ABCG8 gene, which led to the diagnosis of sitosterolemia. The aim of our report is to demonstrate, how genetic testing helped to make the correct diagnosis and to explain many of the patient's health problems, which etiology remained unclear for many years.We reported a case of sitosterolemia, which is a rare genetic disease, characterized by increased plant sterol absorption and great heterogeneity of clinical manifestations. Our patient was initially referred to the lipid clinic due to high cholesterol levels and premature cardiovascular disease. Diagnosis of familial hypercholesterolemia was established in accordance with the Dutch Lipid Clinic Network criteria. Next-generation sequencing was later performed, which revealed a nonsense mutation in the  ABCG5 and ABCG8). Although recent data suggest that not only homozygous but also heterozygous carriers of ABCG5 loss-of-function variants exhibit increased plant sterols and LDL-C levels and have increased risk of coronary artery disease (CAD), compared with non-carriers  of plant sterols are absorbed, with further quick excretion into the bile from hepatocytes . Disruptcarriers . These pcarriers , 5. Thus% of planIn this report, we presented a case of a patient with sitosterolemia and discuss mechanisms of different clinical manifestations of the disease, present in our patient. We aimed to demonstrate how next-generation sequencing (NGS) helped to make the correct diagnosis, which explained all the symptoms, present in this patient and which etiology remained unclear for many years.2. She had exertional dyspnea since adolescence. Hypercholesterolemia was revealed at the age of 34 years old . Two years later, due to the onset of angina and ischemic changes on ECG during physical activity, coronary arteriography was performed. It revealed 80% stenosis of the left main coronary artery, 80% stenosis of the anterior descending artery, occlusions of the proximal right coronary artery, the diagonal branch, and the obtuse marginal branch. At that time the duplex sonography revealed no atherosclerotic manifestations of other vascular territories (carotids and lower extremity arteries). Coronary artery bypass grafting (CABG) was performed. During the first 2 days after CABG, the patient had hemopericardium and hemothorax. She was diagnosed with intracerebral hemorrhage 10 days later.A 41-year-old woman was referred to the lipid clinic due to her elevated cholesterol level. On examination, she had tendinous xanthomas of the Achilles tendons. Her body weight was 59 kg, and her height was 1.67 m, with a body mass index of 21.2 kg/mOn rosuvastatin 20 mg and ezetimibe 10 mg, which were initiated 1 year before the current presentation, her total cholesterol was 6.7 mmol/L, LDL-C - 3.95 mmol/L, HDL-C – 2.3 mmol/L. During follow-up with a cardiologist paroxysmal atrial fibrillation was diagnosed. Three years after CABG, the stress testing was performed with positive results. One year later, the CT-angiography revealed subtotal stenosis of the left main coronary artery, with normally functioning bypass grafts to the left anterior descending artery and right coronary artery. Duplex sonography demonstrated stenosis of carotid bifurcations and proximal internal carotid arteries up to 30% at the right and 35% at the left, and 35% stenosis of the left vertebral artery.*9/L and MPV 14.7 fL), arthralgia of knee joints, and past recurrent serositis (pericarditis and pleurisy). The latter was treated with fluoroquinolones and prednisolone. Cardiolipin antibodies and anti-dsDNA test results were negative. No definite diagnosis was established. Due to the polycystic ovary syndrome, the resection of ovaries was fulfilled at the age of 23. Her gynecologic history was also noteworthy for frozen pregnancy of unknown etiology, weak labor activity which led to caesarian section , and early menopause at 39 years old.Her medical history was also significant for macrothrombocytopenia (with current PLT 113 x 10Her family history was unremarkable with no information about premature CAD.According to the Dutch Lipid Clinic Network criteria (16 points) heterozygous familial hypercholesterolemia (HeFH) was diagnosed. Maximum statin dose, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were prescribed and cascade screening was recommended.ABCA1, ABCG5, ABCG8, ANGPTL3, APOA1, APOA5, APOB, APOC2, APOC3, APOE, CETP, GPD1, GPIHBP1, LCAT, LDLR, LDLRAP1, LIPC, LIPI, LMF1, LPL, MTTP, PCSK9, SAR1B, STAP1, USF1) and 280 variants responsible for the lipid metabolism.Later on, the NGS was performed using the Ion S5 . Ampliseq libraries were prepared on the Ion Chef System  using the custom panel, created with the Ion AmpliSeq Designer , which consists of 25 genes (CETP)  and apolipoprotein B (ApoB)  genes were revealed, wherein both were classified as variants of uncertain significance according to the American College of Medical Genetics and Genomics guidelines (ACMG2015). Pathogenic or likely pathogenic variants in LDLR, PCSK9, APOB, and LDLRAP1 were not detected. The patient was found to be homozygous for a nonsense mutation in the ABCG8 gene , leading to premature termination of signal codon 361 . This odyssey is, undoubtedly, a real burden for patients suffering from misdiagnoses and inappropriate treatment and for the healthcare system. For example, as described by Wang et al. in their series of cases, the mean ages of symptoms onset were 15.2 years, and the mean years of delay between symptom onset and diagnosis were 28.8 (range 15–49 years)  is not described in gnomAD, where another substitution  was previously described with total frequency <0.01. SNPs, reported at http://www.hgmd.cf.ac.uk/ as associated with decreased CETP activity/increased HDL-C, are often located at beta strands within the protein sequence. Two hundred and thirty six amino acid position is also located at the beta-strand region. Thus, the patient's phenotype (HDL-C - 2.3 mmol/L) could be explained by this missense variant.The missense variant in the Clinical data regarding atherosclerosis development vary from early myocardial infarction and sudden cardiac death at the age of 5  to no clThe same clinical heterogeneity is true about xanthomas , 27. OurFrom enterocytes plant sterols, as well as cholesterol esters, proceed to chylomicrons which are further metabolized in the liver. Lipoprotein-derived cholesterol and plant sterols can further penetrate the artery wall and lead to inflammation and atherosclerotic plaque progression . In caseSimilar mechanisms could be involved in xanthomas formation, as early stages of their formation resemble early stages of atherogenesis . MoreoveABCG5/ABCG8 with non-HDL cholesterol, a plant sterols, and the risk of CAD. They demonstrated that the degree of CAD risk conferred by ABCG5/ABCG8 variants is greater than predicted by their effect on non-HDL cholesterol levels only. The authors concluded that plant sterols may contribute to atherogenesis directly, irrespective of non-HDL cholesterol  and coronary heart disease . Wu et al.  resulted in a more than 2-fold greater risk of developing CAD, compared with those who carried the A allele in a dominant model. The multivariate analysis supported that such an effect was independent of several other risk factors, including age, gender, history of diabetes mellitus, and HDL-C level.In a recent genetic study, based on data from biobanks of Iceland, Denmark, and UK Biobank, authors evaluated the association of variants in lesterol . Koeijvolesterol  studied Our patient has a compromised gynecological anamnesis. As complete medical records of that period were unavailable, we can't definitely conclude, whether or not her gynecological anamnesis could be related to her main disease or some other problem. Anyway, we suppose that this aspect of her health problems is worth mentioning and discussing in light of high plant sterol levels.ABCG5/ABCG8 knock-out mice fed with a diet high in plant sterols were infertile. Exclusion of plant sterols from diet or blockage of their absorption (with ezetimibe) could restore fertility. No structural abnormalities of the ovaries were found. Oxidation products of plant sterols have been reported to modulate the action of 17β-estradiol in vitro and two human cell lines  for the publication of any potentially identifiable images or data included in this article.AL was treating the patient, performing her follow-ups, and writing this paper. AE was treating the patient, supervising all parts of this paper's preparation, and edited this paper. AM supervised the genetic testing of the patient and provided valuable comments on this case. AK performed the NGS and edited this paper. MD performed the Sanger sequencing. OD is the chief of the center who provided valuable comments on this case. MK performed the development of a method for the determination of plant sterols and performed determination of their concentration of phytosterols. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


RAASi treatment was discontinued in 55.3% of the patients after hyperkalemia event . This study shows that the incidence of hyperkalemia is frequently observed in patients with CKD patients with RAASis, and that rates increase with deteriorating levels of kidney function from stages 1 to 3. RAASi medication change following an episode of hyperkalemia occurred in almost half of the patients after experiencing hyperkalemia.Hyperkalemia is common in patients treated with renin–angiotensin–aldosterone system inhibitors (RAASis), and it represents the main cause of the large gap reported between guideline recommendations and real-world practice in chronic kidney disease (CKD). We conducted a CKD-population-based restrospective study to determine the prevalence of patients with CKD treated with RAASis, incidence of hyperkalemia in patients with CKD treated with RAASis, and proportion of patients with RAASi medication change after experiencing incident hyperkalemia. Among 809 patients with CKD analyzed, 556 (68.7%) were treated with RAASis, and RAASi prescription was greater in stages 2–4 of CKD. Hyperkalemia occurred in 9.2% of RAASi-treated patients, and the adjusted rate of hyperkalemia among patients with stage 4–5 CKD was 3-fold higher compared with patients with eGFR > 60 ml/min/1.73 m Blood pressure lowering therapy has shown to prevent the onset of poor cardiovascular outcomes and delay the progression of kidney disease (Chronic kidney disease (CKD), defined as decrease in kidney function manifested as presence of structural or functional kidney abnormalities or estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 mSeveral randomized clinical trials have clearly shown that inhibition of the renin-angiotensin aldosterone system (RAAS) can reduce the risk of death and slow disease progression in patients with heart failure (HF), CKD, and diabetes –7. ThereHowever, the use of these drugs may be limited, since they can cause hyperkalemia  typical.Several recommendations for minimizing the risk of hyperkalemia have been provided by current treatment guidelines, including: avoiding RAASi therapy in patients at risk of hyperkalemia, discontinuing drugs that can interfere with renal potassium excretion before initiating RAAS inhibitors, titrating the dose of the RAASis, and performing regular monitoring of potassium serum levels –10. MoreTherefore, there is a substantial gap between recommendations in treatment guidelines and the real-world practice in the use of RAASis. This point is crucial, since discontinuation of RAASis after the onset of hyperkalemia may increases the risk of poor outcomes, with a combined deleterious effect of hyperkalemia and withdrawal of RAASi on prognosis .n = 238  or angiotensin II receptor blockers (ARBs)] during the study period, for whom at least 1 year of data during RAASi treatment was available.The study included all adult (≥ 18 years) patients presenting an estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 mWe excluded patients with (1) end-stage renal disease (ESRD) needing dialysis or kidney transplant at baseline (2) no qualifying eGFR measurement, (3) <6 follow-up visits in the study period, and (4) <1 year of observable time during RAASi therapy for renal replacement therapy initiation, loss to follow-up, or death.For each patient, the follow-up started at baseline (time of enrolment) and continued until the earliest transfer out of the practice, loss to follow-up, dialysis initiation, death, or end of the study period (December 2019).All the patients were evaluated according to the practice of our center, at baseline, and in follow-up visits at different times according to the degree of reduction in renal function. Age, sex, underlying cause of CKD, and comorbid conditions for all the patients were recorded during baseline visit. Baseline and follow-up visits included blood and urine sample tests , eGFR evaluation, clinical examination, vital sign measurements, and interviews for standardized questionnaires.2), while the CKD-EPI equation has demonstrated improved accuracy for eGFR levels > 60 ml/min/1.73 m2 .All laboratory values were measured by the automated, standardized methods used in our hospital. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation . The MDR/1.73 m2 . Therefo/1.73 m2 : > 90 (sThe study outcomes of interest include: (1) prevalence of patients with CKD treated with RAASis, and distribution of the use of RAASis in different CKD stages; (2) evaluation, in patients with CKD patients with RAASis , of the incidence of hyperkalemia; (3) proportion of patients with RAASi medication change  after experiencing incident hyperkalemia.The study was conducted in accordance with the principles outlined in the Declaration of Helsinki and was approved by a local ethics committee.An initial descriptive analysis was performed to investigate baseline characteristics of the study population, incidence of hyperkalemia, and changes in RAASi therapy. Categorical variables were presented as frequency distribution. Normally distributed data were presented as means and standard deviations, whereas non-normally distributed data were reported as median and interquartile range (IQR). Chi squared test was performed to detect differences among proportions. Analysis of variance (ANOVA) and Kruskal-Wallis test were performed to investigate differences in baseline characteristics among CKD stages for normally and non-normally distributed data, respectively.Post hoc analyses were performed by Tukey test and Dunn test for parametric and nonparametric data, respectively.We analyzed the variables at the time of discontinuation of RAASi and after 8, 16, 24, and 52 weeks . Statistical analyses were performed by ANOVA for normally distributed data and Friedman test for nonparametric data. Binary logistic regression was used to estimate the influence of type of RAASi, smoking status, diabetes, heart failure, CKD stage, and sex in modulating the risk of hyperkalemia.p-value was lower than 0.05. Statistical analysis was performed using R version 3.6.1 with R Studio version 1.2.5033.Differences were considered statistically significant when 2 (IQR 45.5), and median potassium level at baseline was 4.7 mmol/L (IQR.8).We identified 809 adult CKD responding to all inclusion criteria. Of these 809 patients, 556 (68.7%) had ≥ 1 RAASi prescription; thus they were eligible for the study . The maiThe prevalence of patients with CKD patients with RAASi was 68.7%; RAASis were equally distributed among stages 2, 3, and 4 . In partp < 0.0001). Of these 51 patients with hyperkalemia, 40 developed potassium serum levels between 5.1 and 5.5 mmol/L, eight patients between 5.6 and 6 mmol/L, two subjects between 6.6 and 7 mmol/L, and one patient > 7.1 mmol/L.A total of 51 patients with CKD treated with RAASis experienced an episode of hyperkalemia during the follow-up period  changed RAASi treatment prescription. Among these patients, 23 (74.2%) discontinued RAASi treatment, for one patient (3.2%) was prescribed a reduced dose of these agents, and seven (22.6%) reduced number of RAASi drugs, changing from combination of ACEi + ARB to monotherapy . No signIn binary logistic regression analysis, female sex vs. male and status of previous smoker or non-smoker vs. smoker represented protective factors for hyperkalemia. On the contrary, diabetes and CKD stages 3, 4, and 5 vs. stage 1 were found to be risk factors . The conFinally, no correlation was found between use of concomitant medications affecting potassium levels and development of hyperkalemia (data not shown).In our CKD-population-based cohort study, we observed an overall hyperkalemia incidence of 9.2% in over 556 patients with CKD s treated with RAASis, which did not significantly increase from stage 1 to 3, while it significantly augmented from stages 3 to 5.Among those who experienced incident hyperkalemia, most patients changed RAASi medication therapy  .Several articles have reported that RAASis are underutilized in patients with CKD, and that hyperkalemia is the major barrier for their initiation or sustained treatment. In a recent report of Shiriziad et al. that examined variables associated with prescription of renin-angiotensin system blockers in patients with CKD, the authors reported that 36% of patients with moderate to severe CKD and indication for RAASi therapy were not prescribed renin-angiotensin system blockade, and that the most common documented reasons were hyperkalemia and history of acute kidney injury . RAASi dIt is, therefore, important to determine the prevalence and risk factors of hyperkalemia secondary to RAASi therapy, and the relationship between hyperkalemia and treatment interruptions/cessations.2.Consistently with the results of the current literature, our study confirms that history of CKD (stages 3–5) is associated with elevated risk of hyperkalemia as well as with RAASi treatment modifications , 24. Ove2 (n = 346). In another article, a more recent study on 20,184 patients with CKD, 46.6% of them showed changes in their RAASi therapy (discontinuation: 36.6% and dose reduction: 10%)  . Our reson: 10%) –31. Receon: 10%) . Finallyon: 10%) . HoweverAs with any retrospective observational study, our study has some limitations that should be considered: at first, we could not select only new-user patients due to the impossibility to exactly define the start date of RAASi therapy already present at first visit. Moreover, we were limited in our ability to assess for possible temporary periods without being under RAASi therapy, for the analysis of sodium and potassium dietary intake, and for the use of concomitant medications including those known to affect potassium serum levels. Moreover, we do not have bicarbonate values for our patients, so we could not investigate for a possible correlation between hyperkalemia and metabolic acidosis, in particular for patients with eGFR < 30 ml/min. Finally, we did not include a “control” group of patients with CKD receiving other antihypertensive medications to compare outcomes or incidence of hyperkalemia.In conclusion, in this study on a large cohort of adults RAASi users with CKD, the incidence of hyperkalemia was frequently observed, and rates increased with worsening levels of renal function from stages 1 to 3. RAASi medication change following an episode of hyperkalemia occurred in almost half of the patients after experiencing hyperkalemia.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 Carlo Romano. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.AP had the original idea. ER, IC, MAn, MP, MR, and MAm took in care the patient. PB performed the statistic evaluation. AP, ER, and IC wrote the paper. All authors have read and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: The study aimed to assess the health-related quality of life (HRQoL) and its associated factors among urban slum dwellers who migrated from different rural parts of Bangladesh. Methods: The present study analyzed data from a Migration and Mobility Determinants on Health survey and was conducted in 2017 among 935 migrant slum dwellers of Dhaka city (North & South) and Gazipur City Corporations, as a part of the icddr,b’s Urban Health and Demographic Surveillance System (UHDSS). The face-to-face interviews were conducted with the adult population by using a semi-structured questionnaire that included variables related to socio-demographics, migration, occupation, and HRQoL (SF-12). Bivariate and multiple linear regression analyses were performed to determine the factors associated with HRQoL. Results: The mean (±SD) scores of physical component summary (PCS), and mental component summary (MCS) were 57.40 ± 22.73 and 60.77 ± 22.51, respectively. As per multiple regression analysis, lower PCS scores were associated with having older age, being female, and not having any job. Mean MCS scores were significantly lower among participants who reported having older age, not having any job, not working/ less working hours (≤8 h/day), as well as increased work-related stress in the current urban slum. Conclusions: The findings suggest that available urban social protection programs should include a comprehensive social safety net for the improvement of the slum infrastructure as well as proper health care and risk mitigation plans at workplaces. Globally, urban populations have, in absolute and relative terms, been growing for the past century, and the United Nations (UN) projects that the global urban population will increase by around 1.3 billion by 2030, while the rural population will essentially remain constant ,5. AlmosA rapid shift from an agrarian to an industrial economy and the concomitant creation of urban occupational opportunities have incentivized many individuals to migrate from rural to urban areas. This migration is not driven by jobs alone, and other contributing factors include natural disasters, economic stagnation, poverty, political and religious violence, and an expectation of a better life ,10,11,12HRQoL is a multidimensional construct that encompasses physical, mental, and social health dimensions . While aThere is rich global literature on the health of urban slum dwellers. Likewise, in Bangladesh, slightly more than half of all the health studies on urban slum dwellers focused on nutrition, maternal and child health, health care services delivery, and disease-specific incidence and prevalence. Neither in Bangladesh nor elsewhere in the developing world, does one tend to see studies measuring a more encompassing notion of health, such as HRQoL ,28,29,30A cross-sectional survey on the determinants of migration, mobility, and health in residents of urban slums in Dhaka (North & South) and Gazipur City Corporations was conducted in 2017. Data were drawn from an ongoing Urban Health and Demographic Surveillance System (UHDSS), which gathers information on basic demographic characteristics and events including birth, death, marriage, and divorce, migrations , household split, fertility regulation, as well as safe motherhood and newborn care practices . The pop2 and an approximate population of 2.5 million), Dhaka South City Corporation (located in the southern site with an area of 109.251 km2 and an approximate population of 12 million), and Gazipur City Corporation (situated in the southern zone with an area of 329.23 km2 and an approximate population of 2.5 million) [In Bangladesh, city corporations are the highest level of urban local governments and one of the country’s major urban focal points, with the most advanced administrative and technical capabilities. In the census of slum areas in 2014, a total of 13,938 slums were counted covering all cities and other urban areas of Bangladesh, out of which 33.62% were from Dhaka North (11.80%), Dhaka South (12.59%), and Gazipur (9.23%) City Corporations [million) ,32,33,34A total of 1100 adult residents aged 18 years of age or more  were randomly selected and interviewed from the UHDSS database. Of them, 935 subjects who had migrated to the current slum areas from their rural residence were included in the final analysis.Each interview relied on a semi-structured Bangla questionnaire including informed consent with sections on socio-demographic characteristics, migration history, and the SF-12 . The facSocio-demographic data included age, sex, marital status, and education from the existing database of the UHDSS. As part of the Migration and Mobility Determinants on Health survey, the participants were also asked about migration-related information about when they migrated and the reasons for migration.The participants were asked to compare their present status of living in urban slums with their former rural places of residence. Comparisons were made between housing environments, toilet facilities, water quality, and open space. They were explicitly asked whether their current residence was “worse”, “the same as before”, or “better” than their previous rural residence.Sources of income and working hours in current residence were asked during the survey. As slum dwellers are engaged in various risky occupations and have no defined working hours, we added two additional self-reported questions that measured the work-related risk and stress in the current place .The validated Bangla version of the SF-12 was used to assess the HRQoL ,37. The p < 0.25). Finally, multiple regression analyses were performed individually to model both PCS and MCS involving all candidate-independent variables selected from the bivariate regression analyses. In addition, Pearson product–moment correlations were estimated between the different subscales and domains of SF-12. A p-value less than 0.05 was considered significant for all statistical tests.Two statistical software packages were used to analyze and manage the data (IBM SPSS Statistics version 25 and STATA version 13). Data cleaning, coding, and sorting were performed using SPSS. Linear regression analyses were performed using STATA to model the total scores of PCS and MCS in both unadjusted and adjusted analyses. The bivariate regression analyses were used to determine the candidate-independent variables for inclusion in the multiple regression analyses  of the icddr,b that includes a Research Review Committee and an Ethics Review Committee.A total of 935 participants were included in the final analysis. Of them, more than half were females (54.2%), half of them had no formal education (51.0%), and most were married (89.7%) . The majWhen comparing their current living situations with their previous rural residence, 54.3% of participants reported a worse current housing environment, 58% reported a worse current water supply, and 83.4% reported worse housing space . In contr = 0.57; p < 0.001).p < 0.25). After statistical adjustment, participants’ age was negatively and significantly associated with PCS scores (p < 0.001); females had significantly lower mean PCS scores than males (p < 0.001); and all employment categories had lower mean PCS scores compared with the category “jobs” (p =< 0.001–0.009). Being divorced/widowed, having no education, longer duration of migration, and not working/ less working (≤8 h/day), were significantly (p < 0.05) associated with lower PCS scores in the bivariate analyses but were not significant in the multiple regression analysis.The bivariate regression analyses  identifip < 0.25). Of the candidate variables, after statistical adjustment, participants’ age was negatively and significantly associated with MCS scores (p < 0.001); employment category “daily wager and others” exhibited lower mean MCS scores compared with the category “jobs” (p = 0.031–0.004); those reporting currently not working or working for ≤ 8 h/day had lower mean MCS scores compared with those who worked for >8 h/days (p = 0.001–0.002); and those reporting increased work-related stress in the current residence had lower mean MCS scores than those who did not (p = 0.011). Being female, divorced/ widowed, longer duration of migration, and having no education were significantly (p < 0.05) associated with lower MCS scores in bivariate analysis, but they were not significant in the multiple regression analysis.The bivariate regression analyses  identifiDue to overcrowding, congestion, and lack of proper sanitation and water, underprivileged rural migrants in urban slums may experience poor HRQoL ,15. To dAmong the SF-12’s eight subscales, the highest mean score was found in the social functioning; in contrast, the general health perception subscale exhibited the lowest mean scores. The slum dwellers mostly live in a densely populated environment, so they are more likely to live as a close community with a greater rate of social interaction ,41. HencIn our study, the mean scores of PCS and MCS were 57.40 (SD = 22.73) and 60.77 (SD = 22.51), respectively. The mean scores of PCS and MCS were lower than a previous study conducted among Iraqi immigrants settled in Malaysia using the SF-36 instrument . In the In the current study, in terms of both PCS and MCS, the HRQoL was comparatively higher in participants who reported a shorter duration of time since migration (≤5 years), and the score became relatively lower with the longer duration of migration . However, the duration of migration was not significant in the multiple regression. Participants with older age were significantly associated with lower PCS and MCS scores. This can possibly be due to the fact that young migrants were more active about finding new opportunities and building a better life for the future ,49,50. EIn terms of both PCS and MCS, those who did not work at all (unemployed) exhibited lower mean scores. This is consistent with most studies looking at the relationship between wealth and health e.g., ,61,62). ,62. 61,6The mean PCS scores were significantly lower among female participants compared to among males (54.4 ± 22.63 vs. 60.95 ± 22.37), which is supported by other international studies conducted among migrants and/or slum dwellers in China, Germany, Iran, Italy, Kenya, and Thailand ,65,66,67p < 0.05) associated with lower PCS scores in bivariate analysis. Being female, being divorced/ widowed, longer duration of migration, and having no education were significantly (p < 0.05) associated with lower MCS scores in bivariate analysis. None of these factors were significant in the multiple regression analysis.Being divorced/widowed, having no education, longer duration of migration, and not working/ less working (≤8 h/day) were all significantly  live in different slum areas in Bangladesh, the immediate attention should be taken to improve their HRQoL with urban-friendly health policies and services to ensure improvement in overall urban health . MoreoveThe study has several limitations that should be acknowledged when interpreting the results. Firstly, the study was cross-sectional and did not permit any cause and effect relationship to be inferred. A prospective study would be helpful to determine sequential relationships. Furthermore, although the participants were recruited using random sampling, the sample is unlikely to be representative of the migrants to urban slums because the slums under the surveillance in the UHDSS were not randomly selected. Despite the fact that the SF-12 instrument has been validated with other populations in Bangladesh, it has not been separately validated in slum dwellers. In addition, following many studies conducted in low- and middle-income countries (LMICs), we used the SF-12 cutoff score as 50 as per the standard for the American general population, since no specialized scores for the developing countries were found ,47,73,74The findings suggest future research is needed in various urban settings including small towns and municipalities to obtain consolidated findings and compare health indicators across urban slum areas. The findings from this study can be enhanced by conducting in-depth qualitative investigations to elicit context-sensitive information to answer why and how the occupational issues or poor housing affecting the HRQoL of the urban poor. A more comprehensive study with prospective methods should be considered as part of any plan to improve the HRQoL among migrants dwelling in urban slum areas. To note, there is no standard SF-12 cutoff for urban poor people in LMICs. Thus, research about the psychometric characteristics along with cutoff point justification of the SF-12 among urban slum dwellers is also needed. This research would add to the body of knowledge by identifying important factors that contribute to the quality of life and well-being of low-income urban migrants. It is evident that migration stressors and occupational health hazards are the important determinants of health among these populations. Therefore, policy attention should be given to appropriately address these issues to improve the quality of life of the urban poor. While creating livelihood opportunities in rural areas is critical, the Government of Bangladesh needs to formulate and implement policies and programs to ensure access to quality and essential health services, improving housing and living conditions in urban slums. Consideration should also be given to occupational health and safety measures to reduce health risks in factories and other workplaces, including strengthening relevant laws and regulations to reduce health risks at the workplace .The present findings provide baseline information about the HRQoL of a sample of urban slum dwellers who migrated from different parts of Bangladesh. The poor HRQoL was observed among migrant slum dwellers, especially among elderly people, females, and migrated for longer duration. The findings suggest the need for evidence-based strategies to direct government policies in order to improve the HRQoL of low-income migrant populations. Available urban social protection programs should include a comprehensive social safety net for the improvement of the slum infrastructure as well as proper health care and risk mitigation plans at workplaces.


