cerasiforme) plants

This study aims to examine the effect of foliar magnetic iron oxide (Fe3O4) nanoparticles (IONP) application on the physiology, photosynthetic parameters, magnetic character, and mineral element distribution of cherry tomatoes (Solanum lycopersicum var. cerasiforme). The IONP suspension (500 mg L−1) was sprayed once (S1), twice (S2), thrice (S3), and four times (S4) a week on seedlings. Upon 21 days of the treatments, photosynthetic parameters (chlorophyll, carotenoids, photosynthetic yield, electron transport rate) were elucidated. Inductively-coupled plasma-optical emission spectrometer (ICP-OES) and vibrating sample magnetometer (VSM) were used to determine the mineral elements and abundance of magnetic power in the seedlings. In addition, the RT-qPCR method was performed to quantify the expressions of photosystem-related (PsaC, PsbP6, and PsbQ) and ferritin-coding (Fer-1 and Fer-2) genes. Results revealed that the physiological and photosynthetic indices were improved upon S1 treatment. The optimal dosage of IONP spraying enhances chlorophyll, carotenoid, electron transport rate (ETR), and effective photochemical quantum yield of photosystem II (Y(II)) but substantially diminishes non-photochemical quenching (NPQ). However, frequent IONP applications (S2, S3, and S4) caused growth retardation and suppressed the photosynthetic parameters, suggesting a toxic effect of IONP in recurrent treatments. Fer-1 and Fer-2 expressions were strikingly increased by IONP applications, suggesting an attempt to neutralize the excess amount of Fe ions by ferritin. Nevertheless, frequent IONP treatment fluctuated the mineral distribution and caused growth inhibition. Although low-repeat foliar applications of IONP (S1 in this study) may help improve plant growth, consecutive applications (S2, S3, and S4) should be avoided.

Effect of strontium fluorophosphate bioactive glass on color, microhardness and surface roughness of bleached enamel.

Undesirable effects of tooth bleaching can alter the biomechanical properties of enamel. To determine the influence of strontium fluorophosphate bioactive glass (Sr-FPG) on color, microhardness and surface roughness of enamel bleached with 35% hydrogen peroxide. The labial enamel of 36 extracted intact human anterior teeth were divided into 3 groups (n= 12), group 1 (HP): bleaching with 35% hydrogen peroxide only, group 2 (Sr-HP): bleaching with Sr-FPG incorporated 35% hydrogen peroxide and group 3 (HP-SrFPG): bleaching with 35% hydrogen peroxide followed by remineralization with Sr-FPG. Four consecutive eight-minute applications of the bleaching gel were done twice in all the groups. Color change (ΔE), microhardness and surface roughness were evaluated at baseline, post-bleaching and post-remineralization using spectrophotometer, Vickers hardness tester and profilometric analysis respectively. The mean ΔE among the groups was statistically similar (p> 0.05). Bleaching with HP significantly reduced microhardness (p< 0.05), whereas bleaching with Sr-HP and HP-SrFPG did not (p> 0.05). Post-bleaching microhardness in Sr-HP was significantly higher than HP-SrFPG (p< 0.05). An increased surface roughness was seen in Sr-HP bleached samples (p< 0.05). The addition of Sr-FPG to hydrogen peroxide significantly improved enamel microhardness than its use post-bleaching. An increase in surface roughness was seen post-bleaching with HP and Sr-HP.

Fletcher suit or ring: A comparison of Fletcher suit and ring applicators for retroverted uteri.

