Material and Methods. In vitro pancreatic lipase activity was determined spectrophotometrically by measuring the hydrolysis of p-nitrophenyl butyrate (p-NPB) to p-nitrophenol at 405 nm, and adipogenesis was assayed in 3 T3-L1 adipocytes (by using Oil Red O staining) using P. corylifolia-dichloromethane seed extract (DCME) and individual compounds, isolated from the extract.  Effectively controlling the accumulation of adipose tissue can be a therapeutic strategy for treating obesity, which is a global problem. The present study was designed for comparative assessment of μg/ml, while, among the isolated compounds, bakuchiol exhibited a higher activity (24.2 ± 0.037%) at 100 μg/ml concentration, compared to other isolates. DCME was found to exhibit antiadipogenesis property, 75 ± 0.003% lipid accumulation, compared to the control at 100 μg/ml dose. Bakuchiol, isopsoralen, and psoralen inhibited the lipid accumulation in 3T3-L1 preadipocytes, 78.06 ± 0.002%, 80.91 ± 0.004%, and 80.91 ± 0.001%, respectively, lipid accumulation in comparison to control at 25 μM dose.  Antilipase as well as antiadipogenesis activity was displayed by both the DCME and the compounds. Maximum antilipase property was recorded in DCME (26.02 ± .041%) at 100 P. corylifolia and its active constituents. Thus, it can be concluded that P. corylifolia has the potential to treat obesity and related diseases; however, further research on dose standardization and clinical trials are required. The present study highlights the antiobesity potential of  TLC examination of the fraction was performed in a solvent ratio of 20% ethyl acetate in hexane. The combined organic solvent from different fractions was evaporated under vacuum to obtain compound 1 (0.6 g) as brown oily. The UFLC analysis of compound obtained above (compound 1) was carried out, and the chromatogram . The UFLC analysis of compound obtained above was carried out, and the chromatogram showed one single peak at the retention time of 28.5 min. Compound 2 was obtained as a white crystalline solid having melting point of 137-138°C.Compound 2 was obtained from the later obtained fractions 22-34 [solvent system up to 13% (vol/vol) ethyl acetate in n-hexane) of DCME which were then combined. The TLC analysis of the combined fractions was performed in a solvent system containing 20% ethyl acetate in hexane, after which the result was observed under UV light, and the Characteristic absorption as well as splitting pattern in 1H-NMR of compound 2 are in consonance with the 1H-NMR absorption and splitting pattern already reported by Jiangning et al. . NMR speRf value of compound 3 was found to be 0.31. The combined organic solvent was evaporated under vacuum to obtain compound 3 as white solid (0.04 g) having melting point 163-164°C. The UFLC analysis of compound 3 was carried out, and the chromatogram (Compound 3 (40 mg) was isolated from subfraction obtained by combining fractions 35-45, which was subjected to repeated CC using gradient elution with 0-15% ethyl acetate in n-hexane as analyzed by TLC. The matogram  showed oP. corylifolia seeds, bakuchiol (PC1), isopsoralen (PC2), and psoralen (PC3) was performed at 100 μg/ml, 50 μg/ml, and 25 μg/ml concentration. The percentage inhibition of PL enzyme recorded in each experiment is shown in Lipids are an essential component of human nutrition. Inhibiting the digestion of dietary fats can be a rational target for pharmaceutical intervention . The antBefore testing the extracts/compounds with the 3 T3-L1 cell line, a toxicity test was required to determine the concentration at which the extract becomes toxic, in order to rule out the possibility that the extract does not influence cell viability. The required level of viability should be greater than 90% .μg/ml. At concentrations up to 100 μg/ml, DCME of P. corylifolia showed no substantial toxicity to 3 T3 -L1 cells, as shown in μg/ml. For further tests, safe doses of DCME were kept 100 μg/ml.For toxicity analysis, 3 T3-L1 cells were treated with DCME at different concentrations 100, 125, 150, 175, 200, and 400 P. corylifolia seed on 3T3-L1 cell viability and the cells were treated with different concentrations of pure compounds, i.e., 12.5, 25, and 50 μM. At concentrations up to 25 μM, none of the isolates were found to be toxic to 3T3 -L1 cells. The viability of 3T3-L1 cells was reduced at concentrations greater than 25 μM  for 10 days with medium replacement on every alternate day. For the antiadipogenesis experiment, extracts or isolates were introduced to differentiation and maintenance medium in 0.1% DMSO carrier for up to 12 days. Control is cells treated with differentiation media plus maintenance media.The differentiation of preadipocytes to mature adipocytes is connected with the increase in the number of cells stained with Oil Red O and lipid accumulation. 3T3-L1 cells were treated with differentiation media plus 100 After staining with Oil Red O stain on day 12th, cells were imaged using an inverted microscope. The Oil Red O stain demonstrates a reduction in the quantity and size of lipid droplets accumulated in the cells treated with extract or isolates, when viewed under microscope. DCM extract as well as bioactive compounds treatment led to inhibition of adipogenesis Figures . After cObesity is currently one of the main public health concerns since it is a major contributor to the global burden of chronic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, type 2 diabetes mellitus, and certain types of cancer. Obesity-associated comorbidities can impact function and quality of life as well as mental health also . PhytochP. corylifolia. Some of its isolated compounds are bakuchiol, psoralidin, psoralen, isopsoralen, bavadin, isobavachalcone, corylin, daidzin, and genistein. The extracts and active components of P. corylifolia demonstrated multiple biological activities, including estrogenic, antitumor, antioxidant, antimicrobial, antidepressant, anti-inflammatory, osteoblastic, hepatoprotective [P. corylifolia possess antiobesity activity, and bakuchiol is a type of meroterpenoid, and psoralen and isopsoralen are coumarins (phenolic substance). Our data supports the potential of terpenoids and phenols as antiobesity agents. Moreover, in a study, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels [P. corylifolia for antiobesity activity.Phytochemical studies indicated that coumarins, flavonoids, and meroterpenes are the main components of otective , and antotective . Due to otective . In the e levels . So, thiP. corylifolia at concentrations of 25, 50, and 100 μg/ml. The results from our study indicated that DCM extract of P. corylifolia seeds, bakuchiol, isopsoralen, and psoralen exhibited inhibitory activity against pancreatic lipase which is consistent with the activity reported by other groups [One of the most extensively utilized models for examining the potential efficacy of natural products as antiobesity medicines is pancreatic lipase inhibition . Since ir groups . For comr groups . Weaker r groups .P. corylifolia seeds, bakuchiol, isopsoralen, and psoralen in 3T3-L1 adipocytes. It is interesting to note that DCME displayed a higher activity compared to the isolated compounds. This could be due the cumulative effect of other known compounds such as genistein [P. corylifolia seed extract which are known to possess antiobesity potential. There are several reports which revealed the inhibition of adipogenesis via regulation of PPARγ and C/EBPα expression in 3T3-L1 cells [P. corylifolia may inhibit adipocyte differentiation by suppressing PPARγ and C/EBPα transcriptional activity in 3T3-L1 adipocytes.When energy intake exceeds energy expenditure over time, the surplus energy is stored in the form of triglycerides in adipose tissue. An increase in cell size, cell number, or both can result in increased adipose tissue mass . Preadipenistein , 42, bavenistein , isobavaenistein , and corenistein  in the PL1 cells . P. coryP. corylifolia possesses antiobesity potential, but there are only few scientific evidences to support this claim [P. corylifolia seed extract might be due to the presence of coumarins [μg/ml concentration. Bakuchiol, isopsoralen, and psoralen decreased lipid accumulation in 3T3-L1 preadipocytes with 78.06 ± 0.002%, 80.91 ± 0.004%, and 80.91 ± 0.001% lipid accumulation, respectively, in comparison to control at 25 μM dose. These findings indicate the involvement of phytochemicals derived from P. corylifolia in regulating adipocyte differentiation, making it a promising candidate for the treatment of obesity-related diseases. This work highlights the therapeutic role of PCSE in metabolic disorders, which can help researchers across globe to analyze the various constituents responsible for antiobesity activity on specific receptors in adipose tissue. Thus, extensive research could be planned to determine the precise mode of action of the aforementioned bioactive compounds.Through our studies on PCSE, we claim that is claim . The antoumarins , flavonooumarins , etc. Pr


This effect can be modulated by task demands. Previous research established that when asked to decide if a word is an object (entity condition), a BOI effect is observed, but when asked to decide if a word is an action (action condition), there is no BOI effect. It is unclear whether the null behavioral effect in the action condition reflects top-down modulation of task-relevant sensorimotor information or the absence of bottom-up activation of sensorimotor simulations. We investigated this question using EEG. In Experiment 1 we replicated the previous behavioral findings. In Experiment 2, 50 participants were assigned to either the entity or action conditions and responded to the same word stimuli. In both conditions we observed differences in ERP components related to the BOI effect. In the entity condition the P2 mean amplitude was significantly more positive for high compared to low BOI words. In the action condition the N400 peak latency was significantly later for high compared to low BOI words. Our findings suggest that BOI information is generated bottom-up regardless of task demands and modulated by top-down processes that recruit sensorimotor information relevant to the task decision.Many theories of semantic representation propose that simulations of sensorimotor experience contribute to language processing. This can be seen in the body-object interaction effect . Words with high BOI ratings (e.g.,  In recent years theories of semantic representation and processing have diverged in the role proposed for embodied or sensorimotor information. These theories fall on a theoretical spectrum ranging from those proposing no relationship between semantic representation and sensorimotor systems to more embodied theories which propose that semantic meaning is entirely dependent on sensorimotor systems . Much evvia either top-down selection of context-relevant sensorimotor simulations or bottom-up activation of context-relevant sensorimotor simulations.There are still several unanswered questions regarding how semantic representation and processing are influenced by context. In some cases, context is thought to influence the extent to which sensorimotor simulations are activated during semantic processing. Situations that