Impact of Regular Blood Donation on Body Iron Stores at Saudi Blood Donors

Introduction: One of the most frequent observations in long-term blood donation is chronic iron deficiency, which can develop into anaemia. The majority of blood screening methods employed by blood banks do not incorporate iron-status markers, which may result in potential subclinical iron deficiency. The aim of this study was to evaluate the effects of repeated blood donation on the levels of iron in the body and to guide blood donors in preventing the depletion of iron stores. Methods: Regular blood donors were categorised into distinct groups according to the number of donations they gave, and then the correlation between these groups and their bodies’ iron levels was examined. Different parameters were employed to identify iron deficiency and iron depletion in blood donors: serum ferritin, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), total iron-binding capacity (TIBC), and serum iron. Results: The study included 300 individuals who regularly and willingly donated blood. There were no iron insufficiency cases among those donating blood for the first time (Group I). However, 15.5% of individuals who had donated once before (Group II) had ferritin levels of 15 - 30 μg/dl (ng/ml), indicating reduced iron stores. The rate increased to 18% (37 out of 206 individuals) among regular blood donors (Groups III, IV, and V). Iron deficiency (depletion) prevalence among regular blood donors in Groups III, IV, and V was 5.9% (12 out of 206) and 50.4% (100 out of 206). Donors who had donated blood most frequently had the lowest levels of haematological markers MCH, MCHC, and TIBC. Provide the p-values representing the differences between the means of MCV, MCH, iron, TIBC, and ferritin levels when comparing donor groups with the control group (Group I) based on the frequency of donations. Indicate statistically significant differences where the p-value is less than 0.0125. This significance level is adjusted based on the Bonferroni method, considering multiple independent tests. The result shows that the Iron parameter for the comparison between Group I and Group III and Group I and Group IV suggests a statistically significant difference in iron levels between these donor groups. Conclusion: The findings of this study show that a higher times of donations lads to a higher occurrence of depleted iron stores and subsequent erythropoiesis with iron deficiency by one donor from every three healthy donors. The iron and ferritin concentrations were within the normal range in group one (Control group) and reduced in the other four groups (G-2 to G-5). However, the level of haemoglobin remained within an acceptable range for blood donation. This outcome suggests that it may be necessary to reassess the criteria for accepting blood donors. The average serum ferritin levels were examined in all five groups (G-1 to G-5), both for males and females, and significant variations were seen among the groups under study. This study found that 35% of the individuals who regularly donate blood have iron-deficient anaemia (sideropenia). This suggests that it would be beneficial to test for serum ferritin at an earlier stage, ideally after three donations.

Alternative splicing of the PECTINESTERASE gene encoding a cell wall-degrading enzyme affects postharvest softening in grape

The firmness of table grape berries is a crucial quality parameter. Despite extensive research on postharvest fruit softening, its precise molecular mechanisms remain elusive. To enhance our comprehension of the underlying molecular factors, we initially identified differentially expressed genes(DEGs) by comparing the transcriptomes of folic acid(FA)-treated and water-treated(CK) berries at different time points. We then analyzed the sequences to detect alternatively spliced(AS) genes associated with postharvest softening. A total of 2,559 DEGs were identified and categorized into four subclusters based on their expression patterns, with subcluster-4 genes exhibiting higher expression in the CK group compared with the FA treatment group. There were 1,045 AS-associated genes specific to FA-treated berries and 1,042 in the CK-treated berries, respectively. Gene Ontology(GO) annotation indicated that the AS-associated genes in CK-treated berries were predominantly enriched in cell wall metabolic processes,particularly cell wall degradation processes. Through a comparison between treatment-associated AS genes and subcluster-4 DEGs, we identified eight genes, including Pectinesterase 2(VvPE2, Vitvi15g00704), which encodes a cell wall-degrading enzyme and was predicted to undergo an A3SS event. The reverse transcription polymerase chain reaction further confirmed the presence of a truncated transcript variant of VvPE2 in the FA-treated berries.Our study provides a comprehensive analysis of AS events in postharvest grape berries using transcriptome sequencing and underscores the pivotal role of VvPE2 during the postharvest storage of grape berries.

Reasons and effects of the decline of willing related potential living kidney donors