Approximately 20% of women worldwide have a retroverted uterus. A retroverted uterus is closer to the rectum and may cause toxicity during brachytherapy. Upon manipulation, a small percentage turn anteverted. Conventional brachytherapy applicators are designed for an anteverted uterus and can pose issues during insertion. Modified Fletcher suit and ring applicators have major differences in their geometry to achieve similar target coverage, and were analyzed in this study with respect to immediate adverse events and dosimetry. Three hundred seventy-four consecutive applications performed over a 20-month period were studied retrospectively to identify intra-cavitary applications (ICAs) in retroverted uteri. Cases were divided into 2 groups: modified Fletcher suit applicator with hemi-ovoids (group A) and ring applicator (group B). D2cc for bladder and rectum were noted, and acute adverse events were recorded. Seventy-five applications were identified, out of which 47 cases used Fletcher suit applicator, and 28 cases used ring applicator. The median bladder D2cc for group A and B were 5.98 Gy and 6.3 Gy, respectively, and the median rectum D2cc was 5.27 Gy and 3.68 Gy, respectively; the median dose prescribed to point A was 6 Gy (range, 5.5-9.0 Gy). All patients had a point A coverage between 97% and 102%. Eighteen cases in both groups complained of pain requiring analgesics. Twenty-five cases (53.2%) and 20 cases (71.4%) in group A and B, respectively, required dose optimization, which was statistically insignificant (p > 0.11). A significant difference was identified (p < 0.00001) in rectal doses. A higher reported pain was noted in ring applicator group (p < 0.03). No patient experienced a profuse bleeding. In most parameters, the two applicators demonstrated comparable results. The control of rectal dosage is superior in the ring applicator at the cost of higher pain incidence. Patient's comfort and rectal dose in EBRT should be taken into consideration, with preference given to the ring applicator.

Consecutive Transcutaneous and Epidural Spinal Cord Neuromodulation to Modify Clinical Complete Paralysis—the Proof of Concept

ObjectiveTo evaluate the effect of transcutaneous (tSCS) and epidural electrical spinal cord stimulation (EES) in facilitating volitional movements, balance, and nonmotor functions, in this observational study, tSCS and EES were consecutively tested in 2 participants with motor complete spinal cord injury (SCI). Participants and MethodsTwo participants (a 48-year-old woman and a 28-year-old man), both classified as motor complete spinal injury, were enrolled in the study. Both participants went through a unified protocol, such as an initial electrophysiological assessment of neural connectivity, consecutive tSCS and EES combined with 8 wks of motor training with electromyography (EMG) and kinematic evaluation. The study was conducted from May 1, 2019, to December 31, 2021. ResultsIn both participants, tSCS reported a minimal improvement in voluntary movements still essential to start tSCS-enabled rehabilitation. Compared with tSCS, following EES showed immediate improvement in voluntary movements, whereas tSCS was more effective in improving balance and posture. Continuous improvement in nonmotor functions was found during tSCS-enabled and then during EES-enabled motor training. ConclusionResults report a significant difference in the effect of tSCS and EES on the recovery of neurologic functions and support consecutive tSCS and EES applications as a potential therapy for SCI. The proposed approach may help in selecting patients with SCI responsive to neuromodulation. It would also help initiate neuromodulation and rehabilitation therapy early, particularly for motor complete SCI with minimal effect from conventional rehabilitation.

Effects of mixtures of herbicides on nutrient cycling and plant support considering current agriculture practices

The use of mixtures of pesticides and consecutive pesticide applications challenge current regulations aimed at protecting ecosystem health due to unpredictable effects of complex and dynamic mixtures. In this study, we tested the ecotoxicological effects of mixtures of herbicides, applied following a real application scheme of soybean production on soil health in a mesocosm experiment. The experiment included two sequential applications; first, glyphosate + dicamba + clethodim, and 30 days later, flumioxazin + metolachlor. Commercial products were used at the recommended doses and at two other concentrations: half and double the recommended dose. Soybean plants were exposed to the herbicide-contaminated soil from the time of sowing to the beginning of pod formation. Half of the plants were harvested at the vegetative stage and the remaining plants at the reproductive stage to evaluate endpoints related to plant support and nutrient cycling. Plant biomass was significantly affected during the vegetative stage at the recommended and double the recommended dose, with the effects being mixture-dose dependent. Lower total and arbuscular colonization of mycorrhizas were also observed in double the recommended dose, and intermediate results were observed for the recommended dose. Nodule mass and phosphorous concentration in plants decreased with increasing herbicide doses. By the end of the experiment, nodule mass and total mycorrhizal colonization were low in the plants treated with double the recommended dose of herbicides. However, both endpoints reached similar values to the control at lower herbicide doses. Plant height and phenology were only lower at double the recommended dose during the experiment. The use of non-standard endpoints evidenced that important soil functions were transiently or permanently affected, while the realistic application scheme accounted for the impact of the management practice currently used. Pesticide risk assessment should therefore, incorporate both issues to effectively protect the ecosystems.

Effects of Photobiomodulation Therapy on Hard Tissue Healing in Rat Tooth Extraction Sockets.

