To investigate the efficacy of high-volume hemofiltration (HVHF) in the treatment of severe acute respiratory distress syndrome (ARDS) caused by sepsis and its effect on serum levels of miR-126, miR-184, and MAP1-LC3.  From July 1, 2015 to December 31, 2021, patients with severe ARDS caused by sepsis who were admitted to our hospital were retrospectively analyzed. Patients who received conventional treatment were summarized into the control group, and those who received HVHF were summarized into the study group. The treatment effects of the two groups were compared. α, miR-126, miR-184, and MAP1-LC3 were significantly lower in the study group , whereas PEF, FRC, TEF25%, heart rate, mean arterial pressure, and blood oxygen were significantly higher in the study group .  Ninety-five qualified patients were retrieved, with 42 patients in the control group and 53 patients in the study group. After treatment, the levels of IL-6, IL-10, TNF- HVHF has a good clinical effect on improving patients with severe ARDS caused by sepsis and can improve the pulmonary function of patients. Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is characterized by a high mortality rate and is commonly seen in intensive care units , 2. The From July 1, 2015 to December 31, 2021, patients with severe ARDS caused by sepsis who were treated in our hospital were retrospectively analyzed. All patients in this study signed the informed consent form. This study was approved by the Institutional Ethical Committee of our hospital.2/Fi O2 ≤ 100 mm·Hg; PEEP ≥ 5 cm H2O; onset time ≤ 72 h, and oxygenation index ≤ 100 [Inclusion criteria were as follows: the clinical diagnosis was severe ARDS caused by sepsis ; severe Exclusion criteria were as follows: complicated with malignant diseases, mental illness, drug allergies, etc.; patients aged ≤18 years or ≥75 years old; patients with liver or renal insufficiency; or patients with previous pulmonary underlying diseases.Patients in the conventional treatment received mechanical ventilation, anti-infection, moderate fluid replacement, antishock, nutritional support treatment, etc. Patients in the research group received continuous HVHF on the basis of conventional treatment. The vascular access was established through the femoral vein, the replacement fluid was bicarbonate, the replacement fluid was diluted 80% before use, the flow rate of hemofiltration was 45 ml/kg/h, and heparin was used for anticoagulation. Continuous HVHF treatment was carried out for 24 hours, at least 3 days.The inflammatory cytokines, lung function, serum miR-126, miR-184, MAP1-LC3 as previously reported [χ2 test , and the measurement data were analyzed by t-test (mean ± SD). A two-tailed P < 0.05 was determined to have statistical significance.The data in this experiment were analyzed by the SPSS21.0 software package , in which the count data were analyzed by There were 95 qualified patients retrieved. There was no difference in age, gender, or oxygenation index between the two groups .α (9.15 ± 1.22) in the study group were comparable with the control group IL-6 (35.27 ± 5.35), IL-10 (48.37 ± 7.25), and TNF-α (9.13 ± 1.25), without significant difference . After treatment, IL-6 (9.25 ± 1.38), IL-10 (16.29 ± 2.64), and TNF-α (3.17 ± 0.45) were significantly lower than the control group IL-6 (21.38 ± 3.42), IL-10 (34.52 ± 5.58), and TNF-α (5.58 ± 0.82). See Before treatment, the levels of IL-6 (35.41 ± 5.26), IL-10 (48.62 ± 7.33), and TNF-P > 0.05). However, the levels of miR-126, miR-184, and MAP1-LC3 in the two groups after treatment were both significantly lower than those before the treatment, and the levels of miR-126, miR-184, and MAP1-LC3 were significantly lower in the study group than those in the control group , miR-184 (12.64 ± 4.17), and MAP1-LC3 (1.07 ± 0.01) of the study group were comparable with the control group of miR-126 (2.05 ± 0.06), miR-184 (12.07 ± 4.24), and MAP1-LC3 (1.05 ± 0.38), and the differences were not statistically significant (ol group .P > 0.05). After treatment, the PEF (67.10 ± 7.28), FRC (90.74 ± 8.63), and TEF25% (54.28 ± 5.27) of the study group were significantly higher than the control group PEF (60.17 ± 8.07), FRC (84.45 ± 9.46), and TEF25% (49.85 ± 5.12) , FRC (64.88 ± 8.48), and TEF25% (42.07 ± 4.83) as the control group PEF (42.07 ± 4.83), FRC (65.27 ± 8.33), and TEF25% (41.44 ± 5.27), and there were no significant differences (P > 0.05). After treatment, the heart rate (82.73 ± 2.54), mean arterial pressure (92.45 ± 0.27), and blood oxygen (98.10 ± 1.01) of the study group were significantly higher than the control group heart rate (65.58 ± 2.67), mean arterial pressure (81.53 ± 1.85), and blood oxygen (95.10 ± 1.20) , mean arterial pressure (80.15 ± 5.42), and blood oxygen (95.15 ± 2.33) of the study group were comparable with the control group heart rate (63.25 ± 1.03), mean arterial pressure (80.23 ± 2.35), and blood oxygen (94.10 ± 2.53), with no significant differences (2/FiO2) is closely related to mortality [Sepsis, an unusual systemic response to common infection or intestinal ischemia/reperfusion, may represent a pattern in the immune system's response to injury . An exceortality . Hemofilortality –18. Howeortality , which wExtracorporeal blood purification is often used to deal with poisoning. Hemofiltration removes solutes from plasma through a membrane induced by a pressure gradient . HVHF isContinuous HVHF can meet the treatment needs of sepsis, but due to the different metabolic and infectious conditions of patients, there is no uniform rate standard. However, it is certain that it is very effective in the treatment of sepsis. In the process of HVHF, the rate of replacement fluid has a great relationship with the removal rate. Early and accurate diagnosis of ARDS would lead to a therapeutic advantage, and the findings of our study will provide valuable clues for the application of traditional Chinese medicine.In conclusion, HVHF has a good clinical effect in improving patients with severe ARDS caused by sepsis and can improve the pulmonary function of patients.


Fatty acids are key components in the structural diversity of lipids and play a strategic role in the functional properties of lipids which determine the integrity of neuronal and glial cell membranes, the generation of lipid signaling mediators, and the chemical reactivity of acyl chains. The present study analyzes using gas chromatography the fatty acid profiles of 13 regions of the human central nervous system in healthy individuals ranging from 40 to 80 years old. The outcomes suggest the existence of general traits in fatty acid composition such as an average chain length of 18 carbon atoms, high monounsaturated fatty acid content, and predominance in polyunsaturated fatty acids of those of series n-6 over series n-3 which are shared by all brain regions regardless of age. Our results also show a general sustained and relatively well-preserved lipid profile throughout the adult lifespan in most studied regions  with minor changes that are region-dependent. In contrast, of particular relevance is the involvement of the inferior temporal cortex and cingulate cortex. It is proposed that during normal human brain aging, the lipid profile is resistant to changes with age in most human brain regions to ensure cell survival and function, but some particular regions involved in specific memory domains are greatly affected.The online version contains supplementary material available at 10.1007/s11357-022-00527-1. Human brain evolution and lipids are closely linked , 2. StruFatty acids are major components of glycerolipids, glycerophospholipids, and sphingolipids. The combination of fatty acids or fatty acids with different head groups (depending on the lipid class) can generate around 10,000 different lipid molecular species . The lenIn this context, it has been suggested that the morphological and functional diversity among neural cells in the human brain is also achieved by the expression of region-specific lipid profiles . In agreolive and upper vermis), midbrain (substantia nigra), diencephalon , subcortical telencephalon , and cortical telencephalon , in healthy individuals without co-morbidities ranging from 40 to 80 years old. The brain areas were selected on the basis of their selective vulnerability to neurodegenerative diseases in aging. Our results show selective brain regional changes in lipid profile with human healthy aging.The present study analyzes the fatty acid profiles of total lipids from the gray matter of 13 different regions of the human central nervous system belonging to the hindbrain  and the approval of the local ethics committee (CEIC/1981).At autopsy, one hemisphere was fixed in 4% buffered formalin for about 3 weeks while the other hemisphere was cut in coronal Sects. 0.5-cm thick; selected areas of the brain were dissected, immediately frozen on metal plates over dry ice, placed in labelled plastic bags, and stored at – 80 °C until use. Procedures were designed to preserve post-mortem material under optimal conditions for morphological and biochemical studies . The posThe neuropathological study, to discriminate healthy brains, was carried out in every case as previously described . BrieflyAdult and middle-aged individuals (< 60 years) had no clinical or neuropathological alterations, whereas old-aged individuals (> 60 years) had no clinical symptoms and neuropathological alteration restricted to stage I of neurofibrillary degeneration. Since the majority of human beings aged 65 years have stages I–II of neurofibrillary tangle pathology , 13, theFollowing initial screening, the present series included 17 cases: 12 males and 5 females, with age ranging from 40 to 80 years. Table 2, and the fatty acyl groups were transesterified by incubation in 2.5 ml of 5% methanolic HCl at 75 °C for 90 min. The resulting fatty acid methyl esters were extracted by adding 1 ml of saturated NaCl solution and 2.5 ml of n-pentane. Finally, the n-pentane phase was separated, evaporated under N2, and redissolved in 75 µl of carbon disulfide. Two microliters was used for GC analysis.Fatty acyl groups of total lipids from gray matter of 13 human brain regions were analyzed as methyl ester derivatives (FAMEs) by gas chromatography (GC) as previously described , 14. FirSeparation was performed with a DBWAX capillary column (30 m × 0.25 mm × 0.25 μm) in a GC System 7890A with a Series Injector 7683B and a FID detector . Sample injection was in the splitless mode. The injection port was maintained at 250 °C, and the detector at 250 °C. The temperature program was 5 min at 145 °C, then 2 °C/min to 245 °C, and finally hold at 245 °C for 10 min, with a post-run at 250 °C for 10 min. So, total run time was 65 min, with a post-run time of 10 min. Identification of fatty acid methyl esters was made by comparison with authentic standards  using a specific software of data analysis for GC from Agilent  and subsequent revision and confirmation by an expert. Results are expressed as mol%.The following fatty acyl indices were also calculated: saturated fatty acids (SFA); unsaturated fatty acids (UFA); ratio SFA/UFA; monounsaturated fatty acids (MUFA); polyunsaturated fatty acids (PUFA) from n-3 and n-6 series (PUFAn-3 and PUFAn-6); and average chain length (ACL) = [ +  +  +  +  + ]/100. The density of double bonds in the membrane was calculated with the double bond index, DBI = [(1 × Σmol% monoenoic) + (2 × Σmol% dienoic) + (3 × Σmol% trienoic) + (4 × Σmol% tetraenoic) + (5 × Σmol% pentaenoic) + (6 × Σmol% hexaenoic)]. Membrane susceptibility to peroxidation was calculated with the peroxidizability index, PI = [(0.025 × Σmol% monoenoic) + (1 × Σmol% dienoic) + (2 × Σmol% trienoic) + (4 × Σmol% tetraenoic) + (6 × Σmol% pentaenoic) + (8 × Σmol% hexaenoic)].Elongase and desaturase activity was estimated from specific product/substrate ratios. For desaturase activity: D9D (n-7) = 16:1n-7/16:0; D9D (n-9) = 18:1n-9/18:0; D5D (n-6) = 20:4n-6/20:3n-6; D6D (n-3) (a) = 18:4n-3/18:3n-3; D6D (n-3) (b) = 24:6n-3/24:5n-3. For elongase activity: Elovl3 (n-9) (a) = 20:1n-9/18:1n-9; Elovl3 (n-9) (b) = 22:1n-9/20:1n-9; Elovl3 (n-9) (c) = 24:1n-9/22:1n-9;Elovl6 = 18:0/16:0; Elovl1-3–7 (a) = 20:0/18:0; Elovl1-3–7 (b) = 22:0/20:0; Elovl1-3–7 (c) = 24:0/22:0; Elovl 5(n-6) = 20:2n-6/18:2n-6; Elovl2-5 (n-6) = 22:4n-6/20:4n-6; Elovl 2–5(n-3) = 22:5n-3/20:5n-3, and Elovl 2(n-3) = 24:5n-3/22:5n-3. Finally, peroxisomal β-oxidation (PβOx) was estimated according to the ratio 22:6n-3/24:6n-3.t-test was used to evaluate differences between age