Although clinical studies have been carried out on the effects of weight reduction in sleep apnea patients, no direct link has been shown between weight reduction and changes in cardio-metabolic risk factors. We aimed to analyze changes in the apnea–hypopnea index and selected cardio-metabolic parameters  in relation to the reduction in body mass index in obstructive sleep apnea patients. Medline, Web of Science and Cochrane databases were searched to combine results from individual studies in a single meta-analysis. We identified 333 relevant articles, from which 30 papers were assigned for full-text review, and finally 10  were included for data analysis. One unit of body mass index reduction was found to significantly influence changes in the apnea–hypopnea index , total cholesterol , triglycerides , fasting insulin , systolic  and diastolic blood pressure . Practical application of lifestyle modification resulting in the reduction of one unit of body mass index gives meaningful changes in selected cardio-metabolic risk factors in obstructive sleep apnea patients. Obstructive sleep apnea (OSA) is a recognized cardio-metabolic disorder affecting 53% of the middle-to-older age general population, and 36% of OSA subjects having exclusive positional sleep apnea can be treated with positional therapy ,2. OSA iCurrently, continuous positive airway pressure (CPAP) therapy is the ‘gold standard’ treatment for OSA, with dietary interventions and physical activity promoting weight loss encouraged in obese OSA individuals . An incrBecause of this fact, we aimed this study to analyze changes in the AHI and selected cardio-metabolic parameters , triglycerides (TG), Glc, insulin, systolic and diastolic blood pressure ) in relation to reductions in the BMI in OSA patients.The databases Medline, Cochrane Library and Web of Knowledge were searched for clinical studies carried out between 1958 and November 2020 that reported the effect of lifestyle modification on BMI and selected cardio-metabolic parameters as primary or secondary outcomes in individuals with OSA.The search strategy was restricted to humans, English language and original articles. The search was based upon the following index terms and titles: #1, sleep or apnea or obstructive sleep apnea or obstructive sleep apnea or sleep-disordered breathing and #2, diet or dietary intervention or diet, fat-restricted or energy intake or energy reduction and #3, weight loss or weight and #4, insulin or insulin resistance or insulin-secreting cells or glucose or lipids or triglycerides or cholesterol, and not animals. The PRISMA Statement was followed .Only studies run with patients suffering from OSA indicating the changes in BMI, AHI and selected blood parameters after lifestyle modification were included. Intervention studies  were taken into consideration. The articles that did not meet inclusion criteria were excluded.Relevant articles were identified by screening the abstracts, titles and full texts. The study selection process was performed by two independent researchers in parallel for each database, cross-checked by a third reviewer. For each full-text paper, information was extracted including general information , study characteristics , characteristics of studied population , assessment methods  and type of outcome . The relationships between BMI reduction and AHI, TC, TG, Glc and insulin changes respectively were described as mean difference per 1 unit of BMI reduction if the effect of lifestyle modification was linked with reductions or increases in the analyzed parameters.To assess the study quality, the Cochrane risk of bias for RCTs was used. For NRS, a nine-point scoring system according to the Newcastle–Ottawa scale was applied , where aWhen possible, the recorded Glc, TC and TG concentrations were converted to mmol/L and insulin concentration to pmol/L in order to standardize the results. A meta-analysis was performed to combine the results of the individual studies. Data were analyzed using a random-effects model, which allowed for true effect variation between studies. The effect size of a study was investigated by calculating mean difference per unit of BMI reduction (treated as an objective measurement of body weight change) with a 95% confidence interval.The heterogeneity of the sum of studies was tested for significance. As a measure for quantifying inconsistencies, I2 was selected . The resWe initially identified 333 potentially relevant publications from which, after title search, 97 articles were included. After duplicate removal, 30 papers were assigned for full-text review and finally 10 articles were included for data extraction and analysis ,22,23,242, a mean age of 35–70 [The characteristics of clinical studies (randomized and nonrandomized) and populations are presented in of 35–70  and a prof 35–70  to 24 weof 35–70 , based oof 35–70 ,22,23,24The dietary strategies leading to a decrease in energy intake were based on a reduced intake of fat or general caloric restriction ,22,23,24p < 0.00001, I2 = 95%)  .For each study, the square represents the point estimate of the effect. Horizontal lines join lower and upper limits of the 95% CI of this effect. The area of shaded squares reflects the relative weight of the study in the meta-analysis. Diamonds represent the subgroup mean difference and pooled mean differences. CI indicates the confidence interval (upper and lower limit) ,22,23,24Details about the analyzed biomarkers, at baseline and at the end of the intervention, or mean differences between the concentrations, were reported in only six studies ,16,17,24Mean decreases ranged from 0.26 mmol/L  to 0.67 p = 0.03, I2 = 0%), TG  and fasting insulin   and DBP   , as well2 = 90%) .For each study, the square represents the point estimate of the effect. Horizontal lines join lower and upper limits of the 95% CI of this effect. The area of shaded squares reflects the relative weight of the study in the meta-analysis. Diamonds represent the subgroup mean difference and pooled mean differences. CI indicates the confidence interval (upper and lower limit) ,16,17,24p > 0.05)—in some cases, due to the limited number of studies, analysis was not possible . Nevertheless, none of the subgroup analyses, with regards to AHI changes and cardio-metabolic risk factors, indicated significance .2 [p < 0.0001). These data are similar to those published on the OSA group of patients. For example, de Melo et al. [p < 0.001). It was also confirmed that a long-term lifestyle modification program could be more effective in reducing BMI  in comparison to the usual care of OSA patients  [It was imperative for the conducted review to show that OSA patients should be recognized as the core group with a prime interest in changing diet being the determinant of “metabolic health”. However, only limited data are available with regards to dietary behaviors in OSA. It has to be highlighted that lifestyle change is very unlikely in this group of patients; therefore, the likelihood of the positive effect in OSA patients could be even smaller. It has been shown by Fogelholm et al.  that pat2 . Increas2 ,27. For 2 , sustain2 . In clin2 ,30. We d2 . A diet 2 , based oo et al.  has show< 0.001) .The prevalence of cardiovascular diseases is increased in patients with OSA, possibly related to dyslipidemia in these individuals . The finDespite an increasing number of dietary intervention studies, the body of evidence remains limited by either small sample size (an inclusion-only arm of intervention without use of devices) or inclusion of nonrandomized trials and studies with behavioral support. Only future clinical trials with long-term follow-up periods can address this limitation. Moreover, no information on possible comorbidities of individuals in the analyzed studies was provided, which could also influence obtained data. Furthermore, the present findings are based on limited ethnicity (Caucasian); therefore, results could vary as a function of ethnic background. Although, the duration of the interventions in analyzed studies was relatively long (up to 24 weeks), we could observe long-term follow-up changes of analyzed cardio-metabolic parameters in a few studies. We did not analyze interventions based on physical activity, which is commonly recommended to OSA patients with standard therapy and applied as a pragmatic strategy (hard to accept by patients having stable behavior habits), though alone it does not provide significant clinical benefits . It mustIn conclusion, we find that lifestyle modification resulting in the reduction of one unit of BMI gives meaningful and positive changes in selected cardio-metabolic risk factors such as TC, TG, fasting insulin and BP in OSA patients. Broader interventional studies are needed to assess different dietary approaches in OSA individuals.


Thymus vulgaris (Lamiaceae) essential oil (EO) was investigated in order to evaluate its biological properties against microorganisms affecting two Tholu Bommalu, typical Indian leather puppets stored at the International Puppets Museum “Antonio Pasqualino” of Palermo, Italy. A GC–MS analysis, using both polar and apolar columns, was used to determine the chemical composition of the essential oil. The aim of this study was to evaluate the antimicrobial effectiveness of the Thymus vulgaris and Crithmum maritimum essential oils in vapor phase to disinfect heritage leather puppets. Pieces of leather artifacts that were affected by different bacterial colonies were exposed to EO under vacuum and static evaporation conditions. The results presented showed that the vaporization of essential oil was an efficient method in the disinfection of natural skins, eradicating microorganism in short times. T. vulgaris EO in the 50% solution showed excellent inhibitory activity against isolated bacteria with both methods, but the obtained results suggest that the vacuum method allowed for faster exposition of the artifacts to the biocide. Furthermore, the biocidal properties of the essential oil of a Sicilian accession of Crithmum maritimum (Apiaceae) aerial parts were compared and investigated. The results of the latter essential oil showed a poor activity against the isolated micro-organisms.The chemical profile of the  Biodeterioration of cultural heritage causes different alteration processes affecting the constitutive materials of artworks. In particular, fungi and bacteria are able to colonize different artworks comprised of natural materials through aerosol pollution, representing complex problems for conservation by causing a loss of mechanic resistance and deterioration of pictorial layers. Moreover, inadequate exposure to specific thermo-hygrometric parameters can increase the concentrations of microbial colonies, enhancing the deterioration process. For the purpose of inhibiting the biological colonization, different chemical biocides, such as permethrin or/and benzalkonium chloride (BAK), are frequently used. These products are usually toxic for humans and the environment. Hence, in the last decade, essential oils have been applied in order to combat cultural heritage biodeterioration as an eco-friendly solution ,10,11,12However, the disinfection process by using volatile compounds, such essential oils (EOs), can require a long time, so the purpose of this work was to find a way to accelerate this. During the evaporation process of a specific liquid, the number of molecules escaping from the liquid increases every second and those that condense back into the liquid also increase. Reaching thermodynamic equilibrium, the vapor phase exerts a pressure on its condensed phase, which is called “vapor pressure” . The speThymus vulgaris L. (Lamiaceae) and Crithmum maritimum L. (Apiaceae).To investigate a suitable alternative to traditional synthetic biocides, we decided to analyze the biocidal properties of two different essential oils: Thymus EO was selected due to its microbial properties, which have previously been reported in several studies [Thymus vulgaris essential oil has been shown to be quite effective against several microorganisms [ studies ,19,20,21rganisms ,23.Crithmum maritimum has been largely investigated [Candida albicans, Cryptococcus neoformans and several dermatophytes and Aspergillus spp has been demonstrated.In addition, the essential oil of stigated . Its antstigated ,26, showThymus essential oil for leather disinfection to date. Thus, the main purpose of this study was to undertake the first study of the application