Objective: To investigate the effects of photobiomodulation therapy (PBMT) on hard tissue healing in rat maxillary first molar extraction sockets. Methods: A total of 20 male Wistar rats were used in the study. The right extraction sockets were irradiated with a Ga-Al-As laser (500 mW, 980 nm) for 51.7 J/cm2 every 24 h for 7 days, while the left sockets served as controls. Rats were sacrificed on days 3, 7, 14, and 28 after tooth extraction, and microcomputed tomography (CT) analysis, histopathological evaluation, and enzyme-linked immunosorbent assay (ELISA) were conducted at different time points. Results: Micro-CT analysis showed that the percentage of bone volume/tissue volume (TV) and bone mineral density were significantly higher in the experimental group compared to the control group on day 28 (p < 0.05). Histopathological evaluation revealed that PBMT promoted new bone formation and accelerated bone remodeling. ELISA demonstrated a significant increase in alkaline phosphatase expression in the laser sides on days 7 and 14 (p < 0.05). Conclusions: One application postextraction followed by seven consecutive daily applications of PBMT can effectively promote hard tissue healing in rat maxillary first molar extraction sockets.

Determination of Tiamulin Concentration in Sow Milk and in Sera of Suckling Piglets.

Although modern analytical methods developed for monitoring antibiotics in several biological matrices are easily available, none of them have been applied to evaluate the transfer of tiamulin into sow milk. Therefore, this work was intended to analyse the concentrations of tiamulin in milk samples collected from lactating sows during and after a treatment consisting of three consecutive intramuscular applications of the antibiotic. The second aim of this investigation was to determine tiamulin concentrations in serum samples obtained from suckling piglets ingesting milk contaminated with the compound. Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) was used to quantify the analyte in both matrices. Our investigation proved tiamulin was transmitted into the milk of lactating sows. The mean concentration of the antibiotic among samples collected 3 h after administration was 1043 μg/L. The mean level of tiamulin on days 1 and 2 was 876 μg/L and 902 μg/L, respectively. The highest mean concentration of the antibiotic (1061 μg/L) was observed in samples collected on day 3. The mean concentration of the antibiotic in serum samples collected from 3-day-old piglets was 22.2 μg/L. The association between their body weight and serum tiamulin concentration was not statistically significant (p = 0.456).

First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study

BackgroundFollowing resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control.MethodsThree glioblastoma patients underwent tumor resection followed by standard radio- and chemotherapy. These patients with stable disease following completion of standard therapy underwent iRIT on compassionate grounds. After surgical implantation of a subcutaneous injection reservoir with a catheter into the resection cavity, a leakage test with [99mTc]Tc-DTPA was performed to rule out leakage into other cerebral compartments. IRIT comprised three consecutive applications over three months for each patient, with 25%, 50%, 25% of the total activity injected. A dosimetry protocol was included with blood sampling and SPECT/CT of the abdomen to calculate doses for the bone marrow and kidneys as potential organs at risk.ResultsAll three patients presented without relevant leakage after application of [99mTc]Tc-DTPA. Two patients underwent three full cycles of iRIT (592 MBq and 1228 MBq total activity). One patient showed histologically proven tumor progression after the second cycle (526 MBq total activity). No relevant therapy-associated toxicities or adverse events were observed. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk.ConclusionsIn first individual cases, iRIT with [177Lu]Lu-6A10-Fab appears to be feasible and safe, without therapy-related side effects. A confirmatory multicenter phase-I-trial was recently opened and is currently recruiting.

Roles and Preliminary Mechanism of Tobacco cis-Abienol in Inducing Tomato Resistance against Bacterial Wilt.

Bacterial wilt negatively impacts the yield and quality of tomatoes. cis-Abienol, a labdane diterpenoid abundantly produced in the trichome secretion of Nicotiana spp., can induce bacterial wilt resistance in plants; however, study on its practical application and acting mechanism is very limited. This study established the application conditions of cis-abienol for inducing tomato bacterial wilt resistance by pot-inoculation experiments and investigated the underlying mechanism by determining the physio-biochemical indexes and transcriptomic changes. The results showed that applying cis-abienol to the roots was the most effective approach for inducing tomato bacterial wilt resistance. The optimal concentration was 60 μg/mL, and 2-3 consecutive applications with 3-6 days intervals were sufficient to induce the bacterial wilt resistance of tomato plants. cis-Abienol could enhance the antioxidant enzyme activity and stimulate the defensive signal transduction in tomato roots, leading to the upregulation of genes involved in the mitogen-activated protein kinase cascade. It also upregulated the expression of JAZ genes and increased the content of jasmonic acid (JA) and salicylic acid (SA), which control the expression of flavonoid biosynthetic genes and the content of phytoalexins in tomato roots. cis-Abienol-induced resistance mainly depends on the JA signalling pathway, and the SA signalling pathway is also involved in this process. This study established the feasibility of applying the plant-derived terpenoid cis-abienol to induce plant bacterial wilt resistance, which is of great value for developing eco-friendly bactericides.