require deeper semantic processing might activate simulations to a greater extent than tasks that require only surface-level processing, for which more invariant linguistic representations are thought to suffice . AnotherBehavioral studies have found that the recruitment of sensorimotor information during language processing can be modulated by whether the task demands deep  vs. shallow  processing. Mega-studies of language processing have found that sensorimotor effects are either not present in lexical processing tasks  or tend to be weaker than sensorimotor effects observed in semantic processing tasks . HoweverIs it an animal? and Is it a concrete thing?) using the same word stimuli in both conditions. While no significant differences between conditions were observed in the participants’ behavioral data, they found greater BOLD response in brain regions associated with knowledge of living things  in the animal condition and more in the motor cortex in the concrete condition. This suggests that the nature of the sensorimotor simulations that were recruited was task dependent.There is also evidence that neural activity related to semantic processing can be modulated by task demands. ball is a high BOI word, presumably because it has many different possible bodily interactions , whereas the word cloud is a low BOI word as it refers to something with which it is more difficult for a human body to interact. In lexical-semantic processing tasks a BOI effect is consistently observed, wherein reaction times are faster to high BOI words than low BOI words  is a measure which indexes how easily the human body can interact with a word’s referent . For exaOI words . This suThe findings from thirst-cup) and the response movement was incongruent with the functional use of an object . The P2 is a positive ERP component that occurs approximately 150–250 ms after stimulus onset (peaking at ∼200 ms) and is typically located over centro-frontal regions. The P2 is modality independent, meaning that it occurs for visual, auditory, and somatosensory stimuli . A largeThe dog jumped the fence elicits a smaller N400 than The dog jumped the turtle; The N400 component is a negative ERP waveform that typically begins 200 ms after stimulus onset and lasts approximately 300 ms  vs. an action condition (Is it an action or a non-action?).In Experiment 1 we conducted a replication of the via bottom-up processes only when sensorimotor simulations are relevant to the task. Alternatively, if we observe differences in the ERP components between high and low BOI words in both conditions, this would suggest that BOI information is activated and then modulated via a top-down process, and that sensorimotor simulations are generated regardless of task demands. To allow for better understanding of the null effect that we hypothesized may occur in the action condition, we investigated differences in both mean amplitude and peak latency in the P2 and N400 components. Based on P2 and N400 literature, in the current study we hypothesized that the P2 component would be more positive for high BOI words compared to low BOI words but made no directional predictions about whether high BOI words would be associated with smaller or larger N400 amplitudes, or earlier or later peak latencies in either the P2 or N400 compared to low BOI words.If we observe differences in the ERP components between high and low BOI words in only the entity condition, this would indicate that BOI information is activated M age = 21.37, SD = 2.45) and 18 participants  in the “Action” condition .We recruited 40 participants who participated in exchange for monetary compensation ($30 for community participants) or bonus credit in a Psychology undergraduate course (student participants). All participants reported being healthy, right-handed, native English speakers with no history of severe brain injury. Three participants were excluded from analysis, one due to behavioral performance no greater than chance and two due to issues with data acquisition. Following these exclusions, the analysis included 37 participants . Participants were pseudo randomly assigned to conditions: 19 participants  in the “Entity” condition . Participants were asked to categorize each word based on the condition to which they had been assigned (“Is it an action or a non-action?” for the action condition and “Is it an entity or a non-entity?” for the entity condition). The keys “D” and “K” were used on a computer keyboard to indicate responses with the “K” key indicating the “yes” response for each condition. Participants were first given 20 practice trials with feedback on the accuracy of their categorization. Upon completion of the practice trials participants completed the 200 experimental trials. The order of word presentation was randomized for each participant.Participants sat in a comfortable chair in a sound attenuated chamber. In the semantic decision task words were presented one at a time on a computer screen using PresentationFor each trial, participants saw a central fixation cross for 500 ms followed by blank screen for a variable duration between 0–500 ms and finally the onset of the stimulus. Participants then provided their semantic decision as to whether the word referred to an action or entity dependent on their assigned task condition. The stimuli remained on the screen until the participant made a response, triggering a 1,000 ms blank screen before the onset of the next trial.Continuous EEG was recorded in a dimly lit, electrically shielded, soundproof chamber using an EasyCap (10/20 positioning system) containing 64 electrodes (using Cz as the reference). Our focus in the present experiment was on the behavioral data, but we did collect EEG data and pre-processed and analyzed those data in the same manner as described for Experiment 2, below. EEG results for Experiment 1 are presented as back, knit, smile, song, speck, stripe, and well in the entity condition (3.5% of the data) and cope in the action condition (0.5% of the data). Trials with response times faster than 200 ms or slower than 3,000 ms were also removed from the analysis . Finally, response times that were more than three standard deviations below or above an individual participant’s mean were removed .Any words for which participants demonstrated less than 60% categorization accuracy were removed from the analysis. This included To determine if task demands modulated the effect of BOI on mean reaction time or accuracy we conducted the same analyses as in F1 = 5.26, p = 0.03, η2 = 0.13; F2 = 11.18, p = 0.001, η2 = 0.11. In the entity condition high BOI words were categorized faster than low BOI words, t1(18) = 3.48, p = 0.003; t2(44) = 3.34, p = 0.002, but no significant difference was found in the reaction times for high BOI and low BOI words in the action condition, t1(17) = 1.57, p = 0.14; t2(49) = 1.01, p = 0.32. The results also included a main effect of BOI F1 = 14.06, p = 0.001, η2 = 0.29; F2 = 6.34, p = 0.01, η2 = 0.06, as responses were faster for high BOI words than for low BOI words overall.A significant interaction was observed for condition and BOI, F = 5.67, p = 0.02, η2 = 0.14; F2 = 8.63, p = 0.004, η2 = 0.09. In the entity condition responses were more accurate for high BOI words than low BOI words, t1(18) = 3.12, p = 0.01; t2(44) = 3.16, p = 0.003. No significant difference was observed between high and low BOI accuracy rates in the action condition t1(17) = 0.41 p = 0.69; t2(49) = 0.30, p = 0.76. The results also included a main effect of BOI F = 7.91, p = 0.01, η2 = 0.18; F2 = 3.99, p = 0.04, η2 = 0.04, as responses were more accurate for high BOI words than for low BOI words overall.A significant interaction was observed for condition and BOI, The behavioral results from Experiment 1 replicate those reported in A limitation of Experiment 1 was that immediate behavioral responses were collected on all trials, to replicate as many aspects of the procedure used in M age = 22.05, SD = 2.72) and 23 participants  in the “Action” condition .We recruited 55 participants who participated in exchange for monetary compensation ($40 for community participants) or bonus credit in a Psychology undergraduate course (student participants). All participants reported being healthy, right-handed, native English speakers with no history of severe brain injury. Ten participants were excluded from analysis, two due to behavioral performance no greater than chance, two due to issues with data acquisition, one due to falling outside our specified age range for participants (18–35), and five for excessively noisy ERP data. Following these exclusions, the analysis included data for 45 participants . Participants were pseudo-randomly assigned to conditions: 22 participants  in the “Entity” condition  was used and impedances were kept below 17 kOhms for the duration of the recording. The reference electrode was Cz and raw data were filtered at 0.1–55 Hz. Noisy channels were interpolated before being re-referenced to an average reference to exclude the excessive noise from the common average. The data were segmented into epochs ranging from 200 ms pre-stimulus onset to 1,000 ms post-stimulus onset. All epochs were baseline corrected using the first 200 ms portion of the epoch. Trials in which a stimulus onset was followed by a correct response were binned according to word type . Using the program EEGLAB  artifactcore and well) for which participants were accurate 59% of the time, falling just under the threshold of 60% categorization accuracy that we used in Experiment 1. However, to retain as many correct trials as possible for calculating the ERP components, we left these two words in the analysis. The data from Experiment 2 were analyzed the same way as in Experiment 1, except that in this instance only response accuracy was analyzed (with the delayed response paradigm response latencies were not interpretable). Accuracy means and standard deviations for each word type and condition are reported in In Experiment 2 there were two words in the low entity condition  = 11.68, p = 0.001, η2 = 0.21; F2 = 12.85, p < 0.001, η2 = 0.12. In the entity condition responses were more accurate for high BOI words than low BOI words, t1(21) = 4.07, p < 0.001; t2(49) = 3.59, p < 0.001. No significant difference was observed between high and low BOI accuracy rates in the action condition t1(22) = −0.67, p = 0.479; t2(49) = −1.00, p = 0.314. We also observed a significant main effect of BOI, F1 = 5.85, p = 0.020, η2 = 0.12; F2 = 6.26, p = 0.014, η2 = 0.06 and a significant main effect of condition, F1 = 4.75, p = 0.035, η2 = 0.12; F2 = 14.96, p < 0.001, η2 = 0.13.A significant interaction was observed for condition and BOI, a priori paired samples t-tests were used to compare the P2 and N400 ERP components for word types within each task condition. The ERPs representing the average across these electrodes in the action and entity conditions are presented in The P2 and N400 ERPs were extracted using ERPLAB  from a p2(2) = 27.37, p < 0.001] and for the interactions with time window , so the degrees of freedom were corrected using the Greenhouse Geiser method . Levene’s test indicated no violation of homogeneity of variance. The three-way interaction between time window, word