groups. Spearman’s rank correlation was employed to assess possible relations for variables with age. Statistical significance was adjusted for multiple testing by controlling the false discovery rate according to the Benjamini–Hochberg method using a maximum discovery rate of 10%. Graphs were made and t-tests performed using GraphPad prism 8.0.1. Spearman correlation was made using IBM SPSS Statistics (v24.0.0.0). Spearman correlation matrix was constructed using RStudio (v1.3.1073). Functions used were included in the packages corrplot [Hmisc [p values inferior to 0.05 were considered statistically significant.Data were expressed as mean values ± SEM. Student’s corrplot  and Hmist [Hmisc . p valueThe changes in brain fatty acid profile along the aging process were assessed by analyzing 25 different fatty acid species across 13 different brain regions, including the olive (medulla oblongata) and vermis (cerebellum) (hindbrain); substantia nigra (midbrain); thalamus ; hippocampus, caudate, and putamen ; and occipital, parietal, temporal, entorhinal, frontal, and cingulate cortex . Results revealed that 16:0, 18:0, and 18:1n-9 are the most abundant fatty acids in human healthy brain, in both the middle-aged and the elderly, accounting for approximately 60% of global fatty acid composition  and increase in 22:5n-3  and 24:6n-3 , fatty acids with a very low abundance, and no involvement in general indexes in the elderly group compared to the middle-aged group, whilst vermis only showed an increase in 20:0  in the elderly group, without any additional change. In the midbrain, and in a similar way to hindbrain, substantia nigra only showed an increase in 16:1n-7 , and the very minor fatty acids 18:4n-3  and 24:0 , as well as SFA content , and a decrease in ACL  and UFA .Comparison of middle-aged and elderly groups throughout the different brain regions analyzed verified the existence of minor changes Table . Thus, ithalamus showed a decrease in 22:4n-6  content and ACL , and an increase in 24:5n-3  content in the elderly group compared to the middle-aged group. In subcortical telencephalon, the three analyzed regions, hippocampus, caudate, and putamen, also showed minor changes in the elderly group. Thus, in hippocampus, we only found a decrease in the relative abundance of fatty acids 22:1n-9  and 22:4n-6 ; in caudate nucleus a decrease in 18:3n-3 , 24:0 , and 24:6n-3 , and an increase in the content of 20:0  and 20:4n-6 ; and in the putamen nucleus, a decrease in 22:4n-6 , 22:5n-6 , and PUFAn-6  contents, as well as ACL .In diencephalon, occipital cortex (areas 17–18), fatty acid composition analysis revealed a slight increase in the ACL  in the elderly group compared to the middle-aged group; in parietal cortex (area 7), a decrease in 14:0  content, and increase in PUFAn-3  and DBI  was observed; in temporal cortex , a decrease in 22:4n-6 , 22:5n-6 , 24:5n-3 , 24:6n-3 , and PUFAn-6 , and an increase in 20:0  and estimation of the peroxisomal β-oxidation activity  was detected; in entorhinal cortex, the only observed change was a decrease in PUFAn-6 content ; in frontal cortex (area 8), no change was verified; and finally, in cingulate cortex (area 24), only a slight increase in 20:0  was revealed.Finally, six regions from human cerebral cortex  were analyzed, again showing minor changes in the elderly group. Thus, in p values when comparing the two groups of cases is shown in Table Because of the large number of tests, adjustment for multiple comparisons was assessed using the Benjamini–Hochberg false discovery rate (FDR) analysis. Since some of the observed changes in the elderly group may be due to alterations in the activity of the enzymes involved in the fatty acid biosynthesis, elongase and desaturase activity was estimated from specific product/substrate ratios. The outcomes confirm the existence of minor changes induced by aging across the different brain regions (Supplementary Table p < 0.01) and (b) (p < 0.05) estimated activity in vermis was observed. In the midbrain, substantia nigra showed an increased estimated D6D (a) (p < 0.05), Elovl1-3–7 (c) (p < 0.001), and Elovl2 activity (p < 0.05), and decrease in D6D (b) activity (p < 0.05). In the diencephalon, thalamus D6D (b) and Elovl2-5 (n-6) estimated activity was decreased . In the subcortical telencephalon, a reduced estimated activity of Elovl1-3–7 (b) and (c) , Elovl3 (a) (p < 0.05), and Elovl2-5(n-6) (p < 0.05), and very slight increase of Elovl1-3–7 (a) (p < 0.05) activity were found in the caudate nucleus, whereas in the putamen nucleus Elovl1-3–7 (b) activity was decreased (p < 0.05) along with an enhanced Elovl1-3–7 (c) and Elovl2 activity (both p < 0.05). Finally, in the six regions of the human cerebral cortex , little changes were observed and included a very small increase in Elovl1-3–7 (a) activity (p < 0.05) in the occipital cortex, reduced D6D (b) (p < 0.05) and Elovl2 (p < 0.05) along with an enhanced Elovl6 (p < 0.05) and Elovl1-3–7 (a) (p < 0.05) estimated activity in the temporal cortex, and a slight increase of Elovl1-3–7 (a) (p < 0.05) in cingulate cortex. No changes in the estimated enzymatic activity were detected in olive (hindbrain), hippocampus , and parietal, entorhinal, and frontal cortex . These results suggest a global increase of the Elovl1-3–7 (a) along with a reduced Elovl1-3–7 (b) and D6D (b) estimated activities in the elderly.The changes observed on the elderly compared with the middle-aged group were region-dependent. Specifically, in the hindbrain, a reduced Elovl1-3–7 (a)  and (c) and elovl2 in putamen were sustained following multiple comparison adjustment.Because of the large number of tests, adjustment for multiple comparisons was assessed using the Benjamini–Hochberg false discovery rate (FDR) analysis. An additional approach was used to learn about the lipid composition changes as a function of age, as a continuous variable instead of dichotomizing the data into a middle-aged and an elderly cohort. To this end, the existence of correlations between fatty acid composition and age was evaluated by applying a Spearman correlation test. Results are presented in Supplementary Table olive and vermis  content and DBI (p = 0.023) with age  was added , and in the putamen, an increase with age in the content of 16: 0 (p = 0.022) and 24:5n-3 (p = 0.006) was additionally observed , 22:4n-6 (p = 0.007), 22:5n-6 (p = 0.049), and 24:1n-9 (p = 0.033) ; in parietal cortex, decrease in content of 14:0 (p = 0.027), and increase in content of 22:6n-3 (p = 0.007) and, concomitantly, ACL (p = 0.006), PUFA (p = 0.015), and PI (p = 0.019); in entorhinal cortex, the increase in 20:0 (p = 0.017); and in frontal cortex, the increase in 20:0 (p = 0.023), and the decrease in 22:5n-6 (p = 0.018)  detected in the comparison between middle-age vs elderly individuals, the following new correlations should be added: decreased content with age of 16:0 (p = 0.008), 20:4n-6 (p = 0.025), 22:5n-6 (p = 0.018), SFA (p = 0.008), PUFAn-6 (p = 0.003), and ratio SFA/UFA (p = 0.008); and increased content with age of 16:1n-7 (p = 0.024), 18:1n-9 (p = 0.026), 20:1n-9 (p = 0.04), 22:0 (p = 0.023), 24:0 (p = 0.021), 24:1n-9 (p = 0.018), 24:6n-3 (p = 0.019), ACL (p = 0.009), UFA (p = 0.008), and MUFA (p = 0.027). Globally, these changes may be attributed to enhanced metabolic activity of the elongases and desaturases involved in the biosynthesis of SFA and MUFA from 16:0 , 22:4n-6 (p = 0.002), 22:5n-6 (p = 0.006), 24:5n-3 (p = 0.024), 24:6n-3 (p = 0.011), ACL (p = 0.04), PUFA (p = 0.022), PUFAn-6 (p = 0.001), DBI (p = 0.033), and PI (p = 0.047) was observed with age; while 18:1n-9 (p = 0.001), MUFA (p = 0.02), and peroxisomal β-oxidation activity (p = 0.001) showed an increase with age. All these changes are suggestive of alterations with age in the PUFAn-6 biosynthesis pathway, as well as at the peroxisomal level ; in vermis for 20:0 (p = 0.035); in thalamus for 22:4n-6 (p = 0.001) and ACL (p = 0.001); in putamen for 22:4n-6 (p = 0.001) and ACL (p = 0.001); in temporal inferior cortex for 18:1n-9 (p = 0.018), 22:4n-6 (p = 0.023) and PUFAn-6 (p = 0.018), and in cingulate cortex for 16:0 (p = 0.045), 20:0 (p = 0.045), ACL (p = 0.045), SFA (p = 0.045), UFA (p = 0.045), PUFAn-6 (p = 0.045), and ratio SFA/UFA (p = 0.045).Adjustment for multiple correlations was assessed using the Benjamini–Hochberg false discovery rate (FDR) analysis. Finally, we have developed a series of correlation matrixes for integrative indexes in order to evaluate the existence of regional relationships Fig. . The resThe human brain aging process induces changes at all levels of biological organization, although with a heterogeneous interregional impact, which demands adaptive responses in order to preserve the composition and function within physiological limits. The lipid bilayer that composes neuronal and glial cell membranes is not on the sidelines; consequently, the longer the optimal membrane lipid profile is sustained, the better neural cell function and survival.The first evidence of changes in the lipid profile in the human brain during aging revealed, analyzing the whole brain, that there is a slow and progressive decrease with age in the total lipid content from the second-third decade of life –19. LateThe fatty acid profile and its changes with aging have also been the subject of study in various works. In these studies, different regions of the human cerebral cortex such as frontal cortex (area 8) , 30, preInferior temporal cortex area 20 and cingulate gyrus area 24 are the two brain regions most affected by aging, showing the most extensive changes in fatty acid profiles. Notably, the two regions share some changes, while others are region specific, highlighting the increased content in MUFAs, ascribed to the 18:1n-9 acyl chain, and decreased content of PUFAn-6, basically due to a decreased content of 20:4n-6 and 22:5n-6. While the 18:1n-9 increase could be attributed to an increase in D9D activity, the 20:4n-6 and 22:5n-6 decreases do not appear to depend on changes in the desaturase and elongase activity of their biosynthesis pathway, so the alteration in their content should be attributed to potential increases in its consumption , since tIn contrast to the compositional sustainability with aging that characterizes most brain areas, in pathological conditions such as Alzheimer’s disease (AD) a marked change in temporal trajectory of the lipid profile is observed. Effectively, the involvement of lipid alterations in AD brains has been well-established in the last years, in particular with reference to PUFA and cholesterol contents (reviewed in –39). AltAnother interesting observation of the present study is that some of the observed changes in fatty acid profile with age showed a breakpoint after the age of 50. This finding is in line with additional changes such as transcriptional defects related to mitochondrial electron transport chain and signaling pathways involved in neuronal survival, decreased concentration of the main lipid classes, and increased oxidation-derived protein damage that also take place at this age , 41–43. Globally, age-associated changes in terms of individual fatty acid content in the brain are heterogeneous. Thus, forebrain appears to be the region most affected by the aging process. Few changes were found in substantia nigra in the midbrain, whereas hindbrain global fatty acid composition appeared to be unaffected by the aging process. Our findings also suggest that major adult human brain fatty acids undergo slight but progressive and significant changes in their abundance during the aging process, with some changes showing a breakpoint after the age of 50. However, the individual contribution of these fatty acid patterns to the aging process is as yet unknown. Therefore, goals of future research are to define which types of lipid molecular species change with age in the different human brain regions, to extend the lipidomics analysis to additional brain regions not studied, to analyze lipid patterns according to neural cell-type specificity, and how they relate both to the function of the area and to the dysfunction leading to neuropathology. Indeed, it is not yet known whether the changes in fatty acids represent neutral changes with age, changes causing physiological aspects of aging, or adaptative responses to damaging agents. In any case, the findings described here suggest that fatty acids and their metabolism are closely linked to human brain aging.Supplementary file1 (DOCX 86 KB)Below is the link to the electronic supplementary material.