Safety and Pharmacokinetics of PSD502 in Healthy Chinese Male and Female Volunteers: Two Randomized, Double-Blind, Placebo-Controlled, Phase I Trials.

PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals. Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed. Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9% (7/18) of male individuals and 66.7% (12/18) of female individuals in the PSD502 group, respectively. Both trials reported 50.0% (3/6) treatment-emergent adverse events for the placebo. No grade ≥ 3 treatment-emergent adverse events, serious adverse events, or treatment-emergent adverse events leading to early withdrawal or discontinuation occurred. After consecutive applications, lidocaine and prilocaine cleared rapidly in both trials. Plasma concentrations exhibited high inter-individual variability. The maximum plasma concentrations of active ingredients were far below the anticipated minimum toxic concentrations. The area under the plasma concentration-time curve of metabolites were ≤ 20% of the parent drugs. No clinically significant accumulations were observed in the two trials. PSD502 was well tolerated and showed low plasma concentrations in healthy Chinese male and female individuals.

Structuring alginate/dopamine powder into macroscopic aerogel microsphere for exceptional removal of tetracycline from water: Performance and mechanisms

Aerogel was selected as one of IUPAC Top Ten Emerging Technologies in Chemistry in 2022, and has attracted tremendous concerns of scientists in removal of emerging contaminants. In this work a novel Fe3+ cross-linked alginate aerogel (SA/DA-Fe3+) with multiple sorption sites were facilely fabricated and applied for highly efficient removal of tetracycline (TC) from water. Results showed that Fe3+ and DA cooperatively improve adsorption of TC and TC was efficiently removed over a broad pH range of 4–8. The kinetics process can be better described by a chemisorption controlled pseudo-second-order kinetics model and Langmuir isotherm equation with characteristics of monolayer coverage. The fitted qmax value of TC at ambient temperature was 804.6 mg g−1 higher than those of other reported adsorbents. Multiple interactions including π-π EDA, complexation, hydrogen bonding, electrostatic attraction, etc. were involved in adsorption process. Moreover, SA/DA-Fe3+ aerogel exhibited satisfactory stability, reusability, and recyclability for consecutive applications. Most importantly, after consecutively running for >1000 h with dynamic sorption capacity over 500 mg g−1, the packed-column was still not saturated, manifesting its great potentials for treating actual wastewaters. Thus, above superiorities make SA/DA-Fe3+ a promising candidate adsorbent for treating TC-containing wastewater.

Textile composition, not number of layers, impacts interphase pressure and static stiffness index: A pragmatic, comparative analysis of the in vivo interphase pressure of 7 different 2-layer cohesive bandage kits in healthy volunteers