of the Thymus essential oil to heritage leather disinfection under a vacuum system. Consequently, in the context of our ongoing research on endemic Sicilian plants [Thymus demonstrated in the aforementioned articles, we decided to utilize the EO of Thymus vulgaris as natural biocide against bacteria affecting two Tholu Bommalu, typical Indian leather puppets, which were stored at the International Puppets Museum “Antonio Pasqualino”. We exploited the high vacuum inside ad hoc chambers in order to speed up the disinfection process. The activity of the essential oil of T. vulgaris was then compared with that of Sicilian Crithmum maritimum EO. These results were compared with the results of using a conventional synthetic biocide, benzalkonium chloride, as a disinfectant.There are no reports on the use of n plants ,28,29 ann plants ,31,32, aThymus vulgaris was analyzed by GC-MS analysis and is reported in p-cymene as the most abundant compound (35.96%), followed by terpinen-4-ol (10.29%) and α-terpinene (8.85%). Oxygenated monoterpenes are also dominant (43.67%) with thymol (25.38%). In contrast, sesquiterpene hydrocarbons accounted for only 4.34%; no oxygenated sesquiterpenes were identified in the chromatogram of the EO. Comparing different samples of T. vulgaris from Saudi Arabia [p-cymene and α-terpineol but also in camphene and caryophyllene.The chemical composition of the essential oil of i Arabia  and Frani Arabia  to our rCrithmum maritimum was analyzed by GC-MS analysis and is reported in β-myrcene as the most abundant compound (13.66%), followed by p-cymene (11.67%) and β-phellandrene (6.57%). Oxygenated monoterpenes are also dominant (40.03%) with thymol acetate (14.38%). In contrast, hydrocarbon and oxygenated sesquiterpenes accounted for only 1.94% and 0.50%, respectively.The chemical composition of the essential oil obtained from T. vulgaris and C. maritimum EOs against bacteria species isolated from Tholu Bommalu, an agar disk diffusion method (ADD) was performed , which were able to produce inhibition halos of up to 33 mm. In contrast, the C. maritimum essential oil did not show inhibition halos, except in the case of Bacillus sp., although these inhibition halos were smaller than those of T. vulgaris.In order to test the antimicrobial activity of T. vulgaris EO was displayed against all isolated colonies and clearly had a greater effect than that of the controls , the reference biocide, and pentane, as shown in C. maritimum EO, which produced inhibition halos smaller than those produced by the controls.The antimicrobial activity of the T. vulgaris EO are in agreement with its chemical composition. Several studies highlighted how EOs rich in phenolic compounds, such as thymol or carvacrol, have a strong antimicrobial activity. In particular, thymol seems to be bioactive against more than twelve different bacterial colonies [The biocide properties of the colonies ,42.Tholu Bommalu and the fragility of the parchment support, the aim was to find a disinfection process that was minimally invasive but also fast, allowing replicability in the future for the entire collection of Indian shadow puppets stored in the International Puppets Museum, “Antonio Pasqualino”.Considering the huge presence of microbial colonies on Thymus vulgaris EO, under both normal evaporation conditions and under vacuum inside a Plexiglas chamber  and Sabouraud dextrose agar . Nutrient agar supports a wide range of microorganisms, whereas Sabouraud is mainly used to cultivate fungi or filamentous bacteria.Microbial in vitro cultures were performed on both nutrient agar , evaluating parameters such as total color differences (ΔE), a * (red-green), L * (lightness) and b * (yellow-blue) before and after the EO treatment.Furthermore, to avoid discomfort and residual odor of the same on the artifact, the latter was subjected to three high vacuum cycles, maintaining stable thermo-hygrometric parameters, in order to eliminate the possible presence of some volatile components of the essential oil.Thymus vulgaris  was purchased from Authentic Oil Co, Unit 1, Little Castle Farm, Raglan, Monmouthshire, NP15 2BX, UK. In this case, the aerial parts of T. vulgaris come from Daran, Karaman, Turkey.The essential oil of Crithmum maritimum were collected in Addaura (Mondello), Palermo, Sicily, Italy , in June 2020 and a voucher specimen was deposited in STEBICEF Department, University of Palermo (PAL 348/20).The aerial parts of C. maritimum were subjected to hydrodistillation for 3 h using Clevenger’s apparatus [v/w)) was dried with anhydrous sodium sulfate, filtered and stored in a freezer at −20 °C until the time of analyses.A quantity of 300 g of the aerial parts of pparatus . The oil−1). The injector and detector temperatures were set at 250 °C and 290 °C, respectively. An amount of 1 μL of each oil solution (3% EO/hexane v/v) was injected with a split mode. Linear retention indices (LRI) were determined by using retention times of n-alkanes (C8-C40), and the peaks were identified by comparison with mass spectra and by comparison to their relative retention indices with WILEY275 (Wiley), NIST 17 , ADAMS  and FFNSC2  libraries.Analyses of essential oils were performed according to the procedure reported by Rigano et al. . EO analv/v) , the reference biocide, and pentane , the solvent accounting for fifty percentage of the EO solution, were controls used in agar disc diffusion (ADD) assays [Benzalkonium chloride (3% ) assays ,46. ADD Tholu Bommalu was sampled by sterile stubs. Distinctive colonies, in morphology and/or pigmentation, were isolated on the nutrient agar in vitro culture. Taxonomical identification was performed by molecular analysis of the 16S rDNA gene or ITS1-2 containing DNA region [Bacillus sp., Georgenia sp., Ornithinibacillus sp. and Streptomyces sp. were identified as the prevalent genera (Gram + bacteria).Microbial patina on the leather substrata of A region . SpecifiT. vulgaris essential oil (100% or 50%) or control solutions  was leaned on the agar medium (9 cm Petri dishes) surface. Due to the non-miscibility of essential oils in water, fifty percent of the EO solution was composed of pentane. After incubation at 30 °C for 24 h, inhibition halos (i.hs.) differing in diameter (mm) were revealed, reflecting the antimicrobial activity and categorized as a sensitive strain (i.h. > 9 mm) or a resistant strain (i.h. < 9 mm). Georgenia sp. colonies were the most susceptible isolated bacteria, showing a relevant sensitivity to the essential oil with an inhibition zone of up to 18 mm. At the other end of the spectrum, Bacillus sp. was the most resistant with an i.h. of 14–17 mm diameters. The ADD in vitro method was performed to evaluate the antibacterial activity of EO and BAK solutions. An amount of 10 µL of each bacterial broth culture  was uniformly spread using a sterile Drigalsky spatula on the nutrient agar surface, and the surface was allowed to dry (1 h at 30 °C). A sterile paper disc  imbibed with 10 µL of the 2 was placed inside the vacuum system. In addition, the chamber was filled with the Thymus vulgaris EO, calculating the right amount to saturate atmosphere using the equation of a perfect gas; a thermo-hygrometer; and the leather samples, placed on a reticulated support made of cardboard and nylon to allow the volatile compounds to easily reach all points of the samples. To create vacuum, a diaphragm vacuum pump  was connected by a tube to the top of the chamber and was kept running for about one minute and then disconnected.In order to maintain stable thermo-hygrometric parameters , a saturated solution of MgClThymus vulgaris and Crithmum maritimum essential oils. The essential oil of T. vulgaris was characterized by a large presence of monoterpenes, p-cymene (35.96%), terpinen-4-ol (10.29%), α-terpinene (8.85%) and thymol (25.38%), while C. maritimum essential oil was dominated by β-myrcene (13.66%), followed by p-cymene (11.67%), β-phellandrene (6.57%) and thymol acetate (14.38%). In addition, we suggested an integrated approach to the most common disinfection processes, by using a vacuum chamber in order to allow the mechanism to act faster than usual. Thymus oil, in vapor phase, is a strong inhibitor for bacterial growth; every bacterial colony isolated showed significant sensitivity to both EO solutions  and was able to produce inhibition halos up to 33 mm. All colonies under vacuum conditions were significantly reduced compared to the same ones exposed to environmental conditions. In contrast, the C. maritimum essential oil did not show inhibition halos. The potential use of commercial plant essential oils, together with the achievements reached during the in vitro and in situ applications to control the growth of bacterial taxa, led us to hypothesize their use as natural biocides, replacing the most common toxic biocide usually used in the conservation of cultural heritage.The present work focused on determining the yield, the chemical composition and antimicrobial properties of


Kip1 is a gatekeeper of G1/S transition. It also regulates G2/M progression and cytokinesis completion, via CDK-dependent or -independent mechanisms. Recently, other important p27Kip1 functions have been described, including the regulation of cell motility and migration, the control of cell differentiation program and the activation of apoptosis/autophagy. Several factors modulate p27Kip1 activities, including its level, cellular localization and post-translational modifications. As a matter of fact, the protein is phosphorylated, ubiquitinated, SUMOylated, O-linked N-acetylglicosylated and acetylated on different residues. p27Kip1 belongs to the family of the intrinsically unstructured proteins and thus it is endowed with a large flexibility and numerous interactors, only partially identified. In this review, we look at p27Kip1 properties and ascribe part of its heterogeneous functions to the ability to act as an anchor or scaffold capable to participate in the construction of different platforms for modulating cell response to extracellular signals and allowing adaptation to environmental changes. The Cyclin-dependent kinase (CDK) regulator p27 Different disciplines, like Mathematics, Biology, Genetics, Fundamental Physics, Astronomy and Philosophy, have pointed out the advantage of chaos as opposed to the Newtonian cosmos with its deterministic and linear order ,2,3. IndTo date, many methods, including complex bioinformatic assessments, confirm that the lack of stable protein organization is an intrinsic property of the proteome, with its levels increasing during evolution (>40% of the proteome in Eukarya branches) . On thesAn extensive structural plasticity has also been observed in Scaffold Proteins (SPs)  that play important roles in numerous cellular processes. Mostly, these proteins employ their modular structured domains, often in combination with the regions that do not assume stable secondary structures . In the Kip1 , a key cell cycle modulator and a well-recognized IUP, might be also envisioned as an SP.In the following, we aim to discuss experimental proofs sustaining the view that p27p27 has been initially identified as a Cyclin-dependent kinase (CDK) inhibitor belonging to the CIP/Kip (Cyclin Inhibitory Protein/Kinase inhibitory protein) family. It plays fundamental roles in all phases of the cell division cycle. p27 is indeed a master regulator of G1 progression and G1→S transition and takes part in the control of G2 advancement and M phase/cytokinesis completion ,18,19,20Mechanistically, the protein inhibits Cyclin E(A)/CDK2 and Cyclin A(B)/CDK1 by forming inactive ternary complexes and assists the physically assembling of Cyclin Ds and CDK4/6 heterodimers ,21,22,2310-helix. p27 is tethered to CDK2, producing a hybrid p27/CDK2 beta-sheet, with 310-helix allocating into the catalytic cleft to block ATP access and, then, to inhibit the kinase. Through NMR analysis [10-helix disrupts the inhibitory conformation of the hybrid beta-sheet. This allows structural changes in CDK2 to reestablish specific interfacial contacts with Cyclin A as in the active Cyclin A/CDK2 binary complex. Subsequently, the ejection of the 310-helix is favored and the catalytic cleft of CDK2 becomes structurally very similar to that of the active Cyclin A/phospho-CDK2 complex. This is then able to lodge the ATP molecule as efficiently as the active holoenzyme, even without (Thr160) CDK2 phosphorylation carried out by CAK for the classical full activation [p27 has been one