type, and task condition was not significant, F = 2.04, p = 0.148, partial η2 = 0.05. There were also no significant interactions between time window and word type, F = 1.63, p = 0.208, partial η2 = 0.04, time window and task condition, F = 0.03, p = 0.930, partial η2 = 0.001, or word type and task condition, F = 1.35, p = 0.251, partial η2 = 0.03. There was a significant main effect of time window, F = 15.30, p < 0.001, partial η2 = 0.26, but no significant main effect of word type, F = 0.06, p = 0.816, partial η2 = 0.001 or task condition, F = 0.47, p = 0.497, partial η2 = 0.01. Pairwise comparisons between time windows revealed a significantly less positive mean amplitude between 140–180 ms  compared to between 180–220 ms , with p < 0.001. There was also a difference between 180–220 ms and 220–260 ms  with significantly more positive mean amplitude between 180–200 ms, p < 0.001.A 3  × 2  × 2  ANOVA was conducted. Mauchly’s Test indicated a violation of sphericity for the main effect of time window , so the degrees of freedom were corrected using the Greenhouse Geiser method (ε = 0.69). Levene’s test indicated no violation of homogeneity of variance. The three-way interaction between time window, word type, and task condition was not significant, F = 0.43, p = 0.653, partial η2 = 0.01. There were no significant interactions between time window and word type, F = 0.60, p = 0.552, partial η2 = 0.01, time window and task condition, F = 0.12, p = 0.884, partial η2 = 0.003, or word type and task condition, F = 0.47, p = 0.678, partial η2 = 0.004. There was a significant main effect of time window, F = 6.16, p = 0.009, partial η2 = 0.13, but no significant main effect of word type, F = 0.17, p = 0.678, partial η2 = 0.004 or task condition, F = 0.002, p = 0.965, partial η2 = 0.000. Pairwise comparisons between time windows revealed a significantly more negative mean amplitude between 350–400 ms  and 400–450 ms  compared to between 450–500 ms , with p = 0.037 and p < 0.001, respectively. There was no significant difference between 350–400 ms and 400–450 ms, p = 0.537. Planned comparisons revealed no significant differences in mean amplitude between high and low BOI words in either the action or entity conditions. See A 3  × 2  × 2  ANOVA was conducted. Mauchly’s Test indicated a violation of sphericity for the main effect of time window [χF = 2.07, p = 0.157, partial η2 = 0.05. The main effects of word type, F = 3.67, p = 0.062, partial η2 = 0.08, and task condition, F = 0.62, p = 0.435, partial η2 = 0.01, were also not significant. Planned comparisons revealed a significant difference in N400 peak latency between high BOI words  and low BOI words , in the action task condition, t(22) = 2.94, p = 0.008. No other significant differences were identified in the planned comparisons. See A 2  × 2  ANOVA was conducted. Mauchly’s Test indicated no violation of sphericity and Levene’s test indicated no violation of homogeneity of variance. The interaction between word type and task condition was not significant, The purpose of the present study was to understand the neural mechanisms associated with a behavioral, task-dependent, body-object interaction effect. In Experiment 1 we confirmed that the task-dependent BOI effect identified by In the entity condition the P2 mean amplitude was significantly more positive for high compared to low BOI words . This finding is consistent with previous research findings that processing more semantic information, such as words whose referents have more features, action words with more embodied meaning, or low BOI words in semantically rich contexts, are associated with a larger P2 component . This fiOur findings in the action condition were less clear. In the action condition we observed no differences in N400 mean amplitude  might be related to the effects we observed in this study, and there is evidence of individual differences being related to sensorimotor effects in language processing  and in bAn additional limitation is the potential influence of individual items within our stimuli set. Although we carefully matched our word stimuli on lexical-semantic variables known to influence word processing , the high and low BOI stimuli still vary on these dimensions. Unfortunately, due to the nature of our measure of neural activity (ERP), and the way the data were collected, we are not able to analyze trial-level data to account for random effects of word, nor are we able to conduct item-wise analyses on the ERP data. Item-level analyses of the behavioral data in Experiment 1 did suggest that the effects remain the same whether the analyses are conducted by subject or by item. Nonetheless, analyzing the data using a mixed-effects approach would allow for the random effects of participant  and word  to be accounted for Finally, although the ROIs we identified in our ERP analyses were based on the neural correlates of BOI effects observed in previous research , the spaIn conclusion, the present results provide new insight into the mechanisms of context-dependent semantic processing. Our findings suggest that BOI information is generated bottom-up regardless of task demands, and that task demands modulate top-down processes that recruit sensorimotor information relevant to the task decision. This supports the proposal that concept representation is multidimensional, and that conceptual processing is flexible rather than invariant. This is also consistent with more recent theories of semantic cognition  that proThe data and materials for the experiments reported here are available upon request, and none of the experiments were pre-registered.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the University of Calgary Conjoint Faculties Research Ethics Board. The patients/participants provided their written informed consent to participate in this study.AD, AP, and PP contributed to the conception and design of the study. AD collected the data. EM performed the statistical analysis. EM and AD wrote the first draft of the manuscript. All authors contributed to the manuscript revision, read, and approved the submitted version.


Aloysia citriodora Palau is popularly used to treat nervous disorders. Experimental evidence has indicated that verbascoside (VBS) isolated from A. citriodora has pharmacological potential. In this study, we evaluated the antidepressant-like effects of a hydroalcoholic extract of A. citriodora (HEAc) and VBS against lipopolysaccharide- (LPS-) induced depressive-like behavior in mice. In the pretreatment protocol , mice were pretreated with HEAc  or VBS (30 mg/kg) before the administration of LPS. In the posttreatment protocol , mice were initially administered LPS and were subsequently given HEAc  or VBS (30 mg/kg). In both treatments, the mice were submitted to an open-field test and tail suspension test (TST) at 6 and 24 h after LPS administration. The posttreatment evaluation revealed that HEAc (30 or 300 mg/kg) and VBS produced an antidepressant-like effect, as indicated by a reduction in the time spent with no movement in the TST. Moreover, HEAc (30 or 300 mg/kg) was found to reduce interleukin-6 (IL-6) levels and N-acetyl-glycosaminidase activity in the hippocampus, increase glutathione (GSH) levels in the hippocampus and cortex, and enhance IL-10 in the cortex and, at a dose of 300 mg/kg, reduced myeloperoxidase activity in the cortex. Contrastingly, no comparable effects were detected in mice subjected to the pretreatment protocol. Administration of VBS similarly reduced the levels of IL-6 in the hippocampus and increased GSH levels in the cortex. Our observations indicate that both HEAc and VBS show promising antidepressant-like potential, which could be attributed to their beneficial effects in reducing neuroinflammatory processes and antioxidant effects in the central nervous system. Despite clinical advances in the treatment of neuropsychiatric disorders, mood disorders such as major depressive disorder (MDD) are still considered an important public health problem. MDD is characterized by depressed mood and/or anhedonia, which may be related to other behavioral changes and vegetative symptoms that compromise physical and mental health . FurtherAlthough considerable attention has been focused on the multifactorial and heterogeneous disorder of depression, its etiology remains poorly understood . FurtherIn recent decades, advances have, nevertheless, been made regarding our understanding of the psychological bases underlying MDD, with observations of brain circuits revealing abnormal information processing as well as the characterization of the cellular and molecular alterations associated with this disorder. These advances have been made possible, at least in part, using rodent models, which have facilitated the investigation of molecular targets, including those stress axis abnormalities and elevated neuroinflammation .β (IL-1β), and IL-6 in several brain regions – molecules from the compounds of interest at a collision gas flow rate of 30%.The direct flow infusion of the samples was performed on the Thermo LTQ-XL apparatus (IT-MS) linear ion trap analyzer equipped with electrospray ionization (ESI) source in negative mode . Stainless steel capillary tube at 280°C, spray voltage of 5.00 kV, a capillary voltage of −35 V, tube lens of−100 V, and a 10 μg/mL), or distilled water (negative control group), were mixed with DPPH methanolic solution (400 μg/mL). Subsequently, the samples were incubated (5 min at 25°C), and the absorbance was read at 517 nm in triplicate. The values were interpolated into a standard curve of DPPH (0–60 μM) and expressed as IC50 .The free radical scavenging potential was evaluated by the decrease of 2,2-diphenyl-1-picrylhydrazyl (DPPH) absorbance, according to Xie and Schaich . The aliAdult female Swiss mice weighing 25–30 g (8 weeks) were provided by Central Animal House of Unochapecó and maintained in propylene cages under standard laboratory conditions , with free access to food and water. Food was withdrawn 12 h before the experiments and water was provided ad libitum. Several studies performed in female rodents at different stages of the estrous cycle have shown no interference in the results , 41. TheA. citriodora preparations are usually made with 15 g of plant material (approximately 2 g of dry leaves) and 150 mL of water, administered orally 2 to 3 times a day −; 1H NMR : δ 1.09 , δ 2.79 , δ 3.28 , δ 3.40 , δ 3.55 , δ 3.52–3.72 , δ 3.73–4.05 , δ 3.83 , δ 3.93 , δ 4.37 , δ 4.93 , δ 5.19 , δ 6.28 , δ 6.57 , δ 6.69 , δ 6.71 , δ 6.79 , δ 6.95 , δ 7.06 , δ 7.60 . 