Gm114 deficiency induces a stronger inflammatory response, more severe acute colitis and lower survival rate in mice compared with control mice. Collectively, our study not only identifies KIZ/GM114 as a negative regulator to balance the NF-κB signaling, but it also implies a new strategy for limiting excessive inflammatory response.NF-κB signaling is a pivotal regulator of the inflammatory response and it must be tightly controlled to avoid an excessive inflammatory response that may lead to human chronic inflammatory and autoimmune diseases. Thus, how NF-κB signaling is precisely controlled is a long-standing question in the field. TRAF family proteins function as key adaptors to mediate NF-κB signaling induced by various receptors. Here, we characterize KIZ/GM114 as a negative regulator balancing the NF-κB signaling. Mechanistically, KIZ/GM114 binds TRAF6/2 by targeting the TRAF domains to antagonize the TRAF6-IRAK1 association or the TRAF2-TRADD association, consequently reducing the IL-1β/LPS/TNFα-induced NF-κB activation. Importantly, upon dextran sulfate sodium treatment,  Nuclear factor-κB (NF-κB) signaling plays a critical role in regulating the inflammatory response by modulating the expression of inflammatory proteins and proinflammatory cytokines . VariousDrosophila Bam forms a complex with Otu by targeting dTRAF6 for the cleavage of its K63-linked ubiquitin chains. Thus, Otu/Bam regulates immune deficiency (IMD) signaling to maintain gut immune homeostasis, thereby controlling the fly lifespan  compared with wild-type mice because of higher inflammatory responses.Tumor necrosis factor receptor–associated factor (TRAF) proteins function as key signaling molecules to mediate a variety of receptor-signaling pathways that involving in immune response, development and diseases . Typicallifespan . Of notetivation . Mouse Gtivation . In thisDrosophila Bam played a role in regulating IMD signaling. Considering that GM114 is a putative mouse homolog of Drosophila Bam, we investigated whether GM114 and its human homolog KIZ also contributed to regulating the NF-κB signaling pathway in mammals. First, we overexpressed KIZ or the empty vector in C6 cells that ectopically express IL-1R and then stimulated the cells with IL-1β, followed by quantitative PCR (qPCR) and immunoblotting. qPCR showed that KIZ overexpression significantly reduced the transcriptional levels of IL-1β-induced NF-κB downstream genes that included IL8 and TNFα  from 13.5-day-old embryos of Gm114+/+ and Gm114−/− mice by breeding heterozygous mutants and then stimulated the cells with IL-1β. As shown in Il6 and Il1β were significantly enhanced in Gm114−/− MEFs compared with the WT controls in response to IL-1β stimulation. Consistently, immunoblotting showed that Gm114 depletion increased the levels of phosphorylated IKKα/β and p65 induced by IL-1β  assays to further identify the target proteins of KIZ by screening KIZ-associated proteins in the NF-κB signaling pathway. HEK293T cells were co-transfected with KIZ and the important components of the NF-κB signaling pathway, which included IRAK1, TRAF6, TAK1, TAB1, TAB2, IKKα, IKKβ, and p65. Co-IP indicated that KIZ strongly associated with TRAF6 and TAK1, but not other proteins . The str not GFP . These rIL8 and TNFα mRNAs induced by IL-1β in TRAF6-knockdown cells , which is further divided into a RING finger domain and a Zn Finger domain, and a C-terminal TRAF domain (TRAF6-C), which facilitates TRAF protein oligomerization and interactions with other signaling proteins . Thus, wNext, we determined whether the interaction between KIZ and TRAF6 is required for the function of KIZ in regulating NF-κB signaling. Reporter assays showed that KIZ-N and KIZ-C truncated variants had an attenuated function in inhibiting the NF-κB activity induced by TRAF6 compared with full length KIZ , whereasNext, we investigated how KIZ modulated TNFα-induced NF-κB signaling. Considering that TRAF2 plays an important role in the activation of NF-κB induced by TNFα and shares similar structures to TRAF6, we examined whether KIZ interacts with TRAF2. Co-IP indicated that KIZ had a strong association with TRAF2 . Next, tIL8 and TNFα induced by TNFα in TRAF2 knockdown cells  and a C-terminal TRAF domain (TRAF2-C) . Therefovia targeting TRAF6. Because TRAF6 functions as E3 ligase to catalyze K63-linked polyubiquitination chains, subsequently activates the TAK1 and IKK complexes, we examined whether KIZ regulated the synthesis of K63-linked ubiquitination chains catalyzed by TRAF6. In vitro ubiquitination assays showed that KIZ had no effects on the synthesis of K63-linked ubiquitination chains catalyzed by TRAF6 , which is a widely employed model of inflammatory bowel disease with many similar features to human inflammatory bowel diseases .Gm114+/+ and Gm114−/− MEFs were generated from 13.5-day-old embryos and maintained in complete DMEM containing 1 mM sodium pyruvate (Gibco), 10 μM L-glutamine, 10 μM β-mercaptoethanol, and 1% nonessential amino acids (Gibco). Bone marrow cells were isolated from 8-weeks-old Gm114+/+ and Gm114−/− mice and cultured with IMDM (Gibco) medium containing conditioned media from L929 cell culture, 10% fetal bovine serum, 1 mM sodium pyruvate and 1% streptomycin and penicillin for 5 days to generate BM-derived macrophages (BMDM).HEK293T, HeLa, RAW264.7 cells and U2OS cells were cultured with high-glucose DMEM (Gibco) medium containing 10% heat-inactivated fetal bovine serum (Invitrogen) and 1% streptomycin and penicillin (Gibco). THP-1 cells were cultured in RPMI-1640 containing 10% fetal bovine serum, 1% streptomycin and penicillin, 10 mM HEPES (pH7.0), and 10 µM β-mercaptoethanol. 6-KIZ (residues 563-674) and His6-GM114 (residues 149-294) produced in E. coli, respectively.Rabbit anti-p-p65 , anti-p-TAK1 , anti-TAK1 (5206), anti-p-IKKα/β , anti-IKKβ (8943), anti-IRAK1 (4504), anti-IκBα (9242) and mouse anti-p-IκBα  antibodies were purchased from Cell Signaling Technology. Rabbit anti-TRAF2 (SC-876) and mouse anti-p65 (SC-8008), anti-ubiquitin (SC-8017) antibodies were purchased from Santa Cruz Biotechnology. Rabbit anti-TRAF6 (ab40675) was purchased from Abcam. Other antibodies used were as follows: Rabbit anti-Flag (Sigma); rabbit anti-HA (MBL); rabbit anti-Myc (MBL); mouse anti-GAPDH  and mouse anti-αTubulin . The antibodies against KIZ and GM114 were generated by immunizing mice with the recombinant proteins HisHuman full length KIZ and mouse full length GM114 were cloned into pEF vectors. KIZ truncated variants were cloned into pEF-HA vectors. The plasmids encoding MyD88, TRAF6, TAK1, TAB1, TAB2, IKKα, IKKβ, p65, Renilla reporter, and NF-κB-Luc reporter have been described previously E. .shKIZ-1: GTCTGATACATGCAGAGTTAA;shKIZ-2: CAAGGGAACAAGAAGTTTCAA;shTRAF6: GCCACGGGAAATATGTAATAT;shTRAF2: CTCGGGCATGACAGGCAGAAA.Full length cDNA that encoded KIZ or Gm114 was amplified and inserted into a pCDH-CMV-Puro vector. Lentivirus particles for KIZ or GM114 overexpression were produced by co-transfecting the pCDH-CMV-Puro-KIZ or GM114 construct into HEK293T cells with the packaging plasmids pMD2.G and pAS-MAX. To generate knockdown cells, we employed pLKO.1-puro-based lentiviruses that expressed specific short hairpin RNAs (shRNAs) against KIZ, TRAF6 or TRAF2. Cells were infected with shRNA lentiviruses that targeted the indicated gene or a control vector (pLKO.1). The knockdown efficiency was determined by qPCR. The shRNA sequences against the KIZ, TRAF6 and TRAF2 were as follows (5′–3′):KIZ were inserted into the pX330-GFP-U6-Chimeric_BB-CBh-hSpCas9 vector. HEK293 C6 cells were co-transfected with these two expression plasmids. Twenty-four hours later, single cells that expressed GFP were isolated by fluorescence-activated cell sorting. Knockout cells were verified by immunoblotting. The sgRNA sequences were (5′→3′):KIZ-gRNA#1: CGGCCCATAAAGATTGTTGC TGG;KIZ-gRNA#2: ACTTAATCTTTCCCGTAACG GGG.Two sgRNAs that targeted different DNA regions of HEK293T cells were transfected with various expression plasmids along with NF-κB-Luc (10 ng/well) and Renilla reporter plasmid (25 ng/well) in a 24-well plate using polyethylenimine. Twenty-four hours post-transfection, the cells were lysed using passive lysis buffer (Promega) for luciferase activity, followed by immunoblotting, and transfection efficiency was normalized to Renilla activity.in vivo Co-IP, cells were lysed in lysis buffer  with a fresh protease inhibitor cocktail (Roche). Clarified supernatants were incubated with anti-Flag agarose beads (Sigma) or anti-HA magnetic beads (Pierce) for 4 h at 4°C. Immunoprecipitated complexes were washed three times with lysis buffer that contained 300 mM NaCl and then subjected to immunoblotting with the indicated antibodies.For in vitro pull-down experiments, recombinant GFP-TRAF6 protein, GFP, and His-KIZ were purified from E. coli. His-KIZ protein was incubated with GFP or GFP-TRAF6 at 4°C for 3 h and then incubated with anti-GFP agarose beads at 4°C for 2 h, washed three times with washing buffer  and subjected to immunoblotting.For E. coli. For in vitro ubiquitination assays, recombinant E1, Ubc13/Uev2, ubiquitin, and His-TRAF6 were mixed in ATP buffer  in the presence or absence of His-KIZ recombinant protein. The reaction mixture was incubated for 1 h at 30°C and the reaction was terminated by addition of denaturing sample buffer, followed by heating at 95°C for 5 min. The samples were resolved on 6–18% or 10% SDS-PAGE gels, followed by immunoblotting.Recombinant E1, Ubc13/Uev2, and ubiquitin proteins were kindly provided by Dr Zongping Xia (Zhengzhou University). His-TRAF6 and His-KIZ recombinant proteins were purified from Total RNA was extracted using TRIzol reagent (Invitrogen) in accordance with the manufacturer’s instructions. cDNA was synthesized using a HiScript III 1st Strand cDNA Synthesis Kit (Vazyme). Quantitative PCR was performed in triplicate using SYBR Green Master Mix (Thermo Fisher) on a Bio-Rad CFX connect system. Relative levels of mRNA were normalized to the levels of GAPDH in each sample. Data shown are relative mRNA abundance compared with control groups.KIZ-S GGTGTTTCAGATCATCTTGCTC;hKIZ-AS CCTCTATTCCATCTTCTCCCTC;hIL6-S TCCAGAACAGATTTGAGAGTAGTG;hIL6-AS GCATTTGTGGTTGGGTCAGG;hIL8-S ATAAAGACATACTCCAAACCTTTCCAC;hIL8-AS AAGCTTTACAATAATTTCTGTGTTGGC;hTNFα-S CTGCCCCAATCCCTTTATT;hTNFα-AS CCCAATTCTCTTTTTGAGCC;hTRAF6-S TTTGCTCTTATGGATTGTCCCC;hTRAF6-AS CATTGATGCAGCACAGTTGTC;hTRAF2-S TCCCTGGAGTTGCTACAGC;hTRAF2-AS AGGCGGAGCACAGGTACTT;hIFIT1-S TACCTGGACAAGGTGGAGAA;hIFIT1-AS GTGAGGACATGTTGGCTAGA;hGAPDH-S ATGACATCAAGAAGGTGGTG;hGAPDH-AS CATACCAGGAAATGAGCTTG;hIl6-S TCGGAGGCTTAATTACACATGTTCT;mIl6-AS TGCCATTGCACAACTCTTTTCT;mIl-1β-S AAAGCCTCGTGCTGTCGGACC;mIl-1β-AS CAGGGTGGGTGTGCCGTCTT;mTnfα-S TCCCCAAAGGGATGAGAAGTT;mTnfα-AS GTTTGCTACGACGTGGGCTAC;mGapdh-S AACTTTGGCATTGTGGAAGG;mGapdh-AS ACACATTGGGGGTAGGAACA.mThe primers used for qPCR were as follows (5′-3′):Mice were administered 2.5% (w/v) DSS  in drinking water for a period of 7 days, followed by normal drinking water for 7 days or 5% (w/v) DSS for 5 days, followed by normal drinking water. The survival rate and weight loss of the mice were monitored for 14 consecutive days from the first day of DSS exposure to the day of death. Disease activity index (DAI) scores were evaluated on day 5 after DSS treatment on the basis of weight loss, stool consistency, and the degree of rectum bleeding . Sera wet-test (GraphPad Prism 8.0). For all tests, p-values of <0.05 were considered statistically significant.The log-rank (Mantel–Cox) test was used for survival rate analysis. Other statistical analyses are shown as mean ± SD. Statistical analysis was carried out using the two-tailed Student’s