of the first IUPs whose mechanism of folding upon the binding has been characterized in detail. As matter of facts, biophysical and biochemical studies have allowed one to obtain a short but detailed movie that effectively showed the docking of the p27 N-terminal domain (including the kinase inhibitory domain or KID) on the Cyclin A/CDK2 heterodimer, characterizing the protein regions that bind, separately and sequentially, Cyclin A and CDK2 . Preciseanalysis  and moleanalysis , the pretivation ,26.CIP1/Waf1 and p57Kip2 , frequently, but nonexclusively, phosphorylation. The p27 unfolded state provides, like almost all IUPs, a very efficient housing for numerous PTMs. The importance of p27 PTMs has been evidenced in almost all functions and interactions as well as in the control of p27 localization, stability and degradation ,29, thusCells elaborate extracellular stimuli organizing an adaptive phenotype as an adequate response. This is necessary for the survival of living organisms . The theBy using a similar strategy, p27 controls PI3K/AKT signaling by modulating its phosphorylated status. Growth-factor-induced PI3K activation results in phosphatidylinositol-3,4,5-triphosphate production, recruitment of AKT to the plasma membrane and subsequent AKT activation by two post-translational modifications. PDK1 and TORC-2 complex phosphorylate AKT, respectively, on T308  and on SIn summary, by acting either on CDKs or on CDK-independent transduction pathways, p27 is a general cell phenotype modulator, although not all mechanistic details of its actions have been clarified. p27 modular structure and the folding upon binding also suggest that this protein might be an anchor for different proteins (or protein complexes) and that this feature might help in explaining some of its still unclarified cellular activities.Numerous pieces of evidence demonstrate that p27 is not simply a growth modulator. This activity might represent only one of the protein functions and probably additional roles still await to be identified. Mechanistically, a number of studies suggest that p27 could be envisioned as an SP favoring the interaction/modulation of additional proteins. The most straightforward example is its role in the assembly of early G1-Cyclin D/CDK complexes. Furthermore, in additional cases, p27 can be seen as a molecular platform for the recruitment of signaling proteins or enzymes involved in the bidirectional control of cellular processes. Following, we will show some instances suggestive of this view.−/− MEFs, showed that Cyclin Ds are quickly degraded and that the p27 reintroduction reversed the enhanced Cyclin D proteolysis and, in turn, induced the stabilization of Cyclin D/Cdk4 in ternary complexes [p27 was identified as a Cyclin E/CDK2 interactor and inhibitor in TGF-beta arrested mouse epithelial cells . Later oomplexes .Subsequently, Larrea and coworkers (2008) evidenced the p27 PTMs importance in these processes, confirming the relevance of PTMs in gaining scaffolding properties . Like a Referring to the relations of p27 with Cyclin/CDK complexes, in addition to the mechanism of interaction of p27 with Cyclin A/CDK2 elucidated in detail  including R194 is a better substrate of CyclinA/CDK2 than a similar peptide with alanine in 194 position . Thus, fBy virtue of its ability to control CDK interactors and CDK-containing complex formation, p27 also contributes significantly to neuronal apoptosis in response to neurotoxic agents, such as amyloid peptide Aβ(1–42) C. Many sFocusing on its ability to establish distinct relationships with Cyclin and CDK partners, we could appreciate the exquisite p27 promiscuity in the pathogenesis of Primary Effusion Lymphoma (PEL) related to the Kaposi Sarcoma-Associated Herpesvirus (KSHV) infection. This oncogenic γ2-herpesvirus is considered as a carcinogen of class I by the World Health Organization for the high number of viral products that mimic human proteins, such as v-Cyclin, a viral cyclin homolog showing an elevated homology with human Cyclin D2. v-Cyclin binds to several CDKs and its interaction with CDK6 contributes to the pathological function . It has Besides being a CDK regulator, p27 has been straightforwardly demonstrated to exert important roles in controlling cytoskeleton assembly/disassembly and cell movement. However, although the importance of the protein in these phenomena is functionally well established, the mechanistic details of p27 activity and its precise interactors do not appear definitely identified.Three major classes of elements, differing in size and in protein composition, work together to form a cytoskeleton of eukaryotic cells . Differe−/− MEFs and suggested a molecular mechanism by which p27 regulates cell movement affecting activation of RhoA, thus enhancing the activity of several kinases strongly involved in cytoskeleton dynamics and cell motility [The initial indication that cytoplasmic p27 controls actin cytoskeleton affecting cell migration derives from the seminal study by Dowdy’s group published in 1998 . The autmotility . One tarmotility ,68.According to the Besson’s study, p27 is able to block the binding of RhoA to its activators, the Rho–GEFs (Guanine nucleotide exchange factors) decreasing the accumulation of RhoA-GTP A. This iFocusing on the numerous additional aspects of the relationship between p27 and cytoskeletal dynamics, it is important to report its role in the regulation of neuronal migration and neurite branching, all mechanisms that entail actin and microtubule (MT) cytoskeleton remodeling. In this scenario, tubulin acetylation/deacetylation equilibrium is the protagonist, because it doses the molecular motors associated with microtubules and defines the velocity of organelle, protein or vesicle transport. Precisely, microtubule deacetylation causes locomotor deficits and disturbs MT-based axonal transport and neuronal connectivity ,72. SincDuring neurogenesis, cell cycle exit, cell migration and neuronal differentiation must be harmonized and, apparently, they are linked by p27 activities played in proliferation control ,77, MTs’In summary, these data suggest the possibility that p27 can mostly work as an efficient scaffold macromolecule that allows not only the remodeling/interplay of the numerous cytoskeleton components but also that permits an exchange of functional information/regulation between cell division cycle machinery and cytoskeleton dynamics. As a matter of fact, MTs and actin filaments are intersected not only for cell motility, defining degree and direction, but also for cell polarity definition. This is of pivotal relevance in orienting cell migration and cell division in developing tissues. This modulation appears of particular importance during embryogenesis and neurogenesis, to form an organized and coherent pluricellular structure . AdditioIt is interesting that p27 has also been reported to be a binding partner of an additional protein involved in MTs remodeling, namely, Protein Regulator of Cytokinesis 1 (PRC1). PRC1 is able to cross-link antiparallel MTs and plays a key role in central spindle formation. p27 interferes with the activity of PRC1 to bind MTs, thus hampering the increased MT bundling due to PRC1 overexpression .Two further components of the complex relationship between p27 and cell movement should be taken into consideration, namely, the interaction at cytosolic level of the protein with the MT-destabilizing protein stathmin and the ability of the protein to bind cortactin. In the first instance, p27 interferes with the stathmin capability to modulate MTs during the interphase, hampering their remodeling. In this case, p27 appears to reduce cell movement . In the d) has been investigated in details (p27/RhoA) and the results have suggested that the interaction is probably indirect. The same probably occurs in other cases, and p27 might represent an SP that allows complex interactions. It is to be underlined that several of the proteins reported above as p27 interactors are also able to interact with each other, suggesting the formation of dynamic complexes able to rapidly change their compositions/function similarly to DNA interacting complexes. Thus, although the relevance of p27 in cytoskeleton dynamics and function has been widely confirmed, additional structural/functional studies appear absolutely compulsory to shed light on this complex scenario. In In summary, p27 appears to interact with numerous distinct cytoskeleton-correlated proteins, RhoA, p115-GEF, PRC1, Citron-K, αTAT1, RSK1, cortactin and stathmin. In only one case, the binding affinity . By impeding the RAGULATOR complex formation, p27 also hinders the recruitment and consequent activation of key GTPases such as Rag and Rheb (the latter acting on MTORC1 for its full activation). Remarkably, this GTPase-targeting activity seems a general mechanism of action of cytoplasmic p27 in affecting cytoskeleton dynamics, organelle and vesicle movement, autophagy and cell motility.When p27 binds to LAMTOR1, it impedes the scaffold activity of the protein in building the RAGULATOR complex, thereby affecting negatively mTORC1 activity. This also determines that the transcription factor TFEB, which is normally phosphorylated by mTOR (the kinase component of MTORC1) and sequestered in the cytoplasm, is freed of translocating into the nucleus, stimulating transcription of several genes involved in autophagy and lysosome recycling. In this molecular mechanism, although p27 does not act as a classical scaffold, it interacts directly with the lysosome SP LAMTOR1, hampering its activity and affecting the formation of a highly structured complex. On the other hand, we cannot exclude that p27-LAMTOR1 interaction might represent the initial base of an alternative complex still uncharacterized. In this scenario, it may be interesting to underline that p27 binding affects the GAP (GTPase activating proteins) activities of LAMTOR1, previously identified as p27RF-Rho  in numerous human diseases, mainly in human cancers. The first observation of a possible role of p27 in cancerogenesis stems from a seminal study on mice ablated of the n1b gene . These gn1b gene . Furtheradiation . Some yeled MENX . Pellega animals . The fin altered . Moreove altered . CDKN1B ter BRAF . Finallyter BRAF ,105,106  altered . All theCDKN1B was demonstrated to improve cardiac function in mice post-myocardial infarction [p27 alterations have also been demonstrated in a specific condition associated with human diseases. Indeed, in endometriosis, p27 appears significantly reduced, and in congenital eye alteration, p27 post-synthetic changes have been demonstrated ,109. Hapfarction . Finallyfarction . Based oIn the development of novel pharmacological therapies, among the properties that an ideal drug should have, a high selectivity is certainly of fundamental importance. Therefore, the plasticity of IUPs and their large number of interactors would suggest that these proteins might not be therapeutic targets. This view is also supported by the obligatory absence/scarcity of IUPs crystallographic data that, conversely, are of great relevance in drug design . Recently, however, several different studies have demonstrated that an unfolded protein or unfolded protein region might be targetable for therapy . For exaA recent study by Kriwaki’s group reported the possibility of affecting the binding of p27 with other proteins . The stuWhy are these studies promising? Since p27 might be considered in some instances an SP, the Kriwaki study suggests that proteins facilitating the formation of complexes, albeit unstructured, might be the target of therapy, allowing the conclusion that the knowledge of the region involved in specific binding, even if part of IUP, might be considered for efficacious therapy. Obviously, their relevance depends on a detailed knowledge of interactors of the protein region to be targetable. A further aspect should be underlined. p27 decreased level, cellular mislocalization and structural changes due to mutations are all events correlated with human diseases. In this context, the ability of the protein to form different complexes acting as anchor should be investigated to unveil more comprehensive pathogenic mechanisms and to develop more efficacious therapeutic approaches. As frequently in Science, although much is known, the complete picture remains to be understood. Accordingly, in our view, the importance of randomness in biological and clinical phenomena must never be forgotten.