13C NMR : δ 17,0 (C-6″), δ 36.5 (C-7), δ 62,4 (C-6′), δ 70.9 (C-4′), δ 71.0 , δ 72 (C-2″), δ 72.4 (C-8), δ 73.9 (C-4″), δ 76.2 (C-2′), δ 81.7 (C-3′), δ 103.2 (C-1″), δ 104.4 (C-1′), δ 113.4 (C-8‴), δ 114.8 (C-2‴), δ 116.2 , δ 117.2 (C-2), δ 120.9 (C-6), δ 121 (C-6‴), δ 125.8 (C-1‴), δ 129.7 (C-1), δ 143.1 (C-4), δ 144.7 (C-3), δ 145.5 (C-3‴), δ 148.0 (C-7‴), δ 148.4 (C-4‴), δ 166.5 (C-9‴).Verbascoside was isolated in subfraction 9 of fraction EtOAc of extract of triodora . This coescribed –54. Verbm/z ratio of 623.08 revealing the deprotonated molecular ion [M–H]−, which confirmed the possible molecular mass as 624.51 compatible with the proposed molecule. Additional experiments on MS2 of the ion m/z 623 produced another ion from the main fragment at m/z 461. The ion at m/z 461 is considered to result from the loss of the caffeoyl moiety [M–H–162]− of the parental ion m/z 623. The MS3 spectrum of the ion at m/z 461 yielded a very weak ion at m/z 315 upon losing a unit of rhamnose.The negative mode mass spectrum (ESI-MS) of verbascoside (VBS) provided an μg/mL), and the positive controls  were determined based on the DPPH  elimination assay. HEAc and VBS presented IC50 of 25.59 and 11.9 μg/mL, respectively, confirming its strong antioxidant capacity in vitro. In line with expectations, gallic and ascorbic acids and quercetin also showed significant effects in reducing DPPH, with IC50 values of 3.27, 8.9, and 12.2 μg/mL, respectively.The antioxidant activities of HEAc, VBS (15–250 p < 0.05). Similarly, compared with the mice in the N group, we detected reduced locomotor activity in the mice administered HEAc  or verbascoside  when these were subjected to the OFT (p < 0.001). In contrast, mice treated with fluoxetine  showed no significant difference compared with mice in both N and Veh groups (p < 0.001)  . Accordingly, for the mice in all groups, we recorded maximum values of sickness behavior (4 points) characterized by lethargy (indicated by reduced locomotion and exploratory activity), hunched posture, ptosis, and piloerection. Subsequently, at 6 h after LPS exposure, mice in the vehicle group  showed significantly reduced locomotor activity in the OFT compared with the mice in the N group  .p > 0.05) concerning our evaluations of locomotor activity, rearing, grooming, and excretory behavior , thereby confirming the depressive-like behavior in this neuroinflammation model. However, we detected no significant differences in this regard between mice in the treatment and Veh groups . However, compared with the Veh group mice, those in the HEAc (30 or 300 mg/kg) and Flu groups were observed to have lower intensities of sickness behavior , thereby indicating a certain degree of protection against LPS  (inst LPS .p < 0.001), whereas mice receiving HEAc  and Flu were observed to complete a significantly higher number of crossings compared with the Veh-treated mice . Furthermore, mice administered VBS showed no significant difference in locomotor activity compared with the Veh group mice (p < 0.001), although we detected no significant difference between mice in the treatment and Veh groups. Moreover, with regard to the grooming and feces evaluations, we detected no significant difference among the N, Veh, and other treatment groups . However, compared with the N group mice, Veh group mice were characterized by a marked reduction in locomotor activity . However, compared with the Veh group, mice in the VBS and Flu groups showed less grooming behavior , and the number of feces produced by mice in all treatments was lower than that produced by mice in the N group (p < 0.05)  (37.01 ± 3.10 s). Results obtained for the per se group were found to be broadly comparable to those recorded for N group (45.17 ± 7.32 s), whereas, for mice administered HEAc at doses of 30 and 300 mg/kg and VBS, we detected significant reductions in the period of immobility compared with that of Veh group mice . As anticipated, mice receiving Flu showed the most pronounced treatment effect, with a marked reduction in the time spent with no movement compared with the Veh group mice (p < 0.001)  was recorded for mice in the Veh group (66.29 ± 6.31 s), which was significantly longer than that of the N group mice (< 0.001) .p < 0.05) to the N group (83.97 ± 5.09) were decreased by HEAc 300 mg/kg  compared to the Veh group (p < 0.01) . Similar results to the fluoxetine (30 mg/kg) group were found  and VBS (30 mg/kg) (more effective doses in TST) on inflammatory markers in the hippocampus and cortex were investigated. In the hippocampus, treatments with HEAc (30 and 300 mg/kg), VBS, and Flu were not able to decrease MPO levels . Elevate < 0.01) . The Vehre found .p < 0.01) with the N group (0.08 ± 0.02) and these levels were decreased by HEAc 300 mg/kg  and VBS , when compared to the Veh group  in comparison (eh group . No diffeh group . In addieh group .p < 0.01) to the Veh group (11.52 ± 1.29). On the other hand, HEAc (30 and 300 mg/kg) prevented GSH depletion  compared to the Veh group (p < 0.05 and p < 0.001). In the evaluations of SOD activity, no differences were observed between treatments and groups N and Veh  compared ( and Veh .p < 0.001), evidencing oxidative stress. However, HEAc at doses tested (30 and 300 mg/kg) as well as VBS restored GSH levels compared to group N. SOD and CAT activities as well as LPO levels were not significantly altered by HEAc and VBS, when compared with the N group  were again observed in the Veh group, compared to the N group (36.97 ± 3.62) , a bacterial endotoxin known to promote neuroinflammation. Our findings indicate that the pharmacological effects observed in mice administered HEAc (30 and 300 mg/kg) and VBS (30 mg/kg) may involve a reduction in inflammatory and oxidative parameters.Given that operties , in thisA. citriodora collected from different locations. Similarly, Skaltsa and Shammas [A. citriodora can be attributed, at least in part, to the presence of flavonoids and VBS.Our initial chemical analysis of HEAc revealed representative amounts of flavonoids consistent with the findings of Tammar et al.  who dete Shammas  isolated Shammas , Ragone  Shammas , and Qui Shammas  detected Shammas . Flavone Shammas , 62 and  Shammas , thereby Shammas . In addi Shammas . These b Shammas , 67. Thiβ and IL-6, known to be potent activators of the HPA axis, which, consequently, can modulate noradrenergic and serotonergic mechanisms [β, along with a cascade of other cytokines, including IL-6 and TNF. It is believed that these cytokines influence central neurons, resulting in certain behavioral changes [In recent years, numerous advances have been made in our efforts to gain a better understanding of the genetic, biochemical, and immunological changes involved in MDD. Recent investigations have, for example, demonstrated the interaction between proinflammatory cytokines and the hypothalamic-pituitary-adrenal (HPA) axis in patients with depression or experimental animals. Among the cytokines believed to be implicated in the association between stress and depression are IL-1chanisms –70. Furtchanisms . They ma changes , 72, 73.In this study, we aimed to mimic the action of cytokines in neuroinflammation as well as the consequent behavioral responses. To induce a neuroinflammatory response, we administered LPS to mice according to two protocols that differed in terms of the temporal application of the treatments (either before or after treatment). In the pretreatment experiment, LPS administered to mice 1 h after treatments were observed to be highly effective in promoting sickness behavior. In line with expectations, 6 h after LPS exposure, all treatment groups showed a significant reduction in locomotor activity, as evaluated by OFT. We also observed reductions in rearing and grooming behavior and the production of feces, which we speculate could be attributable to an accentuation of the sickness behavior. However, 24 h after exposure to LPS, we found that all mice had recovered from the sickness behavior, and, in TST, only mice in the Veh group showed prolonged immobility, thereby corroborating the validity of this test. Based on these findings, we can thus conclude that, at the assessed doses, HEAc and VBS do not seem to have a protective effect against the adverse effects of LPS.Although the findings of several studies have indicated the preventive effects of antidepressants or natural products on LPS-induced behavioral changes, similar therapeutic effects could not be demonstrated , 75. In κB, which regulates the genes associated with the responses of the innate and adaptive immune systems [In the posttreatment experiment, 5 h after exposure to LPS, the mice in all groups showed sickness behavior. However, we found that the intensity of depressive symptoms was lower in those mice administered HEAc (30 and 300 mg/kg) or fluoxetine (Flu), thereby providing evidence for a certain protective effect of these treatments against cell damage. At 6 h after LPS administration, mice in the Veh group showed a marked reduction in locomotor activity in the OFT. In contrast, mice receiving HEAc  or Flu treatments showed a significant increase in the number of crossings compared with those made by Veh group mice. Thus, it appears probable that, apart from the lowest dose assessed, HEAc may interfere with the immune response of mice triggered by LPS. We suspect this could be attributable to the modulation of receptor activation pathways, such as TLR4, or the transcription factors of genes that are activated and regulated via NF- systems . In addi systems . These oA notable observation was that, at 24 h after exposure to LPS, the mice began to show evidence of recovery, as indicated by the similar values obtained in the OFT for the mice in different groups. Among the mice subjected to TST, we found that, compared with Veh group mice, those administered HEAc (30 and 300 mg/kg) or VBS were characterized by reductions in the period of immobility. In this test, the time an animal remains immobile is taken to be indicative of its state of despair and is assumed to reproduce a condition corresponding to human depression. Consequently, a reduction in the period of immobility is considered indicative of an antidepressant effect . This fiIt is well established that the administration of LPS can promote the development of depressive-like behavior, and it has been proposed that this effect is associated with the induction of neuroinflammation in the cortex and hippocampus. Accordingly, preventing or ameliorating the inflammatory process could serve as an alternative approach to obtaining an antidepressant effect , 82–85.Our findings provide evidence to indicate a certain effect of HEAc against neuroinflammation, including a reduction in N-acetyl-glucosaminidase activity in the hippocampus of mice administered the 300 mg/kg dose of this extract. This indicates that the treatment might protect cells against inflammation, as macrophages are also involved at the beginning of the inflammatory process . FurtherAn additional mechanism that contributes to the anti-inflammatory activity of natural compounds is their ability to regulate the cellular redox state. This could be attributed to direct antioxidant action involving the capture of free radicals or by inducing the production of enzymes that comprise the endogenous antioxidant defense system  , 90. In Aloysia citriodora, along with its major constituent, VBS, has anti-inflammatory and antidepressant-like activities and propose that the pharmacological effects are mediated, at least in part, via a reduction in proinflammatory markers and oxidative stress. We accordingly believe that the findings of this study make an important contribution to the current understanding of the pharmacological mechanisms of this medicinal plant. In addition, our observations validate the widespread medicinal use of A. citriodora and offer the prospect of developing novel antidepressant agents.In this study, we demonstrate that the hydroalcoholic extract of the leaves of