Curiously, within the resulting co-crystal (6I2Cl4C)·(TPCB), the photoproduct accepts only two halogen bonds between neighbouring 4-pyridyl rings and as a result behaves as a bent two-connected node rather than the expected four-connected centre. In addition, the photoproduct, TPCB, is also found to engage in C—H⋯N hydrogen bonds, forming an extended zigzag chain.The formation and crystal structure of a zigzag network held together by I⋯N halogen bonds is reported. In particular, the halogen-bond donor is 1,3-diiodoperchlorobenzene ( Unexpectedly, the TPCB molecule is found to accept only two I⋯N halogen bonds, between neighbouring 4-pyridyl rings, which makes the photoproduct act as a bent two-connected node rather than a four-connected node as seen in the square network topology with the sulfate anion ·(TPCB) crystallize in the centrosymmetric monoclinic space group P21/c. The asymmetric unit contains a full molecule of both 6I2Cl4C and TPCB , 96.05 (7), 96.37 (7) and 100.50 (7)°. These bond angles were measured from the centroids of the cyclobutane and the pyridine rings. As expected, the halogen-bond donor 6I2Cl4C forms two crystallographically unique I⋯N halogen bonds with TPCB. The halogen-bond distances between I1⋯N4 and I2⋯N3i have values of 2.757 (4) and 2.909 (4) Å along with bond angles for C1—I1⋯N4 and C3—I2⋯N3i of 176.58 (15) and 172.73 (16)°, respectively . Surprisingly, within (6I2Cl4C)·(TPCB) only two adjacent 4-pyridyl rings are accepting these I⋯N halogen bonds. As a consequence of the observed formula and the lower than expected number of halogen bonds, TPCB behaves as a bent two-connecting node, resulting in a zigzag topology ·(TPCB) is 20.51 (2) Å measured from the centroids of two nearest cyclobutane rings within the chain. Even though the I atoms on 6I2Cl4C are found in the meta positions, rather than the para position, this halogen-bond donor acts as a nearly linear linker within (6I2Cl4C)·(TPCB)  Fig. 2.3.6I2Cl4C)·(TPCB), the photoproduct TPCB is found to engage in a C—H⋯N hydrogen bond, resulting in a mono-periodic zigzag chain  and used as received. In addition, resorcinol (res), trans-1,2-bis(pyridin-4-yl)ethylene (BPE), concentrated sulfuric acid, and sodium hydroxide pellets were also purchased from Sigma-Aldrich and were used without additional purification. The [2 + 2] cycloaddition reaction was conducted in an ACE Glass photochemistry cabinet using UV-radiation from a 450 W medium-pressure mercury lamp. The occurrence of both the [2 + 2] cycloaddition reaction along with the acid-catalysed isomerization reaction were confirmed by using 1H Nuclear Magnetic Resonance Spectroscopy on a Bruker Avance 400 MHz spectrometer with dimethyl sulfoxide (DMSO-d6) as the solvent. The halogen-bond donor 1,3-diiodoperchlorobenzene (6I2Cl4C) was synthesized utilizing a previously published method cyclobutane (TPCB) was achieved by using a previously published approach ·2(BPE) undergoes a [2 + 2] cycloaddition reaction to yield rctt-tetrakis(pyridin-4-yl)cyclobutane as previously reported .6I2Cl4C)·(TPCB) was achieved by dissolving 64.0 mg of 6I2Cl4C in 2.0 mL of toluene and then combined with a 2.0 mL ethanol solution containing 25.0 mg of TPCB . Within three days, single crystals suitable for X-ray diffraction were formed upon loss of some of the solvent by slow evaporation.The formation of  I. DOI: 10.1107/S2056989023001408/zl5042Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989023001408/zl5042sup3.docxNMR spectrum. DOI: Click here for additional data file.10.1107/S2056989023001408/zl5042Isup4.cmlSupporting information file. DOI: 2236158CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


Three independent unit-cell molecules are folded along their Te⋯Te axes, with an average angle φ = 57.9°. C—Te—C angles range from 91.48 (6) to 93.80 (6)°. Intermolecular N⋯Te bonding interactions between tellurium atoms of the central ring and the pyrazine N atoms of adjacent molecules result in a supramolecular helix motif.The title compound, C b:5,6-b′]dipyrazine represents the first reported chalcogenadipyrazine containing a heavy chalcogens The asymmetric unit consists of three molecules. In contrast to its sulfur analog, which is planar Ditellurino[2,3- al. 1994 Cryst. S A sulfur analog of the title compound has been structurally characterized  to 93.80 (6)°, similar to those of 95.3 and 95.9°, respectively, previously reported for telluranthrene ,  = , ,  and : PXTELL , sodium hydride  and dry N-methyl-2-pyrrolidone (12 ml). The mixture was purged with nitrogen, placed in a Wood’s metal bath and heated to 453 K with mechanical stirring for two hours. 2,3-Dichloropyrazine  was then added, followed by continued stirring at 453 K. The mixture was allowed to cool and diluted with water (100 ml). Solids were collected by filtration and dried. They were subsequently extracted with 2 × 10 ml of chloroform. The combined extracts were chromatographed on a 1.5 × 10 cm column  using chloroform as mobile phase, followed by chloroform: acetonitrile (10:1 v/v). A yellow band eluted first and was identified as bis(pyrazin-2-yl)tellurium by mass spectrometry. This was followed by a blue band, identified as bis(3-chloropyrazin-2-yl)ditellurium. The following yellow band contained the title compound. Crystallization from chloroform solution furnished yellow crystals, m.p. 413–415 K, yield 46 mg (2.2%).Properties:1H NMR : 8.31 . 13C NMR : 1443.46, 154.32. The compound slowly oxidizes when exposed to air in solution. A sample suitable for X-ray crystallography was obtained by evaporation of a solution in chloroform.HKL5 file prepared by ROTAX  I. DOI: 10.1107/S2414314622006228/hb4407Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2414314622006228/hb4407Isup3.cmlSupporting information file. DOI: 2179053CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


The angles between the mean planes of the phenyl and pyridyl fragments within the individual ligands range from 3.5 (2) to 11.4 (2)° to deviate slightly from coplanarity.The title cyclometalated distorted octahedral iridium complex, [Ir(C The photophysical properties of cyclometalated iridium(III) complexes have been studied extensively in diverse applications such as cell imaging and OLEDs ](PF6), the nitrogen atoms of the bipyOMe ligand are oriented trans to the carbon atoms of the dfppy ligands phenyl](hydrogen pyridin-2-yl-phosphonato)iridium(III) [Ir—N = 2.153 (4) Å; Zeng et al., 2019et al., 2017et al., 2012trans-interactions compared to other potential isomers that would orient only one of the bipyOMe nitrogen atoms across from a strong trans-donor carbon atom, or that would have both strong trans-donor carbon atoms opposing one another .The title compound, [Ir(dfppy)ds Fig. 1. The Ir—trans-effect, an angular distortion occurs from the chelating ligands, with cis-angles about iridium ranging from 76.39 (10) to 101.08 (12)°, and trans-angles about iridium ranging from 172.49 (12) to 177.11 (12)°. The ligands themselves deviate slightly from coplanarity, with mean plane to mean plane angles between the phenyl and pyridyl fragments within the individual ligands ranging from 3.5 (2) to 11.4 (2)°. The methyl groups of the bipyOMe ligands both fold inward. Neighboring complexes form dimers − anions  and 4,4′-dimethoxy-2,2′-bipyridine  were combined in ethylene glycol (5 ml). The resulting yellow–green heterogenous mixture was heated under N2 to 150°C while stirring. After 20 h, the resulting yellow homogenous solution was allowed to cool to room temperature and 10 ml of NH4PF6 (sat. aq.) were added. The yellow precipitate that formed was collected by vacuum filtration, washed with H2O (3 × 10 ml), Et2O (3 ×10 ml), and dried in vacuo to give a yellow powder . Yellow needle-like crystals suitable for X-ray diffraction were obtained by vapor–vapor diffusion from a solution of hexanes and dichloromethane. 1H NMR  δ 8.48 , 8.28 , 8.03 , 7.75 , 7.65 , 7.28 , 6.97 , 5.61 , 4.00 .[Ir(dfppy)Crystal data, data collection, and structure refinement details are summzarized in Table 210.1107/S2414314622008306/zl4051sup1.cifCrystal structure: contains datablock(s) I. DOI: 10.1107/S2414314622008306/zl4051Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2414314622008306/zl4051Isup3.cdxSupporting information file. DOI: 2202472CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