OBJECTIVE: The aim of the study was to comparatively evaluate the in vivo interphase pressure (IP) and statis stiffness index (SSI), upon initial application, of 7, 2-layer cohesive bandage kits when applied on healthy volunteers. METHOD: Bandages were applied in random order, on non-consecutive days by a single experienced clinician. The IP at the time of application was measured on the right lower limb of 10 healthy volunteers at 2 different points (B1, C). Measurements were made in 2 positions, supine and standing. There were 2 consecutive applications and measurements made for each compression bandage set. Statistical analysis of the outcome data was performed, utilizing a repeated measures analysis of variance (ANOVA) to determine: the effects of the bandage type on IP and SSI for each of the measurement points and according to the subject’s position. Post hoc analyses were performed by Tukey and Bonferroni test to identify significant differences. The dispersion of the recorded pressures within the study population (dispersion between subjects) was assessed by the coefficient of variations. RESULTS: The in vivo IP measured at B1 in the supine position varied from 50.1 mmHg (±5.3) to 73.7 mmHg (±13.4). The in vivo IP measured at C in the supine position varied from 53.2 mmHg (±7.6) to 69.3 mmHg (±10.6). Bonferroni post hoc analyses demonstrated with a 95% confidence interval, there was a significant difference between wraps and placed them into 5 groups for the IP measured at B1, and 3 groups for measurements taken at C. A regression model including the main effects of the wrap and the subject with their interaction were similar for the IP observed at B1 and C in the supine position (r2 = 0.881). The in vivo SSI measured at B1 varied from 11.95 (±5.4) to 6.65 (±4.4). Post hoc analyses similarly demonstrated significant differences placing the wraps into 3 different groups. Statistical analysis of the variability of the IP observed at B1 and C showed there was a significant difference at B1 (P = .001), which was not observed at C (P = .347). CONCLUSION: Sub-bandage pressure measurements produced by the 7, ‘2-layer cohesive’ compression box sets were not equivocal. IP and SSI varied by textile composition, clinically supporting the trial of alternative ‘2-layer cohesive’ compression box set if the desired outcome (ie, wound healing, edema reduction) is not achieved. Additional study in patients with edema is warranted to allow an evidenced-based approached to the selection of a compression bandage set.

Nicotine-mediated signaling in glomerular podocytes

Introduction: Although nicotine’s harmful effects on renal function are established, the precise cellular mechanisms of smoking-related damage are understudied. Smoking-Related Glomerulopathy (SRG) is a renal disease phenotype associated with smoking. This condition histologically mimics diabetic nephropathy, however, SRG patients present with proteinuria and renal insufficiency without diabetes. Here we investigated the acute and chronic nicotine-related oxidative and nitrosative stress in glomerular podocytes. We hypothesized that nicotine may promote nitrosative stress in the kidney cells through the rapid production of peroxynitrite (ONOO - ) and a decline in nitric oxide (NO) bioavailability. Methods: To test the hypothesis, we used a conditionally immortalized human podocyte line and confocal imaging to detect the production of ONOO - (Hydroxyl Radical and Peroxynitrite Sensor; HPF), intracellular Ca 2+ (Fluo-8), and NO (DAF-FM). The presence of nicotinic acetylcholine receptors (nAChR) receptor subunits in podocytes was confirmed with immunocytochemistry and live imaging using commercially available pharmacology. NOS activity was analyzed in response to Ang II with the specific blockers for NOS1 (NΩ-Propyl-L-arginine hydrochloride) and NOS2 (L-NIL) subunits. One-way ANOVA (OriginPro) was used for statistical analysis. Results: Immunostaining indicated that human and rat kidneys express nicotinic acetylcholine receptors (nAChR). Notably, we detected specific expression of α7 nAChR in glomerular podocytes. In podocytes, acute nAChR activation promoted the mobilization of intracellular Ca 2+ controlled by intracellular store activation, and fast ONOO - transients. Multiple consecutive applications of nicotine resulted in repeated intracellular Ca 2+ and ONOO - transients. Nicotine-mediated ONOO - response was efficiently blocked in the presence of superoxide dismutase (SOD). The application of specific α7 or α4β2, α2β4, α4β4 and α3β4 nAChR agonists elicited Ca 2+ transients but did not reproduce the ONOO - response to nicotine, suggesting that nitrosative processes may occur independently from Ca 2+ influx or nAChR function. Chronic exposure to nicotine (12-hrs) resulted in a significant decline in podocytes’ NO bioavailability (p&lt;0.05). While under normal conditions, NO is produced primarily by NOS1 (70%), and the rest is attributed to NOS2, chronic nicotine exposure led to an elevation of NOS2 (75%) and a decline in NOS1 activity (p&lt;0.001). We observed similar NOS remodeling under hyperglycemic conditions, suggesting similar nitrosative processes in response to nicotine and high glucose. Conclusions: Nicotine promotes superoxide-stimulated nitrosative stress and peroxynitrite formation in podocytes leading to decline in NO bioavailability and pathological activation of NOS2. R01 NIDDK DK126720 (OP), DK129227 (OP), HL148114 (DVI), NIH/NCATS/SCTR UL1TR001450/SCTR 2214 (OP). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