Litoria) with broad-spectrum antimicrobial and anticancer bioactivity. It improves the efficacy of a therapeutic vaccine and immune checkpoint inhibitor therapy when injected intratumorally and inhibits TC-1 tumor growth when applied topically through intact skin in a TC-1 murine tumor model. This paper investigated the pharmaceutical kinetic profile, the tissue distribution, and the acute safety investigation of Caerin 1.9 peptide in Sprague Dawley (SD) rats. The results showed that subcutaneous injection of Caerin 1.9 at 100 mg/kg is safe and does not cause mortality or organ malfunction in the recipient rats. For the consecutive injection of F3 at 10 mg/kg, the peak concentration (Cmax) of F3 displayed at 1 hr after injection in male rats was 591 ng/mL, the average drug retention time was 0.807 hr, T1/2 was 4.58 hr, and AUC0-last was 1890 h × ng/mL. In female rats, Cmax was 256 ng/mL, with an average drug retention time of 2.96 hr, T1/2 of 1.33 hr, and AUC0-last of 740 h × ng/mL. The results showed that the concentration of Caerin 1.9 in the peripheral blood peaked at 1 hour. As injected concentration increased, T1/2 extended, and Cmax, AUC0-last, and volume of distribution at a steady state all increased. After 14 days of repeated subcutaneous injection at 10.0 mg/kg, no accumulation of Caerin 1.9 in plasma was observed. The results of tissue distribution showed that the Caerin 1.9 is below the LC-MS/MS detection threshold at a minimum concentration of 40 ng/g. In conclusion, Caerin 1.9 is well tolerated in rats and could be used with current immunotherapies for better management of solid tumors and genital warts.Caerin 1.9 is a natural peptide derived from the skin secretions of the Australian tree frog ( The human papillomavirus (HPV) is a DNA virus that transmits from person to person mainly through sexual contact. There are more than 200 subtypes of HPV. HPV is categorized into high-risk and low-risk subtypes based on their carcinogenic potential. A variety of HPV-related malignant tumors are linked to more than 12 subtypes, including high-risk HPV: HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 [Cervical cancer is one of the most common gynecological tumors in women worldwide, especially in developing countries where HPV prophylactic vaccines are less widely available . The maiNatural peptides have been attracting more attention for their potential therapeutical significance in recent years. A number of peptide-based medications have been developed, such as adrenocorticotrophic hormone isolated from pituitary glands of bovine and pig for the treatment of acute gout –8, as weLitoria genus), which have a broad spectrum of antimicrobial and antitumor properties [in vitro at a low concentration of 6.25–25 µM [in vitro [S. aureus, MRSA, A. baumannii, and S. haemolyticus. Caerin 1.9 exhibits effective antibacterial activity without inducing resistance after 30 passages, and Caerin peptides in a temperature-sensitive gel formulation inhibited bacteria growth in the skin of MRSA-infected mice [in vitro, including MCF-7 and SKBR-3 breast cancer cells, B-CPAP and CAL-62 thyroid cancer cells, and HPV+ cell lines TC-1 and Hela cells [in vitro via the TNF-α signaling pathway [Caerin peptides are a family of host defense peptides identified from the skin secretion of the Australian tree frog , and, when formed in a temperature-sensitive gel, they maintained a similar degree of bioactivity after incubation at room temperature for 30 days. Furthermore, after being heated at 100°C for 5 minutes, they are equally effective in preventing the development of TC-1 cells , 20.The acute toxicity, pharmacokinetics, and tissue distribution of Caerin 1.9 in SD rats were addressed in this work as a foundation for further exploring the feasibility of developing Caerin 1 peptide-based therapies.2), simplified as F3, was synthesized by Mimotopes Pharmaceutical Limited in Wuxi, China. The purity of F3 was more than 99.36% by Mimotopes RP-HPLC, and it was stored at −20°C a until usage. 0.9% sodium chloride injection (batch number: F18081407) purchased from Qingzhou Yaowang Pharmaceutical Co., Ltd. was used for dilution and delivery media. Protease inhibitors (batch number: SLBZ8644) and 10% neutral formalin buffer were provided by Sigma-Aldrich Trading Co., Ltd. (Shanghai).Caerin 1.9 (GLFGVLGSIAKHVLPHVVPVIAEKL-NHSprague Dawley rats (CRL: CD (SD) IGS (SPF/VAF)) were obtained from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. The rats were kept at a specific pathogen free (SPF) facility on a 12 hr light/dark cycle at 22°C with a humidity of 75%, and they were provided with disinfected standard food and water. On the day of the experiment, the male rats weighed 230–290 g and the female rats weighed 180–240 g. They were aged 7–9 weeks.The animal experiments were approved by the animal ethics committee of Foshan First People's Hospital (no. FAHGPU20160316) and Kang Long Hua Cheng Co., Ltd, where all experiments were performed (no. 20-012). The mortality, general health status, and toxic reaction symptoms of the experimental groups were documented. Before the first day of F3 administration and during the experiments, a detailed clinical observation was carried out and recorded the changes in skin, eyes and mucous membrane, respiratory system, nervous system, activity, and behaviors of the rats. The body weight was measured and recorded before the first day of administration.A single subcutaneous injection of 1.0 mg/kg F3 was given to a total of 12 SD rats . Before and after F3 administration, whole blood samples were collected at predetermined time intervals . At each time point, at least 0.5 ml blood samples were taken alternatively from 3M/3F rats.A total of 12 SD rats  received a daily subcutaneous injection of F3 at a dose of 10.0 mg/kg for 14 days. The first day of F3 administration was recorded as day 1. At least 0.5 ml blood samples were obtained alternatively from 3M/3F rats at pre- and post-F3 injection time periods .µ C18 160A (50 × 2.1 mm); gradient elution at 0.5 mL/min with 5% acetonitrile in water containing 0.1% formic acid or 95% acetonitrile in water containing 0.1% formic acid; and injection volume of 10 µL. A multiple reaction monitoring (MRM) method was selected for quantitative analysis. For analyte and internal standard, the optimum transitions were 519.50 > 129.15 (five charges) and 649.15 > 120.10 (four charges), 393.20 > 373.25, and 237.15 > 194.15, respectively. The instrumental parameters were set as follows: nebulizing gas flow was 3 L/min; heating gas flow was 10 L/min; interface temperature was 300°C; DL temperature was 250°C; and heat block temperature was 400°C.The concentration of F3 in rat plasma was determined by liquid chromatography-tandem mass spectrometry, using the method established by Kanglong Huacheng Co., Ltd. The analyte was assayed by liquid chromatography coupled with the tandem mass spectrometry (LC-MS/MS) method. The LC-MS/MS system consisted of a Shimadzu HPLC system  and an LCMS-8060 instrument . The following were the LC conditions: column, HALO ES-C18 2.7 Cmax (maximum blood concentration), Tmax (peak time), T1/2 , AUC (area under plasma concentration-time curve), Vz_F_obs (apparent distribution volume), Cl_F_obs (clearance rate), and MRTInf_obs (mean residence time).PK parameters were estimated by a noncompartmental model with the calculation model of “Linear Trapezoidal Linear Interpolation” using WinNonlin . If the plasma F3 was detected, the following pharmacokinetic parameters were measured and calculated: Thirty-six SD rats  were randomly selected and given a single subcutaneous injection of F3 at 1.0 mg/kg. Tissue samples were collected at 1, 2, 4, 8, 24, and 48 hours after F3 administration. At each time point, six rats (3 of each sex) were sacrificed. At least 0.5 ml of whole blood was collected before euthanasia, and 0.5–1.0 g of tissue was collected after euthanasia . The heaForty SD rats  were randomly divided into 4 groups . All ratTwelve SD rats  were given a daily subcutaneous injection of F3 at a dose of 10.0 mg/kg for consecutive 14 days. The first day of administration was recorded as day 1.2/30% O2 before dissection, and blood samples were taken for hematology and biochemical analysis. The collected tissue was weighed and preserved for pathological examination.For 14 days, the body weight was measured before F3 administration on the first day of the experiment and once a week thereafter, with additional measurements on the day before and on the day of the planned autopsy. Food intake was recorded once a week. The rats were anesthetized by inhalation of 70% COBlood smears were used to investigate the morphology of basophils (ABBASO), eosinophils (ABEOS), neutrophils (ABNEUT), monocytes (ABMONO), and lymphocytes (ABLYMP) in the peripheral blood. When white blood cell classification and reticulocyte count cannot be calculated directly by ADVIA 2120i, they were manually counted and calculated following the procedure published previously . The numLiver and renal functions were measured with special attention to alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), serum creatinine, total bilirubin, and urea levels. In addition, the levels of glucose, calcium, total protein, and albumin in serum samples were measured. The blood biochemical test, hematology test, and coagulation function test were detected by Hitachi 7180 automatic biochemical analyzer, Siemens ADVIA 2120i hematology analyzer, and Stargo Emo Express Hemagglutination analyzer, respectively.After blood was collected at the predetermined time points, all rats were euthanized and subjected to a comprehensive general autopsy, which included a thorough examination of the external surface of the body, all foramen, cranial cavity, external surface of the brain, chest, abdomen, pelvic cavity, viscera, cervix, and genitalia. The adrenal gland, brain , epididymis, heart, kidney, liver, ovary, spleen, testis, thymus, thyroid gland, and uterus were carefully collected, weighed, and documented before being kept in 10% neutral formalin buffer (10% NBF).The H&E staining was followed as reported elsewhere . FollowiU tests were performed to determine the difference of 95% CI (P < 0.05). The results were considered significantly credible when P < 0.05. The data were analyzed using GraphPad Prism 8.0 software [The mean and standard deviation (SD) of all variables were calculated. The data of each group was represented by the gender set of all parameters. The differences between groups were tested using univariate analysis of variance (ANOVA) and least significant difference (LSD). If heterogeneity was observed in a set of data, nonparametric Kruskal-Wallis and Mann-Whitney software .First, we looked at the pharmacokinetic characteristics of F3 when given subcutaneously at 1.0 mg/kg once or subcutaneously at 10.0 mg/kg for 14 days.Cmax of 256 ng/mL, a mean drug retention time of 2.05 hr, T1/2 of 1.16 hr, and AUC0−last of 661 h × ng/mL. In female rats, the peak concentration attained 110 ng/mL at 0.5 hr after administration. Female rats had a shorter average retention period of 1.42 hours than male rats and provided T1/2 of 0.677 hr and AUC0−last of 216 h × ng/mL. Furthermore, the steady-state volumes of