The Brazilian Cerrado is a highland tropical savanna considered a biodiversity hotspot with many endemic species of plants and animals. Over the years, most of the native areas of this biome became arable areas, and with inadequate management, some are nowadays at varying levels of degradation stage. Crop-livestock integrated systems (CLIS) are one option for the recovery of areas in degradation, improving the physicochemical and biological characteristics of the soil while increasing income and mitigating risks due to product diversification. Little is known about the effect of CLIS on the soil microbial community. Therefore, we perform this pilot case study to support further research on recovering degraded areas. The bacterial and fungal soil communities in the area with CLIS were compared to an area under moderate recovery (low-input recovering - LI) and native savanna (NS) area. Bacterial and fungal communities were investigated by 16S and ITS rRNA gene sequencing (deep rRNA sequencing). Ktedonobacteraceae and AD3 families were found predominantly in LI, confirming the relationship of the members of the Chloroflexi phylum in challenging environmental conditions, which can be evidenced in LI. The CLIS soil presented 63 exclusive bacterial families that were not found in LI or NS and presented a higher bacterial richness, which can be related to good land management. The NS area shared 21 and 6 families with CLIS and LI, respectively, suggesting that the intervention method used in the analyzed period brings microbial diversity closer to the conditions of the native area, demonstrating a trend of approximation between NS and CLIS even in the short term. The most abundant fungal phylum in NS treatment was Basidiomycota and Mucoromycota, whereas Ascomycota predominated in CLIS and LI. The fungal community needs more time to recover and to approximate from the native area than the bacterial community. However, according to the analysis of bacteria, the CLIS area behaved differently from the LI area, showing that this treatment induces a faster response to the increase in species richness, tending to more accelerated recovery. Results obtained herein encourage CLIS as a sustainable alternative for recovery and production in degraded areas. The climate of the region is marked by high temperatures and long periods of drought. The soils are naturally acidic, poor in nutrients, and rich in aluminum, with tropical savanna vegetation and distinct physiognomies ranging from pastures to forests . The mosasslands . The “Ce0% cover .Despite being considered a global hotspot of biodiversity, approximately 50% of the Cerrado native areas have been transformed into mechanized agriculture, forestry, and intensive livestock areas over the years . The inaThe crop-livestock integrated system (CLIS) involves intercropping, crop rotation, and succession with livestock grazing in the same area. This system aims to improve agricultural productivity and recover degraded land, due to improvements in soil physical, chemical, and biological characteristics . CLIS enOther recovering strategies propose minor soil interventions with lower inputs , taking more time to reach the full recovery of the area. These strategies could preserve soil biological content, which would help in the recovering process.Microorganisms are essential for soil productivity and fertility because they perform several important functions, such as decomposition of organic matter, nutrient solubilization, and cycling, and synthesis of phytohormones and antimicrobial compounds, thus promoting plant growth and protection . DiffereThere are several studies reporting changes in the microbial diversity in Brazilian Cerrado soil due to land use transformations . StudiesThus, the objective of this pilot case study was to evaluate the short-term effects of recovering degraded areas in the composition and structure of soil bacterial and fungal communities. The present study evaluated this soil biological condition in fields under recovery through CLIS and under a moderate intervention recovering comparing to native vegetation in the Brazilian savanna (Cerrado).The study was conducted at the “Boa Esperança” Teaching, Research, and Extension Unit  of the Institutional Project for Integrated Agricultural Production Systems of the Goiano Federal Institute (IF GOIANO) located in Iporá city, state of Goiás, Brazil . The soi1.The climate of the region is classified as tropical savanna , being 24.7°C the annual average temperature and 1,369 mm the rainfall average. The dry season is from May to September (winter) and the rainfall average is 62 mm. The rainy season is from October to April (summer) and the rainfall average is 1,307 mmThree areas with different land use strategies were evaluated: (a) recovery of an area in degradation via CLIS, (b) recovery of an area in degradation using a moderate intervention strategy , and (c) native Cerrado control area .–1 of dolomitic limestone , and 4.00 Mg.ha–1 of poultry litter applied on the surface. After, chisel plow at 0.25 m depth and 0.6 m spacing was applied. The remaining plants in the area (predominantly Urochloa brizantha and Urochloa humidicola) were desiccated with 1,440 g of glyphosate.ha–1. Seven days after desiccation, a triple intercropping with corn (Zea mays cv. “AG1051”), pigeon pea (Cajanus cajan cv. “Super N”), and Tamani grass (Megathyrsus maximus cv. “BRS Tamani”) were simultaneously sowed. The sowing was made with a 5-row mechanical seed drill using three maize rows intercalated with two pigeon pea rows. An additional fine seeds distribution system in the same machine sowed Tamani grass (5 kg of pure viable seeds.ha–1). The pigeon pea had a final population of 28,250 plants.ha–1 and maize had 67,000 plants.ha–1. The fertilization used was 200 kg.ha–1 of 8-41-5 (nitrogen-phosphorus-potassium). Topdressing fertilizations with N were performed in the corn vegetative stages of two (V2) and four (V4) fully expanded true leaves using 46 kg.ha–1 of N (100 kg.ha–1 of urea) in each operation.The CLIS field received 1.8 Mg.ha2. The material was ground and homogenized, then ensiled in micro-silos  for anaerobic fermentation. After 60 days, the micro-silos were opened, and the material was dried at 65°C by 72 h. The dry matter (DM) content was determined, and the DM yield per hectare was calculated. The dry material was grounded in a 1-mm Wiley mill to determine the levels of calcium (Ca), phosphorus (P), crude protein (CP), crude fiber (CF), ether extract (EE), mineral matter (MM), total digestible nutrients (TDN), acid detergent fiber (ADF), and neutral detergent fiber (NDF) (The intercropped forage was harvested for silage production in February 2018 (90 days after sowing). The forage collected was composed of all biomass available  in 2 mer (NDF) .2). A total of 15 animals (Girolando dairy cows) were used in a rotational grazing scheme according to target sward height management, 35 cm pre-grazing, and 25 cm post-grazing  present in the field was maintained and used for livestock grazing during the following year. The area was divided into eight paddocks  and grazed by 15 animals (Girolando dairy cows) in a rotational grazing scheme following the same management , 0.75 Ca (cmolc dm–3), 0.3 Mg (cmolc dm–3), 1.05 Ca + Mg (cmolc dm–3), 0.1 Al (cmolc dm–3), 2.55 H + Al (cmolc dm–3), 3.8 CEC (cmolc dm–3), 1 P Melich (mg dm–3), 70 K (mg dm–3), 14 Organic Matter (g.kg–1), 11.5 Aluminium saturation (%), and 31% of Base saturation (V%).The soil samples for chemical analyses were composed of five subsamples collected in each area  at 0–20 cm depth that were homogenized prior to measurement. These samples were used for the characterization of the soil before the beginning of the recovering process (collected in June 2017) and after the first year of recovery management (July 2018). The average soil textures for clay, silt, and sand were 24, 12, and 64% (0–20 cm), respectively. The average chemical composition was 4.6 pH . Each sample consisted of three subsamples obtained within a radius of 3 m, which were duly homogenized. The collection points of the samples between treatments were less than 160 m apart. The samples for microbial diversity analyses were at 5–10 cm depth.The sampled soil was sieved (2-mm-mesh sieve) and placed in 50-mL tubes, which were properly sealed, identified, and immediately placed in liquid nitrogen. In the laboratory, the samples were stored in a freezer at −80°C until processing.TM 1000 spectrophotometry  and sequenced on an Illumina MiSeq PE3000 platform  and CD Genomics .Total DNA was extracted from each of the 12 soil samples using the DNeasy PowerSoil Kit  following the manufacturer’s instructions. For bacteria, the V3-V4 regions of the bacterial 16S rRNA gene were amplified using the universal primers 515F  and 806RThe sequence data demultiplexed were imported into the Quantitative Insights into Microbial Ecology 2 , and Pielou evenness indices were estimated for each of the samples from the ASV table using the software R v.4.0.2  through PRJNA669331.The crude reads were deposited at the National Center for Biotechnology Information (NCBI) with BioProject accession number The results of the soil chemical analysis in the first year of recovering process are shown in –1 of corn, 1.7 Mg.ha–1 of pigeon pea, and 4.9 Mg.ha–1 grass, totaling 13.8 Mg.ha–1 of total forage, on a dry matter basis. Therefore, the silage dry matter was composed of 52.2% of corn, 12.3% of pigeon pea, and 35.5% of Tamani grass. The chemical composition of the silage was 0.3, 0.1, 7.8, 28.2, 3.5, 5.8, 64.1, 42.6, and 59.9% for Ca, P, CP, CF, EE, MM, TDN, ADF, and NDF, respectively. These results demonstrate the capacity of CLIS to produce high-quality forage in a great amount.Crop-livestock integrated system