The synthesis, crystal structure, absolute configuration, spectroscopic and spectrometric details of topiramate azidosulfate, a precursor to the anti-convulsant drug topiramate, are presented. O-(1-methylethylidene)-β-d-fructopyranose azidosulfate], C12H19N3O8S, an intermediate in the synthesis of the anti-convulsant drug topiramate, are described. Topiramate azidosulfate (I) finds use as a reference impurity standard for topiramate. A modified synthesis and some spectroscopic details are also presented.The low (90 K) and room (298 K) temperature crystal structures of topiramate azidosulfate [systematic name 2,3:4,5-bis- The points of fusion, atoms C1, C2, C3, C4  and by their Cremer–Pople  each bear two methyl groups. The azidosulfonate group attaches to atom C1 via a methylene linker, with the position of the azide relative to the fused-ring system determined by torsions about four bonds , as summarized in Table 2Supramolecular features). As there are no substantive differences, unless stated otherwise, numerical quantities quoted in the discussion pertain to the low-temperature structure.The molecule of C4 Fig. 1, are conople 1975 ring-pucople 1975. The dis3.I. The ‘HTAB’ instruction in SHELXL flags four ‘potential hydrogen bonds’  x − 1, y, z], the latter being the stronger of the two. During structure analysis, the question arose of whether these contacts would be structurally significant, owing to the possibility of rapid methyl-group rotation at room temperature , but these are marginally greater than the sum of van der Waals radii of Bondi  attached to the equivalent of C1 in I returned 26 hits (21 excluding duplicates). A search using the keyword ‘topiramate’ gave only three hits, all being the structure of topiramate itself (with NH2 in place of N3 in I): SEQKAA  is present as entry ZARCEC  form a tri-periodic hydrogen-bonded supramolecular assembly, while ZARCEC forms C(4) chains  synthesis of 2,3:4,5 bis-O-(1-methylethylidene)-β-d-fructopyranose, (2) synthesis of 2,3:4,5-bis-O-(1-methylethylidene)-1-chlorosulfate-β-d-fructopyranose, and (3) synthesis of topiramate azidosulfate (I), as depicted in Fig. 6I were obtained by crystallization from dichloromethane (m.p.: 358–359 K). Some spectroscopic details are as follows:Topiramate azidosulfate was synthesized using a modification of procedures found in the literature (Maryanoff −1): 2157 (N=N=N stretching); 1392 (S=O stretching); 1167 and 1081 (C—O stretching); 1H NMR: CDCl3 : 1.355 ; 1.422 ; 1.489 ; 1.566 ; 3.783–3.817 and 3.908–3.945 ; 4.246–4.268 ; 4.306–4.332 ; 4.398–4.424 ; 4.622–4.649 . MS m/z: 364.03 (M—H)+IR (cm6.RCH3), 0.99 Å (R2CH2) and 1.00 Å (R3CH). Uiso(H) parameters were set to values of either 1.2Ueq or 1.5Ueq (RCH3 only) of the attached atom. The absolute configuration was determined unambiguously from the anomalous scattering by sulfur using established methods  global, I-90K, I-298K. DOI: 2204998, 2204997CCDC references:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


The overall error values for van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10−2 in PEG-400 at 318.2 K, however the least one was 1.97 × 10−7 in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10−2) > THP (1.70 × 10−2) > 2-BuOH (1.38 × 10−2) > 1-BuOH (1.37 × 10−2) > IPA (1.10 × 10−2) > EtOH (8.37 × 10−3) > EA (8.31 × 10−3) > DMSO (7.35 × 10−3) > MeOH (3.26 × 10−3) > PG (1.88 × 10−3) > EG (1.31 × 10−3) > water (1.14 × 10−6) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was “endothermic and entropy-driven” in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility.This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including “water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 298.2–318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with “van’t Hoff, Buchowski-Ksiazczak  Febuxostat (FBX)  class II drug with poor solubility in aqueous media and high permeability . Its solOther researched mono solvents such as isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO) have not had their solubility and other physicochemical data published. As a result, new solubility and physicochemical data for FBX in various mono solvents, including water, MeOH, EtOH, IPA, 1-BuOH, 2-BuOH, EG, PG, PEG-400, THP, EA, and DMSO at 298.2–318.2 K and 101.1 kPa, are reported in this study. “Apparent thermodynamic analysis” was carried out to evaluate the dissolution behavior of FBX in various mono solvents. The solubility and physicochemical data of FBX obtained in this research could be used in “purification, recrystallization, drug discovery, pre-formulation studies, and formulation development” of FBX.The FBX (form H) standard drug was procured from “E-Merck ”. EG, PG, PEG-400, EA, and DMSO were procured from “Sigma Aldrich ”. MeOH, EtOH, IPA, 1-BuOH, and 2-BuOH were obtained from “E-Merck ”. The Milli-Q unit provided purified water. The details about each material are summarized in 18 column” was used for the chromatographic analysis of FBX. The binary mixture of EtOH and EA  was used as the greener solvent system under the flow rate of 1.0 mL min−1. Prior to use, the greener solvent combination was freshly produced, filtered through nylon filter paper with a pore size of 0.45 µm, and degassed. The injection volume was set at 20 µL. The FBX calibration curve was created by plotting the FBX concentrations against the measured HPLC response. In the range of 1–100 µg g−1, the calibration plot of FBX was linear, with a determination coefficient (R2) of 0.9979. The regression line equation for FBX was y = 46,266x + 14,848; where x and y represent the FBX concentration and observed HPLC response, respectively.A validated HPLC method was used to analyze FBX in solubility samples. The quantitation of FBX was performed via ultra-violet (UV) detector at a wavelength of 354 nm. The entire estimation of FBX was performed at 298.2 K utilizing “HPLC system ”. The column “Nucleodur  reverse-phase C−1 using the potassium bromide disc technique as reported in literature [For pure FBX and equilibrated FBX (the solid recovered from bottom phase of equilibrated sample), Fourier transforms infrared (FTIR) spectroscopy and powder X-ray diffraction (PXRD) analyses were used to characterize the solid phases. Slow evaporation was used to recover the equilibrated FBX from water ,13. For terature . For PXR® WSB Shaking Water Bath ” [xe)” of FBX was computed by the following equation [m1 = FBX mass, m2 = solvent mass, M1 = FBX molar mass, and M2 = solvent molar mass.At 298.2–318.2 K and 101.1 kPa, the solubility of FBX in several mono solvents was measured using an experimental approach proposed by “Higuchi and Connors” . The ext Korea)” ,17. Eachequation :(1)xe=m1δ = total HSP of FBX; δd = dispersion HSP of FBX; δp = polar HSP of FBX, and δh = hydrogen-bonded HSP of FBX”.Drug compounds with similar solubility parameters could reach the maximum solubility in the sample matrices under standard conditions . As a reδ, δd, δp, and δh for FBX. These values were determined by putting the simplified molecular input line entry system (SMILES) of FBX into HSPiP software. The SMILES of FBX was taken from its PubChem data. However, the values of δ, δd, δp, and δh for various mono solvents were taken from reference [The “HSPiP software ” was used to calculate the values of eference .The following equation was used to calculate the “van Krevelen and Hoftyzer solubility parameter (∆δ¯)” :(3)∆δ¯=⌈1/2, the solubility of the solute in the mono solvent will be higher [Subscripts 1 and 2 denote the specific mono solvent and FBX, respectively. According to the literature if ∆e higher ,24.Ra)” [The following equation was used to compute the “three dimensional (3D) solubility parameter space (Ra)” ,26:(4)RaRa < 5.6 MPa1/2 [According to literature, the solubility of FBX in mono solvent will be higher if 6 MPa1/2 .δ)” was computed using the following equation [The “Greenhalgh’s solubility parameter (∆equation :(5)∆δ=δ2δ < 7.0 MPa1/2 [According to the literature, the solubility of FBX in mono solvent will be higher if ∆0 MPa1/2 ,27.xidl)” of FBX at 298.2–318.2 K [The following equation was used to compute an “ideal solubility (–318.2 K :(6)ln xiR is the universal gas constant, Tfus is the FBX fusion temperature, ∆Hfus is the FBX fusion enthalpy, and ∆Cp is the difference between FBX’s solid phase and liquid state molar heat capacity. The following equation was used to compute the ∆Cp for FBX [ for FBX ,29:(7)∆CTfus and ∆Hfus values for FBX were derived as 486.53 K and 27.58 kJ mol−1, respectively. Using Equation (7), the ∆Cp for FBX was estimated to be 56.68 J mol−1 K−1. Finally, using Equation (6), the xidl values for FBX were calculated.From reference , the Tfuγi)” for FBX in several mono solvents at 298.2–318.2 K [The following equation was used to calculate the “activity coefficients γiγi values of FBX at 298.2–318.3 K, FBX-solvent molecular interactions were estimated.Based on the computed λh, and Apelblat models” [xApl)” of FBX [For practical validations, computational analysis of experimental solubility of solutes is critical ,32. As a models” ,35,36,37” of FBX ,34:(9)lnA, B, and C are the model parameters obtained from the experimental FBX solubility data reported in xe and xApl values of FBX was carried out in terms of “root mean square deviation (RMSD) and R2”. The RMSD of FBX was computed using its reported equation [equation .xvan’t)” of FBX [The following equation was used to calculate the “van’t Hoff model solubility (” of FBX :(10)ln xa and b are the “van’t Hoff model” parameters, which were derived using “least square approach” [Here, pproach” .