AGRICULTURE URBAINE: POURVOYEUSE DE DENREES ALIMENTAIRES ET SOURCES DE NUISANCES SANITAIRES AU QUARTIER SODEPRA A KORHOGO (NORD DE LA COTE DIVOIRE)

Urban agriculture is an activity that is developing more and more throughout the city of Korhogo, more specifically in the Logokaha district. Undeveloped areas and low-lying areas in the heart of the neighborhood are being invaded by farmers. The objective of this study is to show the impact of urban agriculture on food production and the health of farmers.To achieve this objective, the methodology was based on documentary research and field survey. The field survey was conducted among 81 farmers using the snowball method.The results show that urban agriculture is generally practiced by women (85.19%) without any level of education (71.61%) who squat the spaces. To improve production, farmers use various types of fertilizers (chemical and biological) and pesticides. The time between two consecutive applications is not respected by the farmers. The packaging of chemical products used is thrown away in the immediate environment by 59.26% of farmers. The products of this agriculture are intended for consumption and sale. Despite its contribution to the empowerment of farmers, it exposes farmers to health problems such as fatigue (53.09%), injuries (25.92%), skin burns (11.11%) and pathologies (dry coughs and colds (32.10% of respondents), and diarrheal diseases (19.75%).In order to increase production and reduce health risks, a resilient, healthy and sustainable production system must be put in place, which requires the involvement of all actors (producers, traders and consumers).

Carboxyl terminus of Pannexin-1 plays a crucial role in P2X7 receptor-mediated signaling

The cellular implications of the interaction between Pannexin-1 (Panx1) channel and P2X7 receptor (P2X7R) have not been fully elucidated. Evidence suggests that ATP, released through Panx1, activates P2X7R, which in turn promotes further activation of Panx1. In a previous study, we reported that the C-terminus of Panx1 (Panx1-CT) attenuates P2X7R-mediated Ca2+ influx and cell death. One of the distinctive features of P2X7R is the gradual increase in current with repetitive stimulation. In the current study, we report an effect of Panx1-CT (amino acid residues 350 to 426) on P2X7R current, which differs from the effect of full-length Panx1. Panx1-CT inhibited P2X7R current, which persisted in all consecutive agonist applications. However, full-length Panx1 reduced P2X7R current at initial stimulations, followed by gradual augmentation. When P2X7R was activated for an extended period, cells expressing Panx1-CT exhibited less mitochondrial depolarization, reactive oxygen species (ROS) generation, Caspase 3 activation and cell death, whereas cells overexpressing full-length Panx1 showed the opposite effect. Taken together, these findings suggest that Panx1 can either attenuate or augment P2X7R-mediated cellular processes depending on the degree of P2X7R activation.

Resistance Risk Assessment for the New OSBP Inhibitor Y18501 in Pseudoperonospora cubensis and Point Mutations (G705V, L798W, and I812F) in PscORP1 that Confer Resistance

Y18501 is a new oxysterol-binding protein inhibitor (OSBPI) that shows strong inhibitory activity against Pseudoperonospora cubensis. In this study, the sensitivities of 159 Ps. cubensis isolates to Y18501 were determined, with EC50 values ranging from 0.001 to 11.785 μg/mL, indicating that a Y18501-resistant subpopulation has appeared in the field. Ten Y18501-resistant mutants were obtained by fungicide adaptation and displayed fitness equal to or stronger than their parental isolates, which suggests that the resistance risk of Ps. cubensis to Y18501 is high. The consecutive applications of Y18501 in the field resulted in the rapid resistance of Ps. cubensis and decreased control efficacy of cucumber downy mildew (CDM), which could be alleviated by compounding with mancozeb. A positive cross-resistance was detected between Y18501 and oxathiapiprolin. The amino acid substitutions G705V, L798W, and I812F in PscORP1 conferred resistance to Y18501 in Ps. cubensis, which was validated by molecular docking and molecular dynamics simulations.

Quantum Fisher information of phase estimation in the presence of indefinite causal order

Quantum Fisher information of phase estimation is studied for a single qubit which is influenced by the two generalized amplitude damping channels (GADCs) with indefinite causal order (ICO). The phase shift occurs between two consecutive applications of the GADCs. It is shown that the quantum Fisher information can be enhanced by the ICO of the quantum channels. Furthermore, even a completely incoherent state of the qubit is found to be useful for estimating the phase shift due to the ICO.