represented the crop-livestock integrated system using a triple intercropping of corn, pigeon pea, and grass. The forage yield was 7.2 Mg.haAbout 2.3 million reads were obtained from the sequencing of the 16S rRNA. After applying quality filters, merging reads, and chimera removal, the 873,043 bacterial sequences were grouped into 12,299 ASVs distributed in 944 taxonomic groups at level 7 (species). From species-level classification, 733 species were found in the CLIS sample, representing the most diverse sample, followed by the LI sample (563 species), and NS (494 species). Among the species observed, 33.5% (316) corresponded to the bacterial core present in all sampled areas, regardless of the treatment. In another hand, 229, 82, and 103 OTUs were exclusive for CLIS, LI, and NS areas, respectively. Unclassified sequences, which corresponded to 0.012% of the total, were excluded from the analyses.p = 0.001).In order to verify the difference in the abundance of taxonomic groups among the different land managements, a non-metric multidimensional scaling analysis (NMDS) was applied. Phylum, Class, Order, and Family were able to group the samples according to land management, verified by PERMANOVA . These classes were also positively correlated with the first component in NMDS. Thermoleophilia, Actinobacteria, and Bacilli were more predominant in CLIS and LI and negatively correlated with the first component in NMDS. Ktedonobacteria were found significantly more abundant in LI (p = 0.05) and positively correlated with the second dimension in NMDS , Actinobacteria (10.6%), Acidobacteriaceae (8.7%), Verrucomicrobiae (8.1%), Thermoleophila (7.9%), and Ktedonobacteria (6.6%). The classes Verrucomicrobiae (13.4%), Acidobacteria (12.5%), Planctomycetes (8.1%), and Gammaproteobacteria (5%), were significantly more abundant in the NS area than in the CLIS  and LI treatments   and Acidobacteriales (6%) were significantly more abundant than in the CLIS  and LI  treatments. Solirubrobacterales were less abundant in the NS area. NMDS based on bacterial orders showed a higher separation of CLIS and LI in the second dimension, with only one observation of LI at the positive side. Ktedonobacterales abundance was higher in LI samples and negatively correlated with NMDS2, explaining the separation of LI to CLIS . RhizobiNon-metric multidimensional scaling analysis of soil bacterial community showed that dissimilarities at the family level were driven by sampling area , very siThe NS treatment shared 21 families with CLIS and six families with LI. The CLIS and LI areas shared 32 families. Twenty families were exclusive to the NS, 18 families were exclusive to LI, and 63 families were exclusive to the CLIS . XanthobAbout 2.6 million reads were obtained from the sequencing of the ITS region. After applying quality filters, merging reads, and chimera removal, the 1,716,917 fungal sequences were grouped into 12,610 ASVs distributed in 1094 taxonomic groups at level 7 (species). From species-level classification, 671 species were found in the NS, representing the most diverse sample, followed by the LI sample (505 species), and CLIS (499 species). Among the species observed, 15.3% (167) corresponded to the bacterial core present in all sampled areas, regardless of the treatment. In another hand, 149, 151, and 380 species were exclusive for CLIS, LI, and NS areas, respectively. Of the reads approved in the quality index, 26.4% were not classifiable from the database used and were not included in other analyses.p = 0.05), both phyla were positively correlated with the first dimension, related to separation between NS and the others . CLIS and LI showed less than 20% of the abundance of the Agaricomycetes. Eurotiomycetes, Sordariomycetes, and Dothideomycetes were less abundant in NS .Non-metric multidimensional scaling analysis for fungal orders showed a clear separation among areas . The NS The NMDS with fungal family data separated the three areas, the first dimension separated NS from others and the second dimension separated LI from CLIS . In NS, The abundances of the microbial communities obtained in each sample are shown in The bacterial diversity (Shannon-Wiener and Simpson indices) and Pielou evenness indices showed no differences among the sampled areas. However, the bacterial richness was higher in the CLIS than in the LI and NS. In the NS area, the fungal diversity and Pielou evenness indices were smaller than in CLIS and LI, while the fungal richness was higher in native savanna in comparison to CLIS and LI treatments .Since the experiment was conducted on a commercial farm, there were limitations to develop an experimental design with traditional repetitions. Therefore, we provided here a pilot case study to explore the potential impact of CLIS management on soil biodiversity and microbial structure, and the results obtained here were representative for the studied place, which is inserted in the Cerrado biome.The productivity achieved in three months, which was verified through phytotechnology and bromatological analyses of the forage, was included in this work to prove that the forage produced at CLIS is of higher quality compared to traditional production systems. Thus, it reinforces our hypothesis that CLIS promotes soil regeneration, besides being able to represent economic gains to the producer . The resThe culture-independent analysis revealed that the predominant phyla of bacteria were Proteobacteria, Actinobacteria, and Acidobacteria, which varied in abundance between the sampled areas. The differences in relative abundances suggest the influence of the different conditions of each area, such as soil pH, nutrients, and vegetation. Moisture, temperature, soil composition, and pH shape the bacterial community in the soil, and pH is one of the main influencers of bacterial diversity and richness . ZhalninProteobacteria, Actinobacteria, and Acidobacteria are often abundant phyla in Cerrado soil . Among tThe phylum Acidobacteria was found in greater abundance in the NS, which can be explained by the more acidic pH found in this area since the representatives of this group have tolerance to lower pH , which hThe phylum Chloroflexi was less abundant in NS and CLIS than LI. Representants of this phylum are markedly found in anaerobic habitats where play a role in fermentation and degradation of organic compounds to support their growth and that of other bacterial populations . It was The family Chthoniobacteraceae (phylum Verrucomicrobia) was most abundant in NS, while CLIS and LI showed abundances three times lower of this family. The variations in the abundances of the families found in the studied areas reinforce the idea of a seed microbial bank, which refers to the ability of an organism to decrease its metabolic activity in the face of adverse conditions while still living in that environment and later being reactivated under favorable conditions . This woThe CLIS had the highest bacterial richness among the studied areas. This result can be explained by the fact that the area contains cultivated plants in addition to animals. Different plants and root exudates attract different groups of microorganisms to the rhizosphere .According to the NMDS analyses, the three areas analyzed were grouped in different clusters. There was a more pronounced separation of the NS from the two recovered areas (CLIS and LI) when analyzing bacterial data. The fungal data showed a more pronounced separation of LI from the other two.The difference between the CLIS and LI areas shows that the compositions of the fungal and bacterial communities differed. Regarding the analysis of fungal sequences, the NS showed a dominance of the phylum Basidiomycota. The phylum Ascomycota predominated in CLIS and LI, which suggests that degradation in the areas could lead to the loss of basidiomycetes, and this niche is occupied by ascomycete fungi. The prevalence of ascomycetes has been correlated with human activity and the high tolerance to environmental stresses by representatives of the phylum . The chastricto sensu areas have shown that the predominant fungal phyla in dry seasons are Ascomycota and Basidiomycota (Studies on microbial diversity in Cerrado iomycota , which iiomycota . The conThe dominant family in NS was Hygrophoraceae, whose representatives are primarily found in undisturbed grassland habitats and are much rarer or absent in grasslands subject to agricultural intensification, which can characterize them as ecological indicators . Thus, iThis study evaluated the taxonomic composition of the bacterial and fungal communities of the soil in CLIS compared to LI and NS areas. The land-use type affected the taxonomic diversity of the soil microbiota. The analyses of the microbial community showed that after one year of intervention in the degraded area, the CLIS area already showed a more accelerated recovery than the LI area, mainly marked by the bacterial communities. The results presented here contribute to a better understanding of the factors that help to model the microbial communities in strategic systems used for the recovery of degraded areas and encourage the use of CLIS for those areas.PRJNA669331.The datasets generated for this study can be found in NCBI under BioProject accession number PS, TP, GJ, FC, EA, and DS contributed to the conception and design of the study. GJ, FC, and EA conducted the field work and the soil sampling. PS performed the DNA extraction and soil and DNA analysis. LO and AF conducted the bioinformatics. LO ran the statistical analysis. PS, LO, and EA wrote the manuscript. TP, EA, DS, WA, and FS contributed to the manuscript revision. FS contributed to the funding acquisition and supervision. All authors read and approved the submitted manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.