λh solubility (λhx)” for FBX [The following equation was used to calculate the “Buchowski-Ksiazczak  for FBX ,36:(11)lλ and h are the adjustable Buchowski-Ksiazczak λh model parameters.Here, solH0), apparent standard Gibbs energy (ΔsolG0), and apparent standard entropy (ΔsolS0)” for FBX were computed using “van’t Hoff and Krug et al. analysis” [solH0” for FBX in various mono solvents was computed at the “mean harmonic temperature (Thm)” of 308 K utilizing “van’t Hoff analysis” using the following equation [“Apparent thermodynamic analysis” was utilized to determine the thermodynamic characteristics of FBX in several mono solvents. Three different parameters, including “apparent standard enthalpy  [The “Δion (13) :(13)∆solHere, the intercept values for FBX in various mono solvents were derived from “van’t Hoff plots” included in solS0” for FBX dissolution [The following equation was used to calculate the “Δsolution ,38,39: ” was employed. A significant value was defined as a one with a Form A, form B, form C, and form H, for example, are polymorphic states of the FBX ,6. As a −1 (converted to 6.15 × 10−7 in mole fraction) [xe and 1/T and derived to be 6.23 × 10−7. The recorded value was closed to the reported value of FBX in water. At 298.2–318.2 K, the mole fraction solubility values of FBX in MeOH, EtOH, and EA have also been published [The measured solubility values of FBX in various mono solvents at 298.2–318.2 K and 101.1 kPa are summarized in p < 0.05) and was in good agreement with prior research [−2) > THP (1.70 × 10−2) > 2-BuOH (1.38 × 10−2) > 1-BuOH (1.37 × 10−2) > IPA (1.10 × 10−2) > EtOH (8.37 × 10−3) > EA (8.31 × 10−3) > DMSO (7.35 × 10−3) > MeOH (3.26 × 10−3) > PG (1.88 × 10−3) > EG (1.31 × 10−3) > water (1.14 × 10−6) at 318.2 K. Since PEG-400 has the maximum solubility of FBX compared to the other mono solvents tested, it may be the optimal solvent for FBX solubility.research ,17,18. Tδ value of 21.70 MPa1/2, indicating that it had a low polarity. Seven mono solvents such as IPA (δ = 22.30 MPa1/2), 1-BuOH (δ = 22.90 MPa1/2), 2-BuOH (δ = 20.80 MPa1/2), EA (δ = 18.10 MPa1/2), 1-DMSO (δ = 23.60 MPa1/2), THP (δ = 21.40 MPa1/2), and PEG-400 (δ = 18.90 MPa1/2) were discovered to exhibit similar δ values (lower polarities) and acceptable for FBX solubility. Water had a δ value of 47.80 MPa1/2, indicating that it was not suited for FBX solubility due to its greater polarity. It was discovered that if ∆1/2, the biomolecule’s solubility in the particular solvent will be greater [1/2 in all mono solvents investigated, showing that FBX is insoluble in all mono solvents according to this idea. It has also been discovered that if the value of Ra is <5.6 MPa1/2 the biomolecule’s solubility in the particular solvent will be greater [Ra values in three mono solvents, EA (Ra = 7.37 MPa1/2), THP (Ra = 7.81 MPa1/2), and DMSO (Ra = 7.97 MPa1/2), were found to be closed with 5.6 MPa1/2, showing that FBX is soluble in EA, THP, and DMSO according to this idea. However, the Ra values in other mono solvents were found to be much higher than 5.6 MPa1/2, indicating the insolubility of FBX in other mono solvents according to this concept. According to the Greenhalgh’s theory, the solubility of the biomolecule in the particular solvent will be higher if ∆δ is <7.0 MPa1/2. However, the value of ∆δ > 10.0 MPa1/2 has been proposed for the insolubility of biomolecule [δ value was determined to be maximum in water (∆δ = 26.10 MPa1/2), indicating the complete insolubility of FBX in water. While, the ∆δ value was determined to be lower in THP (∆δ = 0.30 MPa1/2), IPA (∆δ = 0.60 MPa1/2), 2-BuOH (∆δ = 1.10 MPa1/2), 1-BuOH (∆δ = 1.20 MPa1/2), DMSO (∆δ = 1.90 MPa1/2), PEG-400 (∆δ = 2.80 MPa1/2), EA (∆δ = 3.60 MPa1/2), and EtOH (∆δ = 3.70 MPa1/2), indicating the complete solubility of FBX in all of these mono solvents according to this concept [Different HSPs for FBX were determined using “HSPiP software”. The HSPs of different mono solvents were derived from reference . The val greater . The ∆δ¯ greater ,26. The molecule . The ∆δ  concept .xidl values for FBX. At 298.2–318.2 K, the xidl values for FBX were found to be 3.55 × 10−2 to 5.52 × 10−2. For FBX, the xidl values were found to be substantially greater than the xe values in water (p < 0.05). The xidl values of FBX, on the other hand, were found to be near to its xe values in PEG-400. PEG-400 was shown to be appropriate for the solubility of FBX based on these findings. The γi values for FBX in different mono solvents at 298.2–318.2 K are summarized in γi values for FBX were found to be substantially greater in water. With increasing temperature, the γi values of FBX in the mono solvents examined decreased significantly (p < 0.05). The γi values for FBX were found to be low in PEG-400, THP, and EA. Based on these results, the maximum solute-solvent interactions were observed in FBX-PEG-400, FBX-THP, and FBX-EA compared to other FBX-solvent combination.λh models” were employed to link FBX experimental solubility data in this study [xe and xApl values of FBX in several mono solvents against 1/T, which showed a high correlation between the xe and xApl data of FBX in several mono solvents. The results of Apelblat model computation are included in RMSD for FBX was determined to be 1.14%. R2 values for FBX in various mono solvents range from 0.9919 to 0.9999. The low RMSD values and higher R2 values revealed that the experimental solubility data of FBX in the mono solvents was well correlated with the Apelblat model.Three computational models namely, “van’t Hoff, Apelblat, and Buchowski-Ksiazaczak is study ,35,36,37xe and xvan’t values of FBX in several mono solvents against 1/T, which also showed a high correlation between xe and xvan’t values of FBX in all mono solvents. The results for the van’t Hoff model computation for FBX in various mono solvents are summarized in RMSD for FBX in various mono solvents was determined to be 1.60%. R2 values for FBX in several mono solvents range from 0.9920 to 0.9998. The low RMSD values and higher R2 values again revealed that the experimental solubility data of FBX in mono solvents was well correlated with “van’t Hoff model”.λh computation for FBX in numerous mono solvents. In numerous mono solvents, the overall RMSD for FBX was found to be 2.86%. The low RMSD values again showed a high correlation of experimental solubility data of FBX in numerous mono solvents with “Buchowski-Ksiazaczak λh model”. Overall, all three computational models performed well in the solubility correlation of FBX.solH0 values for FBX in various mono solvents were determined from the van’t Hoff graphs, included in solH values in numerous mono solvents recorded as positive values in the range of 24.50–68.79 kJ mol−1. The FBX ΔsolG0 values in numerous mono solvents were also recorded positive values in the range of 10.38–37.21 kJ mol−1. The FBX ΔsolG0 values were found to be lowest in PEG-400 and highest in water, which could be attributed to FBX solubility being highest in PEG-400 and lowest in water, respectively. The positive values of ΔsolH0 for FBX suggested that FBX dissolution was an endothermic in the mono solvents examined [solS0 values in numerous mono solvents were also recorded as positive values in the range of 37.30–157.6 J mol−1 K−1, suggesting an entropy-driven FBX dissolution in all mono solvents examined [solH and ΔsolS0, the FBX dissolution was considered to be an endothermic and entropy-driven in all mono solvents examined [The Δexamined . The FBXexamined .λh models”. The solubility of FBX increased with increasing temperature in all mono solvents examined. The order of solubility of FBX in various mono solvents was PEG-400 > THP > 2-BuOH > 1-BuOH > IPA > EtOH > EA > DMSO > MeOH > PG > EG > water at 318.2 K. When comparing FBX-PEG-400, FBX-THP, and FBX-EA to other combinations of FBX and mono solvent, the findings of activity coefficients showed that FBX-PEG-400, FBX-THP, and FBX-EA had the most molecular interactions. Thermodynamic study indicated an “endothermic and entropy-driven dissolution” of FBX in all mono solvents examined. Based on overall results, PEG-400 has been selected as the best cosolvent for the solubility of FBX. As a consequence, PEG-400 can be used as a potential co-solvent in pre-formulation studies and formulation development of FBX.The solubility values, HSPs, and thermodynamics properties of FBX in various mono solvents were investigated. FTIR and PXRD spectral analyses validated the solid state form of FBX, which revealed no alteration of FBX after equilibrium. The results on FBX solubility was strongly associated with the “van’t Hoff, Apelblat, and Buchowski-Ksiazczak


The COVID-19 pandemic has put the world's survival in jeopardy. Although the virus has been contained in certain parts of the world after causing so much grief, the risk of it emerging in the future should not be overlooked because its existence cannot be shown to be completely eradicated.This study investigates the impact of vaccination, therapeutic actions, and compliance rate of individuals to physical limitations in a newly developed SEIQR mathematical model of COVID-19. A qualitative investigation was conducted on the mathematical model, which included validating its positivity, existence, uniqueness, and boundedness. The disease-free and endemic equilibria were found, and the basic reproduction number was derived and utilized to examine the mathematical model's local and global stability. The mathematical model's sensitivity index was calculated equally, and the homotopy perturbation method was utilized to derive the estimated result of each compartment of the model. Numerical simulation carried out using Maple 18 software reveals that the COVID-19 virus's prevalence might be lowered if the actions proposed in this study are applied.It is the collective responsibility of all individuals to fight for the survival of the human race against COVID-19. We urged that all persons, including the government, researchers, and health-care personnel, use the findings of this research to remove the presence of the dangerous COVID-19 virus. COVID-19 infection has spread to every continent. New coronavirus hotspots were detected in Wuhan, China, in December 2019. When numerous people were admitted to the hospital in late December 2019, it was clear that the pandemic had begun. By mid-July 2020, the virus had infected over 213 countries, causing 15,969,465 infections and 643,390 fatalities . Equation , e[0](t) = e[0], e[1](t) = (-Pi*e[0]+beta*s[0]*i[0]-e[0]*mu-e[0]*gamma-beta*c*s[0]*i[0])*t, e[2](t) = (1/2)*t^2*(-beta^2*c^2*i[0]^2*s[0]-3*beta*i[0]*mu*s[0]-beta*i[0]*rho*s[0]+2*beta^2*i[0]^2*c*s[0]-beta*c*i[0]*Lambda-beta*s[0]*Pi*i[0]-gamma*beta*s[0]*i[0]-beta*s[0]*sigma*i[0]+e[0]*gamma^2+e[0]*Pi^2+beta*s[0]*Pi*e[0]+2*e[0]*mu*Pi-beta^2*i[0]^2*s[0]+e[0]*mu^2-beta*s[0]*r*i[0]+beta*i[0]*Lambda+2*e[0]*gamma*mu+2*e[0]*gamma*Pi-Pi*beta*c*s[0]*e[0]+beta*c*s[0]*sigma*i[0]+Pi*beta*c*s[0]*i[0]+gamma*beta*c*s[0]*i[0]+3*beta*c*i[0]*mu*s[0]+beta*c*i[0]*rho*s[0]+beta*c*s[0]*r*i[0]), i[0](t) = i[0], i[1](t) = (Pi*e[0]-sigma*i[0]-i[0]*r-i[0]*mu)*t, i[2](t) = -(1/2)*t^2*(e[0]*Pi^2-beta*s[0]*Pi*i[0]+2*e[0]*mu*Pi+e[0]*gamma*Pi+Pi*beta*c*s[0]*i[0]+sigma*Pi*e[0]-i[0]*sigma^2-2*i[0]*r*sigma-2*i[0]*mu*sigma-2*i[0]*r*mu-i[0]*mu^2+r*Pi*e[0]-i[0]*r^2), q[0](t) = q[0], q[1](t) = (e[0]*gamma-q[0]*theta-mu*q[0]+sigma*i[0])*t, q[2](t) = -(1/2)*t^2*(2*e[0]*gamma*mu-2*q[0]*theta*mu-mu^2*q[0]+2*i[0]*mu*sigma+e[0]*gamma*Pi-gamma*beta*s[0]*i[0]+e[0]*gamma^2+gamma*beta*c*s[0]*i[0]-sigma*Pi*e[0]+i[0]*sigma^2+i[0]*r*sigma+theta*gamma*e[0]-q[0]*theta^2+theta*sigma*i[0]), r[0](t) = r[0], r[1](t) = (rho*s[0]-mu*r[0]+i[0]*r+q[0]*theta)*t, r[2](t) = (1/2)*t^2*(-2*mu*rho*s[0]+r[0]*mu^2-2*i[0]*r*mu-2*q[0]*theta*mu+theta*gamma*e[0]-q[0]*theta^2+theta*sigma*i[0]+Lambda*rho-rho^2*s[0]+beta*c*i[0]*rho*s[0]-beta*i[0]*rho*s[0]+r*Pi*e[0]-i[0]*r*sigma-i[0]*r^2), s[0](t) = s[0], s[1](t) = (Lambda-mu*s[0]-rho*s[0]+beta*c*s[0]*i[0]-beta*s[0]*i[0])*t}>S3: =dsolve, t)-mu*s[2](t)+beta*s[0](t)*i[2](t)-beta*c*s[1](t)*i[1](t)+rho*s[2](t)-beta*c*s[0](t)*i[2](t) beta*c*s[2](t)*i[0](t)+beta*s[2](t)*i[0](t)+beta*s[1](t)*i[1](t), ic), s[3](0) = 0});>E3: =dsolve, t)-beta*s[1](t)*i[1](t)+beta*c*s[1](t)*i[1](t)+beta*c*s[2](t)*i[0](t)-beta*s[2](t)*i[0](t)+gamma*e[2](t)+beta*c*s[0](t)*i[2](t)-beta*s[0](t)*i[2](t)+mu*e[2](t)+Pi*e[2](t), ic), e[3](0) = 0});> Iota3 := dsolve, t)+mu*i[2](t)-Pi*e[2](t)+sigma*i[2](t)+ +r*i[2](t), ic), i[3](0) = 0});> Q3 := dsolve, t)+mu*q[2](t)+theta*q[2](t)-sigma*i[2](t)-gamma*e[2](t), ic), q[3](0) = 0});>R3:= dsolve+mu*r[2](t)-r*i[2](t)+diff(r[3](t), t)-theta*q[2](t), ic), r[3](0) = 0});This continues till the desired number of iteration is computed. For the purpose of this research, we performed three iterations. Due to cumbersome number of terms, we present the iteration code instead of the computed results.The solution for each class is obtained by taking the sum of its obtained approximations such that: Additionally, the outcome is assessed to project the dynamics of the disease using actual data from the Nigeria Center for Disease Control (NCDC) report from December 1, 2020. )=470200 :\documenThe convergence of the homotopy perturbation approach strictly depends on the contraction of the approximation solution to the exact solution .Let there exist a mapping cument}k .The proof is defined by applying mathematical induction on the contractive property of contraction c such that We consider a Picard sequence This proves that The proposed mathematical model's convergence of (i)The nth-order derivative of  to t in  must be (ii)ii. The rate of convergence of ed by He , 26:(i)TThis rate is examined in the following section.In numerical computations of series solutions, error analysis is crucial. In this section, we utilize the convergence requirements from Lemma The truncation error of an To compute the third-order maximum truncation error of the model's class series results on the interval The error analysis of the approximate series results demonstrates that the model is validated for actual data simulation since the error generated by the third-order approximation is negligible. We observed that the maximum error is recorded in the susceptible and exposed compartments. This happens because the two classes contain nonlinear variables Tables ; Fig. 1.In this section, we execute numerical simulations of the mathematical model to rigorously investigate the influence of the incorporated parameters entclass1pt{minimamentclasspt{minimaIn this section, we assess the model's validity by numerically projecting active infected cases for 30 days using the baseline parameters given in Table The results of the numerical simulations are discussed in this section. The restriction on population-wide physical contact, extensive imposition of immunization, and the intense care given to the sick patients were all clearly examined and recorded to have increased the number of susceptible and recovered individuals in a COVID-19-enraged population. Remarkably, we observed that the findings of this analysis are consistent with those of earlier research , raisingEpidemic infections, such as COVID-19, cannot be totally eradicated by a single factor. The objectives of this research were achieved as the numerical simulation analysis unconditionally showed the dynamics of COVID-19 spread under different control situations. We also showed that the combined application of vaccine, therapy, and human compliance factors to COVID-19 curfew and social distancing rules has an appreciable effect in stopping the disease's global existence. The mathematical model’s validity and error analysis showed that the model could be applied for further studies on coronavirus disease as it depicts the behavior of real-life COVID-19 situations.To eradicate the COVID-19 virus, we recommend that governments around the world give immunizations to their vulnerable populations on high range. Furthermore, hospitals should provide superior health-care facilities as well as advanced life-saving technology capable of treating sick people flawlessly. Furthermore, it is critical to underline that governments' efforts to restrict the transmission of the virus can only yield beneficial results if the populace has a receptive attitude toward avoiding disease contact. To constantly eliminate the disease's existence, it is thus recommended that everyone obey curfew, isolation, and the use of nose masks, among other things.Although this study demonstrated the diverse reactions of an endangered population to therapy, physical contact limitation, and immunization in a COVID-19-exhibited environment, future research could incorporate introduction of second-stage immunization strategy as well as incidence rate capturing fear of disease transmission. Also, fractional-order analysis of the current mathematical model employing fractional operators like Caputo , Caputo–


We present a novel combination of water-based poly(ionic liquid) and imidazolium-based ionic liquids (Emim[X]). Poly/Emim[X] capsules were developed for the first time using Nano Spray Dryer B-90. Capsules were characterized by FTIR, SEM/EDX, TEM, TGA, DSC, CO2 sorption, and CO2/N2 selectivity, CO2 sorption kinetic and recycling were also demonstrated. Comparing the capsules reported in this work, the combination of poly and the ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate (P[DADMA]/BF4) showed great potential for CO2 capture and CO2/N2 separation, providing higher results .Encapsulated ionic liquids as green solvents for CO CO2 capture and storage technologies are suggested as the easiest and most effective way to reduce CO2 emissions at a large scale [BnIm] and [P2228][2CNPyr] perfomed similar or even better for CO2 sorption than aqueous amines at low pressure and 25 °C  (95%), 1-Ethyl-3-methylimidazolium trifluoromethanesulfonate, Emim[CF3SO3] (98%), were purchased from Merck. The chemicals were used without further purification. CO2 (99.8%) and CO2/N2  were purchased from White Martins.Aqueous solution of poly, P[DADMA][Cl] , Lithium tetrafluoroborate salt (98%), 1-Ethyl-3-methylimidazolium methanesulfonate, Emim[MSO4]), used as shell material, was obtained by anion exchange from Li[BF4] and an aqueous solution of poly, P[DADMA][Cl], following literature procedures [4]), used as core, were synthesized as described in literature [4]: 1H NMR 1.43 , 3.84 , 4.15 , 7.37 , 7.43 , 8.63 .First, the Poly(ionic liquid) poly  equipment. The materials structure of encapsulated ionic liquids (ENILs) can be observed in Ionic liquid Emim[X] was encapsulated in P[DADMA][BF4] was dissolved in distilled water under mild heating. After complete dissolution, the ionic liquid was added and the solution was stirred until the complete homogenization. The solution was fed to the atomization system using a peristaltic pump. Mass proportion of P[DADMA][BF4]:Emim[X] was 1:0.5. Nano Spray Dryer process parameters  was calculated by equation n method ; wIL-e: Aiming to compare results for both configurations – capsules and the pristine PIL (P[DADMA]-poly) – capsules were obtained (without IL - P[DADMA]-cap). Sample code and its components are shown in 2.32 sorption tests were performed using the well-known pressure decay technique -cap (1: ∼665 nm (+-266); 1: ∼695 nm (+-190); 1: ∼ ∼678 nm (+-222); 1: ∼718 nm (+-260); e 1: ∼931 nm (+-300)). EDX ). EDX  confirmeIn terms of shape and construction, particles can be called capsules or spheres. For capsules, the confined liquid is surrounded by a well-defined polymer line, while for spheres, the core and shell are mixed . Capsule4] shell. All samples showed characteristic peaks of (see −1 (C–H of N–CH2), 2946–2869 cm−1 (C–H of CH3), 1482–1387 cm−1 (C–H), 1286 cm−1 (N–C); and tetrafluoroborate anion: 1037-897 cm−1 (B–F) : 757 cm−1 (C–S); [CF3SO3]: 1055 cm−1 (SO), 754–631 cm−1 (C–F); [Br]: 617 cm−1. Other bands indicate O–H deformations, referring to water.FTIR also confirmed Emim[X] encapsulation within the P[DADMA]- remotion and the loss of two methyl groups. The second Tonset2, at 486.6 °C, refers to the complete polymer degradation -poly: 35.65 (±0.42) mg/g; P[DADMA]-cap: 47.88 (±1.55) mg/g) and CO2/N2 selectivity (P[DADMA]-poly: 2.05 (±0.23); P[DADMA]-cap: 3.81 (±0.14)) is noticed when comparing two different configuration of poly(ionic liquid) in capsule (P[DADMA]-cap) and solid polymer (P[DADMA]-poly), suggesting capsule formation can increase the active surface area, improving gas contact [2 sorption best results were found for P[DADMA]/BF4 (53.40 (±0.39) mg/g) and P[DADMA]/CF3SO3 (51.76 (±0.26) mg/g), representing statistical equality (see 2 permeability and diffusivity (μ (mPa.s): Emim[BF4] = 20.41 (40 °C) [3SO3] = 23.86 (45 °C) [3] = 69 (45 °C) [2 affinity [2 sorption results. Higher CO2/N2 selectivity was evidenced by P[DADMA]/BF4 (4.58 (±0.39)). ILs with smaller and symmetric anions tend to favor cavity creation and consequently a closer contact with CO2, improving CO2/N2 selectivity [4] best performance.An increase in CO contact ,18. IL elity see . Ionic l (40 °C) ; Emim encapsulation with poly as shell appears as a potential option for CO2 capture. The CO2 sorption capacities of samples obtained in this work are higher compared with some results reported in the literature, under similar conditions (Emim[BFnditions .Table 4C2 sorption capacity of encapsulated ionic liquid tends to increase when compared with pristine ionic liquids. The encapsulation of Emim[BF4] (P[DADMA]/BF4) increased, approximately, four times the CO2 solubility when compared with the CO2 sorption capacity of the pristine IL Emim[BF4] reported in literature /BF capture ; Fig. S4perature , typical2 capture. P[DADMA]-cap and P[DADMA]/BF4 were tested for ten cycles of CO2 sorption/desorption and from 2 soption capacity of both are still the same, keeping the deviation stability  P[DADMA]. Bárbara B. Polesso was supported by capes [001]. Professor Sandra Einloft was supported by CNPq [316580/2021-0]. This work was supported by fapergs [21/2551-0002235-3].Rafael Duczinski was supported by Data included in article/supp. material/referenced in article.The authors declare no competing interests.