distribution of male and female rats were 2431.95 mL/kg and 4402.21 mL/kg, respectively.Plasma concentrations of F3 were analyzed by HPLC, and the pharmacokinetic parameters are summarized in T1/2 of 4.58 hr, and AUC0−last of 1890 h × ng/mL. The volume of distribution was 34647.55 mL/kg at a steady state. The peak concentration of F3 in female rats also appeared at 1 hour after injection; however, their plasma level was substantially lower than that of males, with Cmax of 256 ng/mL, an average drug retention time of 2.96 hr, T1/2 of 1.33 hr, and AUC0−last of 740 h × ng/mL. Similarly, the steady-state volume of distribution that was observed in females was lower than that in males, at a volume of 25498.49 mL/kg. The results showed that F3 had a short peak time, indicating that F3 had good absorption, rapid onset, and fast elimination from the peripheral circulation. With the increase of drug concentration, the values of Cmax, AUC0−last, and the volume of distribution at a steady state increased simultaneously. As the results of a single treatment, male rats had higher peak concentration and steady-state volume of distribution than female rats.For the consecutive injection of F3 at 10 mg/kg, the peak concentration of F3 reached 591 ng/mL at 1 hour after injection in male rats, with an average drug retention time of 0.807 hr, Cmax and AUClast in females and males after repeated injections of F3 were 2.309 and 2.554, respectively, after the first day of administration. On the 14th day, the postinjection ratio was 1.063 in females and 1.152 in males. After first dosing, Cmax and AUClast in male rats were higher than those in female rats, while, after repeated doses, both male and female rats had similar Cmax and AUClast . After repeated subcutaneous injection, F3 showed a lower apparent half-life of elimination and a shorter circulation time, suggesting that there is no F3 accumulation in the plasma , suggesting that the concentration was below the lower limit of quantification (LOQ in tissues was 40–80 ng/g).F3 concentrations in plasma samples peaked 1 hour after administration at 165.18 ± 46.54 ng/mL in males and 174.30 ± 42.96 ng/mL in females and subsequently steadily declined. After 2 hours, the mean plasma F3 concentration was 104.33 ± 25.52 ng/mL in males and 49.68 ± 1.71 ng/mL in females. At the 4th hr, the plasma concentrations dropped to 20.00 ± 9.73 ng/mL in male rats and to 19.42 ± 5.96 ng/mL in female rats.The acute toxicity of F3 was then examined with single and repeated subcutaneous injections. PBS, a single dose of F3 , or repeated doses of F3 for 14 days  were randomly administered subcutaneously to rats. As described above, plasma and tissue samples were collected fifteen days after the first dose of F3.A single or repeated subcutaneous injection of F3 had no effect on food intake, body weight, and weight change in rats. During repeated dosage, the body weights of both male and female rats increase proportionately. In any of the cases, no rats receiving F3 were found dead or dying by cage observation, and all rats were in a healthy mental state with actively free moments. The changes in the rats' fur, eyes, and mucosa, along with their respiratory system, circulatory system, nervous system, as well as the behaviors were meticulously documented. All subjects showed no abnormalities after receiving a single subcutaneous injection of F3 at 1.0 mg/kg or 10.0 mg/kg. However, one male and two female rats on day 8 and two female rats on day 15 developed dorsal scabs after receiving a single dose of 100.0 mg/kg. During the repeated-dose acute toxicity investigation, scabs were discovered at the injection site in one female rat, three female rats, and two male rats on the 8th, 12th, and 15th days, respectively. These phenomena were considered to be related to F3 administration.Biochemical examination on day 15 after F3 single-dose administration revealed no abnormal parameters in male or female rats that received a single injection of different doses of F3 (Tables S1 and S2), including hepatic and renal functions as well as other important parameters . In compIn rats given 10.0 mg/kg of F3 once per day for 14 consecutive days, no abnormal blood biomedical parameter values were found, indicating that the body function was maintained in a normal physiological condition (Tables S1 and S2). Meanwhile, significant differences in several blood indexes were observed when comparing the values of the experimental rats to those of the control rats: the rats that received repeated dosages exhibited lower ALP and ALB and higher ALT. The increase of lactate dehydrogenase (LDH) in some male rats was considered an occasional phenomenon unrelated to F3. Other blood biochemical indicators in the blood were within the normal limits.The hematological and coagulation indexes of rats were unaffected by single subcutaneous injections of different doses of F3  or repeated injections of F3 at 10.0 mg/kg for 14 days Tables .Neither single subcutaneous injection of different doses of F3  nor 14-day subcutaneous injections of F3 at 10.0 mg/kg affect the weight of the organs, the ratio of viscera to the body, and the ratio of viscera to the brain Tables  and 7.Gross necropsy showed that the subcutaneous injection of F3 at 100.0 mg/kg caused skin scab and thickening at the administration site in all male rats and four female rats. One male rat, in particular, showed scattered bleeding at the injection site, which was thought to be related to the local administration of high levels of F3.All rats who received F3 at 10.0 mg/kg for 14 days experienced diffuse subcutaneous bleeding at the injection site. In addition, thickening skin was observed in all males and four females, with scabby skin in one male and three females. The accumulation of F3 local dosage was considered to be the cause of the aforementioned events.There were no apparent abnormalities, such as excessive hematopoietic cell infiltration, hemorrhage, or structural changes, in essential organs from rats treated with F3 for 14 days at 10.0 mg/kg under histopathologic examinations .In this study, we found that subcutaneous injection of Caerin 1.9 was well tolerated in SD rats. No accumulation of Caerin 1.9 in plasma was observed after 14 days of repeated subcutaneous injection of 10.0 mg/kg. Except in the peripheral blood, Caerin 1.9 was barely detectable in essential organs and tissues.s.c. injections of F3, even when the single dose was up to 100 mg/kg. F3 had no influence on absolute and relative organ weight, as well as gross and histopathological changes in the heart, brain, spleen, liver, kidney, colon, testis, and ovary, showing that F3 did not induce any significant abnormalities. H&E staining of the heart, liver, kidney, and other important organs remained in normal morphology  is safe, does not cause death in rats, and has no significant side effects on organ weight, hematological and biochemical parameters, and no significant abnormalities in the gross and histopathological appearance of major organs, with the exception of skin scab induced by a high dose or repeated injections. Caerin 1.9 could be an ideal candidate for combination with current therapies for better management of solid tumor .


To analyze the genotypes and phenotypes of a child with developmental dysplasia of the hip (DDH), developmental delays, recurrent fever, hypothyroidism and cleft palate.G-banding karyotyping analysis and next-generation sequencing (NGS) were performed for the patient. The genotypes of the parents of the patient were verified by copy number variation analysis and Sanger sequencing to determine the source of variations.HSPG2 mutations . One mutation was inherited from the father, and the other was inherited from the mother.The karyotype of the patient was 46, XX. A 10.44 Mb deletion (chr18:67562936-78005270del) at 18q22.2q23 was found by NGS. We identified 2 HSPG2.This is the first 18q deletion syndrome case accompanied by DDH. Most phenotypes of this patient, such as developmental delays and cleft palate, may be related to the 18q22.2q23 deletion, but no variants in genes related to DDH were found in this deletion region. DDH may be related to mutations of  Its incidence rate is approximately 1%, and this rate is approximately 6 times higher in females than in males . The manThis patient presented in this case is a female who was 89 days old. She was born to a G1P1 mother by cesarean section due to a breech position at 38 weeks. Her birth weight was 2470 g. She was hospitalized in our hospital because her “body weight increased slowly for 73 days and she had recurrent fever for 11 days.” On the 16th day after birth, the patient was found to have a slow increase in body weight. The thyroid function was considered normal. However, she presented with hypothyroidism, as she had elevated levels of FT3, FT4, and TSH. FT3 was 3.81 pmol/l , FT4 was 11.57 pmol/l , and TSH was 82.35 µIU/ml . Thyroid ultrasound showed increased thyroid blood flow. Left thyroxine  was administered orally. On the 56th day after birth, the patient was diagnosed with bilateral dislocation of the hip (DDH) and fixed with a DDII sling. On the 78th day after birth (11 days before admission), she began to have recurrent fever without coughing, vomiting, or diarrhea. Her parents were not in a consanguineous marriage. Her mother was in good health but suffered from cleft lip. Her father was in good health. Physical examination revealed a temperature of 38.3 °C, a pulse of 145 beats/min, a resting heart rate of 60 beats/min, a weight of 3 kg, a body length of 54 cm, and a head circumference of 38 cm. The patient was in poor spirit. The skin was scattered with patterns. The subcutaneous fat was thin and had poor elasticity. Cleft palate, strabismus, hypotonia were observed. The lower limb was fixed by a DDII sling. Joint ultrasound showed bilateral hip dislocation. Cardiac ultrasound showed patent foramen ovale and tricuspid regurgitation. Brain MRI showed encephalomalacia in the right basal ganglia. Internal auditory canal MRI showed bilateral large vestibular aqueduct dilation, and the brainstem auditory evoked potential examination showed that both ears failed. Chest CT showed a small amount of inflammatory changes in the lungs. The serum IgA was 0.09 g/l , IgG was 4.95 g/l , IgM was 0.4 g/l , and IgE was < 15 IU/ml . Routine blood examination indicated moderate anemia (Hemoglobin was 8.4 g/dl). The thyroid function, CRP, PCT, ESR, routine urine, routine stool, and liver and kidney function tests and the blood gas analysis were generally normal. There was no bacterial growth in multiple blood bacterial cultures, no abnormality in peripheral blood smears, no abnormality in 3-h video EEG, and no abnormality in the G-banding karyotyping analysis  by oral administration and piperacillin sodium and tazobactam sodium  by intravenous administration. The patient’s spirit improved slightly, and her thyroid function was normal. However, she still had a fever. The temperature fluctuated between 37.8 and 39.0 °C. Her skin was dry and she was not sweating. The effect of physical cooling and antipyretics was poor. Due to the patient’s clinical manifestations, we highly suspected that the patient had hereditary diseases. To clarify the diagnosis, we obtained the patient’s blood samples for NGS after obtaining the consent of the patient’s parents.Genomic DNA was extracted from the peripheral blood of the patient and her parents, and the whole genome library was prepared by the Beijing MyGenostics company. The gene exon region and its upstream and downstream 50 bp region of the patient and her parents were sequenced by Illumina HiSeq X ten high-throughput sequencing platform, DNBSEQ (DNBSEQ-T7) sequencer, with a read length of 150 bp, sequencing mean depth of 100X.The data were filtered and compared by the cutadapt (1.16), BWA (0.7.12), and GATK (4.0.8.1) MarkDuplicates software by Beijing MyGenostics Company after sequencing. The CNV was calculated mainly according to the read depth method. All suspicious deleted or repeated regions that were obtained were compared with OMIM, genereviews, decipher, ClinVar, DGV and other databases to obtain the phenotypic information related to the chromosomal regions.PARD6G, MBP, TIMM21, CNDP1, FBXO15, NETO1, KCNG2, ZNF407, NFATC1, ZADH2, TXNL4A, CYB5A, ATP9B, SMIM21, ZNF236, CBLN2, C18orf63, GALR1, SALL3, SLC66A2, CNDP2, DIPK1C, HSBP1L1, ADNP2, RTTN, CD226, and SOCS6 genes. Moreover, we found 108,522 variants, including HSPG2 mutations  (Table NGS showed that the long arm of chromosome 18 had an approximately 10.44 Mb copy number loss at 18q22.2q23 (67562936-78005270del)  [We did not find any mutations in genes that were related to the recurrent fever phenotype in this patient. Some researchers believe that recurrent fever may be related to the lack of IgA , but thituration . Diseases (AITD) . Howevers (AITD) ; in thisCX3CR1, UFSP2, HSPG2 and ATP2B4 [HSPG2 in this patient. The variant at the exon site, c.2244c > A, p.h748q, was a novel mutation from the father who had no clinical manifestation of DDH. The variation at the intron site, c.11671 + 154insa, was located in the deep intron region and was unlikely pathogenic. HSPG2 encodes for perlecan, a large proteoglycan that plays an important role in cartilage formation, cell adhesion, and basement membrane stability. The diseases related to HSPG2 mutations mainly include dyssegmental dysplasia Silverman-Handmaker type (DDHS) and Schwartz Jampel syndrome type 1, both of which are autosomal recessive diseases [HSPG2 mutant (C1532Yneo) mice [HSPG2 mutant mice demonstrated weight loss and DDH. Considering that the genetic mode of inheritance of this disease may be autosomal dominant with incomplete penetrance, the possibility that the DDH in this case is caused by HSPG2 mutations has not yet been excluded. But, a replication analysis of 250 sporadic samples with Sanger sequencing by Xu et al. [The patient in this study also had a phenotype that had not been reported in patients with 18q deletion syndrome. The pathogenesis of DDH may be congenital or acquired. Acquired factors mainly include breech delivery. This patient was breech delivered, but she was born by cesarean section without birth injury factors. Therefore, DDH in this case was unlikely to be related to breech delivery. The underlying genetic mechanisms of DDH are not clear at present. The possible genetic mode may be autosomal dominant inheritance with incomplete penetrance, which may be related to variants of d ATP2B4 , 21–23. diseases . Schwartdiseases , 27. Theeo) mice  confirmeu et al.  indicateHSPG2 mutations in this case. The relationship between phenotypes and genotypes in 18q deletion syndrome need to be further studied.18q deletion syndrome has many common phenotypes with robust differences in clinical manifestations. Most abnormal phenotypes are caused by the deletion of coding genes in the deletion region, but the mechanisms of a few phenotypes are still unknown. Based on the examinations performed in this case, we speculate that the recurrent fever was not related to IgA deficiency. DDH is a newly reported phenotype in a patient with 18q deletion syndrome, which may be related to


To analyze the growth disturbance after distal tibia physeal fracture in children.Data about children with distal tibia physeal fractures between September 2015 to September 2018 were collected, including age, gender, affected side, Salter–Harris classification, initial maximal displacement, with or without fibula fracture, open or closed reduction, the method of fixation, time to surgery, blood loss, duration of operation, and complications. Patients were placed in the growth disturbance group when leg length discrepancy was equal to or greater than 1.5 cm, or when they had more than 5 degrees of varus or valgus deformity. Others were placed in the no-growth disturbance group.p = 0.004) and fibula fracture (p = 0.011) between the two groups. More patients had Salter–Harris types III and IV fractures in the growth disturbance group than in the no-growth disturbance group (p = 0.043).A total of 143 patients (96 boys and 47 girls) were enrolled in this study. The length of the follow-up periods averaged 29.34 ± 7.46 months (26 to 61 months). Among the total of 143 patients, the incidence of growth disturbance was 15.39% (22/143). The no-growth disturbance group consisted of 121 patients (84 boys and 37 girls), with a mean age of 11.50 ± 3.20 years, and there were 68, 52, and 1 injuries to the left, right, and bilateral sides, respectively. The average maximal displacement was 5.51 ± 3.18 mm, and 27.27% (33/121) of patients also had a fibula fracture. The growth disturbance group contained 22 patients (12 boys and 10 girls) with a mean age of 9.32 ± 3.56 years, and there were 12, 10, and 0 injuries on the left, right, and bilateral sides, respectively. The average maximal displacement was 5.77 ± 4.89 mm, and 45.45% (10/22) of patients also had a fibula fracture. There was a significant difference in age (Children with Salter–Harris types III and IV fractures, younger children, and children with fibula fractures all have a higher incidence of growth disturbance after distal tibia physeal fractures.Level III-Prognostic study. Distal tibia physeal fractures are a relatively common physeal injury and are the second most common injury in children after the distal radius physis , 2. DistMultiple factors, including the cause of injury, fracture type and location, initial displacement, Salter–Harris classification, number of attempted reductions, open or closed reduction, and residual displacement after the intervention, are thought to be associated with growth disturbance , 11–13. Data about children with distal tibia physeal fractures who were treated in Fuzhou Second Hospital Affiliated with Xiamen University between September 2015 to September 2018 were collected. All patient files were reviewed with the approval of the hospital. Patients were placed in the growth disturbance group when the difference in their leg lengths was equal to or greater than 1.5 cm or more than 5 degrees of varus or valgus deformity. Otherwise, they were placed in the no-growth disturbance group.All patients were further divided into early and delayed operation groups. According to Rang and Salter , 15, patThe following data were extracted from the database: age, gender, affected side, Salter–Harris classification, initial maximal displacement, the presence of fibula fracture, open or closed reduction, method of fixation, time to surgery, blood loss, duration of operation, and complications.Age less than 16 years.Diagnosed with distal tibia physeal fracture.Residual displacement less than 2 mm after surgery, measured by scale with a 2 mm diameter steel ball or K-wire nest to the ankle joint.Follow-up more than 12 months.The inclusion criteria were as follows:Peripheral vascular diseases.Neuromuscular diseases.Metabolic bone disorders.Pathological fractures.Residual displacement more than 2 mm after surgery.The exclusion criteria were as follows:t-test or one-way analysis of variance at a 5% significance level (2.5% on each side). Descriptive statistics of categorical variables were represented as frequency and percentage. A Chi-square test was used to compare the differences in rates among different groups at a 5% significance level (2.5% on each side).SPSS 22.0 software was used for all statistical analyses. Descriptive statistics were conducted for continuous variables using mean ± standard error (SE). A comparison test between two independent or more than two groups was made using a two-sided Student’s A total of 143 patients (96 boys and 47 girls), with an average age of 11.19 ± 3.34 (range from 2.8 to 16) years, were enrolled in this study. The follow-up periods averaged 29.34 ± 7.46 months (26 to 61 months). The overall incidence of growth disturbance was 15.39% (22/143); among them, 21 cases had varus or valgus deformities greater than 5 degrees, and 1 case had a limb shortening exceeding 1.5 cm. However, no infection, nonunion, or osteonecrosis was observed in any patient.p = 0.004), but no significant difference in the factors described above (Table The no-growth disturbance group contained 121 patients (84 boys and 37 girls), with a mean age of 11.50 ± 3.20 years, and 68, 51, and 1 cases on the left, right, and bilateral sides, respectively. The average maximal displacement was 5.51 ± 3.18 mm. The growth disturbance group contained 22 patients (12 boys and 10 girls) with a mean age of 9.32 ± 3.56 years, and 12, 10, and 0 cases on the left, right, and bilateral sides, respectively. The average maximal displacement was 5.77 ± 4.89 mm, and the average comprehensive displacement was 5.05 ± 2.38 mm. There was a significant difference in age between the two groups (p = 0.043)  Fig. .Table 2Pp = 0.011). Differences in open or closed reduction, type of fixation, duration of operation, and blood loss were not significant between the two groups. Forty-four cases received K-wires, 76 received screws, and 1 received plates in the no-GD group; 8 cases received K-wires, 14 received screws, and 0 received plates in the GD group. Differences between the two groups were not significant.Among the no-growth disturbance group, 27.27% (33/121) of patients also had fibula fractures, while 45.45% (10/22) of patients in the growth disturbance group also had fibula fractures, which was significantly different (p > 0.05)  and the delayed operation group (3/20)   Fig. .p = 0.011). Patients with fibula fractures could have suffered more significant injuries. Significant injuries often manifest as larger initial displacements but can also be accompanied by other fractures.We also found that the growth disturbance group (12/22) Table  was morePatients were classified either into an early operation group or a delayed operation group based on the methods used by Rang and Salter , 14. TheThis study had some limitations. It was a retrospective study, and the number of cases was limited. Growth disturbance from a physeal fracture is typically evident 2 to 6 months after the injury, but it may not become obvious for up to 2 or more years after the injury. Therefore, follow-ups should be extended to near skeletal maturity. However, Stenroos et al.  suggestePatients in the growth disturbance group were significantly younger and more likely to be Salter–Harris types III and IV than patients in the no-growth disturbance group. Patients who also had fibula fractures could have a higher incidence of growth disorders.