In the title phenothiazine derivative, the heterocycle displays a butterfly conformation. 20H12N2OS, is a 10-ethynyl-10H-phenothiazine derivative. The phenothiazine unit has a butterfly shape, where the folding angle between the two benzene rings is 153.87 (7)°, which is almost as in other reported phenothiazine derivatives. The dihedral angle between the mean plane including the C atoms bonded to the phenothiazine N atom and the benzene ring of the nitrobenzene group is 10.34 (5)°. The near planar geometry of the molecule is reasonably explained by intramolecular charge-transfer interactions.The title compound, C The solution was stirred for 20 h and filtrated. The filtrate was concentrated and the residue was extracted with CHCl3. The organic layer was washed with water, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by gel permeation chromatography to give 32 mg (6.9% yield) of the title compound, as pale-red crystals. 1H NMR (CDCl3): δ = 8.21 , 7.58 , 7.48 , 7.26 , 7.17 , 7.10 .Single crystals suitable for X-ray analysis were obtained by concentration of a dichloromethane solution. The title compound was prepared through the Sonogashira-coupling reaction between 1-iodo-4-nitrobenzene and 10-ethynyl-10Crystal data, data collection and structure refinement details are summarized in Table 110.1107/S2414314622009427/bh4070sup1.cifCrystal structure: contains datablock(s) I. DOI: 10.1107/S2414314622009427/bh4070Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2414314622009427/bh4070Isup3.cmlSupporting information file. DOI: 2209381CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


A. consanguineum.The study was planned to investigate the phytochemicals, antidiabetic and antioxidant studies of 2O2) were performed on all samples. The in-vivo experiments on compounds 1 and 2 were also performed using oral glucose tolerance test. Docking studies were performed on α-glucosidase and α-amylase targets.The preliminary studies were performed on crude extract and different solvent fractions. Based on the potency, the chloroform fraction was semi-purified to phyto-fractions CHF-1 – 5. Furthermore, CHF-3 was subjected to isolation of pure compounds using column chromatography. The α-glucosidase, α-amylase and antioxidant assays , CHF-3 was the leading fraction in activities giving IC50 values of 85.54, 61.19 and 26.58 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Based on the overall potency and physical amount of CHF-3, it was subjected to purification to get compounds 1 and 2. The two compounds were also found potent in in-vitro activities. The observed IC50 values for compound 1 were 7.93, 28.01 and 6.19 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Similarly, the compound 2 exhibited IC50 of 14.63, 24.82 and 7.654 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Compounds 1 and 2 were potent in decreasing the blood glucose levels in experimental animals. Compounds 1 and 2 also showed interactions with the respective enzymes with molecular docking.Among all fractions, the chloroform fraction exhibited excellent activities profile giving ICA. Consanguineum is a rich source of natural antidiabetic agents. Bioguided isolation of compound 1 and 2 showed potential inhibitions in all tested in-vitro antidiabetic targets. Further, both the compounds were also able to decrease the blood glucose levels in experimental animals.We can conclude that  From centuries, herbal treatments have been used as medication in different diseases. Due to their harmless effect comparatively, the natural products have gained the attention of the new scientists in the cure and management of different challenging ailments . AccordiEtiology of “T1DM is result of an autoimmune reaction to proteins found in the islets of Langerhans of the pancreas  and T2DMEpidemiologically (diabetes is a disorder of endocrine system that affects about 6% part of the world’s population and is increasing daily) . The occIn 2010, the number of patients with T1DM was reported to 285 million people worldwide, including 90% of people with T2DM. The estimated rate of diabetes for 2030 is about 439 million worldwide, which It represents 7.7% of the global adult population (20–79) . In PakiFree radicals are the cause of various issues in humans’ inclusive injury of the nervous system, atherosclerosis, ischemic coronary heart diseases, cancer, arthritis, gastritis, and reperfusion damaging of various tissues –17. FreeAllium consanguineum is specie of the Amaryllidaceae family. The epidermal anatomy of the leaf of A. consanguineum was the most diverse. The stomatal cells in this species were the longest, measuring 6–14 μm dioxole. The MS spectrum of compound 2 showed molecular ion peak at 222 (100%) with fragmentation pattern of 207 (20%), 191 (8%), 177 (41%), 161 (6%), 149 (126%), 134 (12%), 106 (22%), 91 (18%), 77 (28%) and 51 (16%). The most dominant peak of compound 2 was the methylene unit  with ICn-hexane, chloroform, ethyl acetate, aqueous were tested at various concentrations of 62.5 μg/ml, 125 μg/ml, 250 μg/ml, 500 μg/ml and 1000 μg/ml caused a percent radical scavenging of 71.16 ± 0.44, 63.06 ± 0.63, 52.66 ± 0.88, 44.83 ± 0.72, 38.50 ± 0.28, (IC50 168 μg/ml),65.26 ± 0.37, 54.33 ± 0.88, 45.73 ± 0.37, 34.66 ± 1.20, 29.83 ± 0.72 (IC50 356 μg/ml),68.66 ± 0.88, 59.10 ± 0.49, 49.40 ± 0.94, 41.56 ± 0.86,36.10 ± 0.49 (IC50 117 μg/ml),74.06 ± 0.52, 66.66 ± 0.88, 59.50 ± 0.28, 52.16 ± 0.72, 47.66 ± 1.20(IC50 265 μg/ml), 56.63 ± 0.68, 47.16 ± 0.44, 41.73 ± 1.15, 33.40 ± 0.83, 26.66 ± 0.88 (IC50 650 μg/ml)respectively. The inhibition of all fractions was significant at the highest concentration when compared to the positive control as shown in Table The antioxidant results of the three methods are summarized in Table n-hexane, chloroform, ethyl acetate, aqueous fractions at tested concentrations (62.5–1000 μg/ml) proved a percent inhibition of 68.00 ± 0.57, 64.63 ± 0.48, 57.96 ± 0.12, 48.66 ± 0.88, 43.26 ± 0.32 (IC50 148 μg/ml), 51.07 ± 1.02, 45.33 ± 0.33, 37.20 ± 0.91, 33.46 ± 0.54, 28.63 ± 0.48 (IC50 937 μg/ml), 77.43 ± 0.61, 73.26 ± 0.32, 65.56 ± 0.40, 59.03 ± 0.38, 55.46 ± 0.54 (IC50 58 μg/ml), 68.46 ± 0.50, 54.16 ± 0.85, 52.63 ± 0.52, 47.02 ± 1.11, 42.03 ± 0.38 (IC50 186 μg/ml), 46.66 ± 0.33, 41.00 ± 0.57, 32.66 ± 0.58, 29.13 ± 0.88, 25.20 ± 0.91, (IC501354 μg/ml)free radicals respectively (Table 50 < 0.1).In comparison to the DPPH results, plant extracts showed significant ABTS free radical scavenging activity. Using this assay, methanolic, 50 85 and 194. Among all fractions chloroform fraction showed comparable results with standard drug ascorbic acid having the IC5012.63 . The potent phyto-fraction (CHF-3) gave percent inhibitions of 71.23, 65.45, 61.90, 54.00 and 45.90% at concentrations of 1000, 500, 250, 125 and 62.5 μg/ml. All the other phyto-fractions were also very good in alpha glucosidase inhibitions. The observed IC50 values for CHF-1, CHF-2, CHF-4 and CHF-5 were 155.39, 87.45, 316.28 and 139.72 μg/ml. The activities of all the phyto-fractions were compared with the standard acarbose at the same tested concentrations and observed an IC50 value of 12.57 μg/ml.The α-glucosidase results of the semi-purified chloroform fractions are summarized in Table 50 values of 61.19 and 58.34 μg/ml respectively. At maximum concentration, CHF-3 and CHF-5 gave percent inhibitions of 76.76 and 74.46% respectively. The observed IC50 values for phyto-fractions CHF-1, CHF-2 and CHF-4 were 83.03, 78.80 and 99.19 μg/ml respectively. In comparison, the standard drug gave IC50 value of 13.13 μg/ml.The alpha amylase inhibition results of the semi-purified phyto-fractions (CHF-1 to CHF-5) are provided in Table 50 values than alpha glucosidase and amylase. The CHF-3 was again observed to be most potent giving IC50 value of 26.58 μg/ml. This phyto-fraction gave inhibitions of 81.85, 76.59, 69.75, 64.47 and 59.12% at 1000, 500, 250, 125 and 62.5 μg/ml respectively. The potencies of other phyto-fractions were in an order of CHF-5 > CHF-4 > CHF-2 > CHF-1 as obvious in Table 50 value of 4.32 μg/ml.Obviously, it can be concluded from the published literature related to the free radicals’ role in antidiabetic that the antioxidant protects the beta cell, and thus can be helpful as supplement in antidiabetic treatment. The antioxidant results using DPPH free radicals are summarized in Table 50 values of 7.93 and 14.63 μg/ml respectively in comparison to the standard acarbose (IC50 12.57 μg/ml).Similarly, in alpha amylase target, the compounds 1 and 2 were almost equally potent giving IC50 values of 28.01 and 24.82 μg/ml respectively. To check the possible supplementary role of isolated compounds in inhibiting the free radicals, the DPPH assay was also accompanied herein. The compound 1 was potent antioxidant compared to 2 giving IC50 value of 6.19 μg/ml.Based on the potency of phyto-fraction CHF-3 in tested in-vitro assays, this fraction was further subjected to isolate compounds 1 and 2. The two compounds were also tested against alpha glucosidase, alpha amylase and DPPH targets Table . The pur0 to LD100. For the isolated compounds 1 & 2, the detailed dosing regimen is presented in Table The doses were in the range of 200–1500 mg/kg body weight were selected on the basis of the acute toxicity series finding LD50).Initially, all the animals under acute toxicity observations were checked for behavioral and other effects. The observations were continued for 3 days. It was observed that no abnormalities were found in animals. So, a dose of 1000 mg was considered to be safe in experimental animals as this was roughly considered as the lethal dose , which can lead to diseases such as diabetes, coronary heart disease, cancer, neurodegenerative disorders (Alzheimer’s and dementia), immune suppression, atherosclerosis, ulcers and aging . Hydroxyl cation .The α-glucosidase and α-amylase assays are very common and well-known tests for determining the preliminary antidiabetic activity of an unknown compound . The in-The molecular docking is one of the reliable approaches to find out the interaction of a molecule with the binding protein for the management of various ailments –58. We hAllium consanguineum for the management of diabetes.Based on our results, it can be assumed that the most of plant fractions that were examined herein have strong antioxidant capacity, which can be linked to the presence of high molecular weight phenolics. The plant also exhibits dose-dependent inhibitory action against alpha glucosidase and alpha amylase enzymes. Based on the relative potency of chloroform fractions, it was semi-purified to five different phyto-fractions CHF-1 to 5. The five phyto-fractions were relatively dominant in tested in-vitro targets. Among those, CHF-3 was dominant in activities due to the presence of bioactive compounds. The CHF-3 was purified to obtained compounds 1 and 2. The two compounds were excellent in in-vitro antidiabetic assays. Computed binding energy values of compounds 1 and 2 via docking studies revealed that both compounds may have strong synergistic effects in lowering the blood glucose level. The two compounds were also dominant in lowering the blood glucose levels in experimental animals. The study provides a baseline guideline for the use of crude extract and isolated compounds of