To evaluate the visual performance and clinical outcomes after implantation of Lucidis EDOF IOL following cataract surgery.  In this retrospective study, medical records from all enrolled patients were analyzed, and the following information was extracted retrospectively over 3 months following surgery.  We reviewed retrospectively 181 eyes of 98 patients, who underwent cataract surgery with Lucidis extended depth of focus IOL. p = 0.0001). Between the baseline and 3-month postoperative measures, monocular distance BCVA improved by an average of 0.16 ± 0.13 logMAR (p = 0.0001). Monocular UDVA 1 and 3 months postoperatively was 0.08 ± 0.1 logMAR and 0.067 ± 0.08 logMAR, respectively. 1-Month postoperative binocular UDVA was 0.036 ± 0.05 logMAR, binocular UIVA was 0.1 ± 0.08 logMAR, and binocular UNVA was 0.12 ± 0.14 logMAR. 3-Month postoperative binocular UDVA was 0.038 ± 0.05 logMAR, binocular UIVA was 0.09 ± 0.1 logMAR, and binocular UNVA was 0.16 ± 0.14 logMAR.  44 patients were males (45%) and 54 were females (55%). The average age of the study population was 68 ± 11 years. The mean preoperative BCVA (logMAR) was 0.19 ± 0.18. The mean root mean square (RMS) high order aberration (HOA) was 0.18 ± 0.1. Monocular BCVA results were 0.02 ± 0.04 (logMAR) and 0.028 ± 0.04 (logMAR) 1 month and 3 months postoperatively, respectively. Between the baseline and 1-month measures, monocular distance BCVA improved by an average of 0.17 ± 0.14 logMAR ( Lucidis EDOF IOL achieves good visual performances in all distances. Cataract surgeons are constantly in search of better refractive postoperative outcomes and better visual performances. New designs of intraocular lens (IOLs) help to achieve a more optimal visual performance and patient satisfaction.Normally, the surgeons treat cataract patients by replacing the lens with a monofocal posterior chamber IOL. Therefore, patients should make a decision preoperatively which range of vision they prioritize postoperatively.The introduction of the newest IOLs with extended depth of focus (EDOF) technology enabled a relatively good visual performance in intermediate distances as well as for far and near distances –6. TheseFurthermore, EDOF IOLs have been found to be associated with fewer halos and less contrast sensitivity loss than traditional multifocal IOL technology .The basic principle of such IOLs is to create a single-elongated focal point to enhance the depth of focus, to eventually eliminate the overlapping of near and far images, as seen with other IOLs .The Swiss innovation of the Lucidis IOL  is a new type of refractive/EDOF hybrid IOL involving a central aspheric element surrounded by an outer refractive ring .The central aspheric zone in an area of 1 mm acts as an axicon, so that the emerging light forms a Bessel beam, resulting in a beam of focal fields that allow a continuous vision from intermediate to short distances. This aspheric geometry does not generate any additional spherical aberration to the lens.The aim of the current study is to evaluate the visual performance and clinical outcomes with Lucidis EDOF IOL.This is a single-center, retrospective study of 98 patients (181 eyes) who underwent implantation of the Lucidis EDOF IOL  during cataract surgery by 4 experienced surgeons between 2019 and 2022.We performed a monocular unilateral analysis of preoperative and postoperative best corrected visual acuity (BCVA) and monocular uncorrected distant visual acuity (UDVA) of each eye. Uncorrected near visual acuity (UNVA) and uncorrected intermediate visual acuity (UIVA) were analyzed bilaterally. UDVA was also analyzed bilaterally for the purpose of visual acuity reporting.Institutional board approval of the study and patients' consents were obtained. No conflicts of interest to be reported for this study.D, age <18 years, and no previous corneal surgery.Exclusion criteria were the presence of a concomitant ophthalmic condition, including age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, corneal opacities, or astigmatism of >1.00 The decision to perform cataract surgery and the choice of the IOL were based on clinical indications.Lucidis is a single-piece foldable multizone refractive/aspheric IOL, with a 360° square edge design and closed-loop haptics. The lens has a 6.0 mm optical diameter and a total diameter of either 10.8 mm or 12.4 mm. It is made from hydrophilic acrylic with a 26% water content. Optically, the Lucidis IOL uses both refraction and an aspheric element—the Axicon. The 1 mm aspheric zone occupies the center of the IOL and is surrounded by a 6 mm refractive ring.All surgeries were performed under local anesthesia and a venous sedation with Rapifen and propofol on demand. All interventions were performed using the same standard protocol on a temporal side, 2 mm main incision, and phacoemulsification machine ; for all FLACS, a femto laser LDV Z8  was used.A foldable Lucidis IOL was implanted in the capsular bag. No Lucidis IOLs were implanted in the sulcus.Patients attended follow-up visits as a local protocol, at 1 day, 7 days, 1 month, and 3 months postoperatively. Additional appointments were planned at the surgeon's discretion. At each of the follow-up visits, the results were recorded in the patients' medical notes. 1-Month postoperative follow-up was done for 181 eyes, and 3-month postoperative follow-up was available for 78 eyes.For refractive purposes, we tested monocular best-corrected visual acuity (BCVA), monocular and binocular uncorrected distant visual acuity (UDVA) at 6 meters, and binocular uncorrected visual acuity for near and intermediate distances  at 40 cm and 80 cm in photopic conditions. The surgeons performed the visual acuity testing in the same room and with the same ambience illumination using a Snellen decimal chart. The ophthalmologists recorded their observations following a slit-lamp examination as well as any subjective complaint or adverse event.Statistical analysis was performed on all available 1-month data. Quantitative and qualitative variables are described in terms of sample size, mean, standard deviation, median, range, and missing data.t-test to compare two means, and a Wilcoxon test to compare nonparametric continuous data. Results were considered statistically significant if p < 0.05.Excel  was used for data analysis. The following analyses were performed for all parameters: an independent p < 0.05.SPSS version 26  was used for the ANOVA test and regression analysis for independent risk factor identification. Results were considered statistically significant if 181 eyes of 98 patients were included, all of which had up to 3-month data. In the cohort, 44 patients were males (45%) and 54 were females (55%). The average age of the study population was 68 ± 11 years. The mean preoperative BCVA (logMAR) was 0.19 ± 0.18, as shown in p = 0.0001). Between the baseline and 3-month postoperative measures, monocular distance BCVA improved by an average of 0.16 ± 0.13 logMAR (p = 0.0001).Monocular BCVA results were 0.02 ± 0.04 (logMAR) and 0.028 ± 0.04 (logMAR) 1 month and 3 months postoperatively, respectively. Between the baseline and 1-month postoperative measures, monocular distance BCVA improved by an average of 0.17 ± 0.14 logMAR  between 0.13 and +0.13D, as shown in 3 months postoperatively, 27% of the eyes had emmetropic spherical equivalents (SE) between 0.13 and + 0.13D. The mean monocular UDVA for that range of postoperative cylinder was 0.078 ± 0.09 logMAR.1 month postoperatively, 57% of the eyes had a cylinder value <-0.5D, as seen in 3 months postoperatively, 38% of the eyes had a cylinder value <−0.5Perioperative and postoperative negative outcomes included complications, glares, or halos reported by patients and discomfort with near vision that requiring spectacles or an eventual add-on operation, as seen in In our study, we demonstrated good results for far, intermediate, and short uncorrected visual acuity for eyes after implantation of Lucidis EDOF IOLs up to 3 months postoperatively.Nowadays, we are familiar with many types of IOLs with EDOF characteristics that were described under the term EDOF.Among these are pure EDOF IOLs  and EDOF IOLs using the pinhole effect . There are also hybrid MF/EDOF IOLs that are further subdivided to diffractive/EDOF IOLs , refractive/EDOF IOLs , and refractive-diffractive/EDOF IOLs  .The particularity of the Lucidis IOL is the central aspheric zone in an area of 1 mm that acts as an axicon, resulting in a beam of focal fields that allow a continuous vision from intermediate to short distances. This aspheric geometry does not generate any additional spherical aberration to the lens.Furthermore, the main benefit of the design of the Lucidis IOL is to provide additional visual comfort at near and intermediate distances , 10. NotEDOF IOLs  were previously demonstrated to perform similarly to multifocal IOLs  for far and near distances, with superiority at the intermediate level .Compared to Trifocal IOLs (AT LISA tri 839MP IOL), for the intermediate distance visual performance, EDOF IOL (Symfony IOL) was also found superior .EDOF IOLs were found to provide not only a subjective satisfaction but also a good quality of uncorrected postoperative visual acuities at all distances , 14.In our study, monocular UDVA 1 and 3 months postoperatively was 0.08 ± 0.1 logMAR and 0.067 ± 0.08 logMAR, respectively.In a meta-analysis of 24 studies, Rosen et al. demonstrated a mean UDVA of 0.11 logMAR, achieved after multifocal IOL implantation . HogartyFurthermore, in our study, we found binocular UIVA of 0.1 ± 0.08 logMAR and 0.09 ± 0.1 logMAR 1 and 3 months postoperatively, respectively. Our results for the intermediate uncorrected visual acuity were comparable to those reported by Cochener et al. for TECNIS EDOF IOL . The autIn addition, we found that binocular UNVA was 0.12 ± 0.14 logMAR and 0.16 ± 0.14 logMAR, 1 and 3 months postoperatively, respectively, which were also comparable to previous reports of TECNIS Symfony IOL of 0.28 logMAR at the near range , the latIn our study, we also demonstrated an emmetropic spherical equivalent in 24% of the eyes (−0.13 and + 0.13 D) and 27%, 1 and 3-months postoperatively, respectively. The SE corresponded to a mean monocular UDVA of 0.07 ± 0.09 logMAR and 0.07 ± 0.09 logMAR, 1 and 3 months postoperatively, respectively. On the other hand, Cochener et al. found emmetropic SE outcomes for TECNIS Symfony  for 8% of the eyes (17).D, 1 and 3 months postoperatively, respectively. The corresponding mean monocular UDVA was 0.078 ± 0.09 logMAR and 0.08 ± 0.1 logMAR, 1 and 3 months postoperatively, respectively, while Cochener showed that, for TECNIS Symfony IOL, 56% of the eyes had a postoperative cylinder of less than 0.5 D (17).In addition, in our study, we demonstrated that 57% and 38% of the eyes had a cylinder value of less than −0.5 In our study, only 5% of the patients complained of visual aberrations during the follow-up period, 4% complained of diplopia, 20% were provided with reading glasses for a suboptimal postoperative UNVA, and 3% opted for an additional Add-On IOL , a line of sulcus-fixated silicone lenses.However, it was previously shown that dysphotopsias such as halos were inevitable in EDOF IOLs and increase with higher near addition powers , 19.Preoperatively, it is important to consider the specific patient's visual needs as well as the extent to which they are willing to accept such optical side effects.D anisometropia.If, for example, the patients would not tolerate dysphotopsias and were willing to accept glasses for reading, one possibility with EDOF IOLs could be micro monovision of −0.75 While our study focused on virgin eyes undergoing cataract surgery with Lucidis EDOF IOL implantation, future studies are warranted to evaluate dysphotopsia and spherical aberration incidence in eyes with a previous refractive surgery  that are scheduled to have cataract surgery and an EDOF IOL implantation. Any previous refractive surgery can be associated with a more challenging IOL power calculation, as well as a postoperative refractive surprise and corneal instability (postoperative astigmatism).For such less convenient conditions for an EDOF IOL consideration, Meduri et al. suggested some perioperative methods such as stabilizing sutures that lowered the risk of dehiscence as well as the postoperative astigmatism , 21.Furthermore, Baartman et al. found that for eyes with previous radial keratotomy that had undergone phacoemulsification with implantation of the TECNIS Symfony EDOF IOL, there were good visual outcomes and a subjective satisfaction of the patients .The current study has several limitations. Firstly, its retrospective nature. Secondly, this study lacks long-term follow-up with only 3-month data available that does not allow for analysis of potential long-term complications.The retrospective nature of the study did not allow to include corrected near and intermediate visual acuity which would have allowed the confirmation as to whether the previously documented performance of this IOL for distance vision was due to its design or to a myopic postoperative spherical equivalent. Nor did it allow to include a baseline UCVA measured preoperatively or the postoperative contrast perception.In conclusion, in our study, we demonstrated good visual outcomes for Lucidis EDOF IOL for all ranges of vision. Furthermore, investigations of the long-term performance of this IOL is warranted in future studies.