BACKGROUND Although the availability of related living donors(LDs)provides a better chance for receiving kidney transplantation(KT),the evaluation protocols for LD selection remain a safeguard for the LD’s safety.These protocols are variable from one center to another,resulting in variable rates of decline of the potential LDs(PLDs).The decline of willing PLDs may occur at any stage of evaluation,starting from the initial contact and counseling to the day of operation.AIM To identify the causes of the decline of PLDs,the predictors of PLD candidacy,and the effect on achieving LDKT.METHODS A retrospective study was performed on the willing PLDs who attended our outpatient clinic for kidney donation to their related potential recipients between October 2015 and December 2022.The variables influencing their candidacy rate and the fate of their potential recipients were studied.Two groups of PLDs were compared:Candidate PLDs after a completed evaluation vs non-candidate PLDs with a complete or incomplete evaluation.A multivariate logistic regression was performed to assess the factors contributing to the achievement of PLD candidacy.RESULTS Of 321 willing PLDs,257 PLDs(80.1%)accessed the evaluation to variable extents for 212 potential recipients,with a mean age(range)of 40.5±10.4(18-65)years,including 169 females(65.8%).The remaining 64 PLDs(19.9%)did not access the evaluation.Only 58 PLDs(18.1%)succeeded in donating,but 199 PDLs(62.0%)were declined;exclusion occurred in 144 PLDs(56.0%)for immunological causes(37.5%),medical causes(54.9%),combined causes(9.7%),and financial causes(2.1%).Regression and release occurred in 55 PLDs(17.1%).The potential recipients with candidate PLDs were not significantly different from those with non-candidate PLDs,except in age(P=0.041),rates of completed evaluation,and exclusion of PLDs(P<0.001).There were no factors that independently influenced the rate of PLD candidacy.Most patients who failed to have KT after the decline of their PLDs remained on hemodialysis for 6 mo to 6 years.CONCLUSION The rate of decline of willing related PLDs was high due to medical or immunological contraindications,release,or regression of PLDs.It reduced the chances of high percentages of potential recipients in LDKT.

Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

Robotic surgery and liver transplantation:A single-center experience of 501 robotic donor hepatectomies

Background:Over the past two decades robotic surgery has been introduced to many areas including liver surgery.Laparoscopic liver surgery is an alternative minimally invasive approach.However,moving on to the complexity of living donor hepatectomies,the advantages of robotic versus laparoscopic approach have convinced us to establish the robotic platform as a standard for living donor hepatectomy.Methods:From November 2018 to January 2022,501 fully robotic donor hepatectomies,including 177 left lateral donor lobes,112 full left lobes and 212 full right lobes were performed.Grafts were donated to 296 adult recipients and 205 pediatric recipients.Donor age,sex,body weight,body mass index(BMI),graft weight,graft to body weight ratio(GBWR),operative time,blood loss,first warm ischemic time,pain score,length of intensive care unit(ICU)stay and hospital stay,and complications were retrospectively analyzed based on a prospectively kept database.Recipients were evaluated for graft and patient survival,age,sex,BMI,body weight,model of end-stage liver disease score,blood loss,transfusions,operative time,cold ischemic time,length of hospital stay and complications.Results:There was no donor mortality.Two cases needed to be converted to open surgery.The median blood loss was 60 mL(range 20-800),median donor operative time was 6.77 h(range 2.93-11.53),median length of hospital stay was 4 days(range 2-22).Complication rate in donors classified following ClavienDindo was 6.4%(n=32)with one grade Ⅲ complication.Three-year actual recipient overall survival was 91.4%;87.5% for adult recipients and 97.1% for pediatric recipients.Three-year actual graft overall survival was 90.6%;87.5% for adult recipients and 95.1% for pediatric recipients.In-hospital mortality was 6%,9.1%(27/296)for adult recipients and 1.4%(3/205)for pediatric recipients.The recipients’morbidity was 19.8%(n=99).Twenty-eight recipients(5.6%)had biliary and 22(4.4%)vascular complications.Six(12.0%)recipients needed to be re-transplanted.Conclusions:With growing experience it is nowadays possible to perform any donor hepatectomy by robotic approach regardless of anatomical variations and graft size.Donor morbidity and quality for life results are encouraging and should motivate other transplant centers with interest in minimally invasive donor surgery to adopt this robotic technique.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.

Borderline resectable giant hepatic cavernous hemangioma and coexisting hemangiomatosis should be a new indication for living donor liver transplantation:A report of two cases

To the Editor:Hemangioma is a benign liver tumor that rarely requires treatment if the patient is asymptomatic[1].However,great cavernous hemangioma(GCH)can lead to symptoms due to its mass effect and Kasabach-Merritt syndrome(KMS)[2].GCH treatment options vary;therefore,tailoring treatment to individual patients according to their condition,such as symptoms,tumor location,and liver function,is important.Occasionally,GCH is associated with hemangiomatosis,and its boundaries with normal tissue are unclear[3],leading to a lack of consensus on the initial therapeutic approach,with literature primarily comprising case reports or series[4].This study presented two cases of GCH and coexisting hemangiomatosis;the patients underwent liver resection of the main mass to relieve symptoms but ultimately required liver transplantation(LT).We aimed to describe the role of LT in these patients.

The prediction of donor number and acceptor number of electrolyte solvent molecules based on machine learning

Electrolyte solvents have a critical impact on the design of high performance and safe batteries.Gutmann's donor number(DN) and acceptor number(AN) values are two important parameters to screen and design superior electrolyte solvents. However, it is more time-consuming and expensive to obtain DN and AN values through experimental measurements. Therefore, it is essential to develop a method to predict DN and AN values. This paper presented the prediction models for DN and AN based on molecular structure descriptors of solvents, using four machine learning algorithms such as Cat Boost(Categorical Boosting), GBRT(Gradient Boosting Regression Tree), RF(Random Forest) and RR(Ridge Regression).The results showed that the DN and AN prediction models based on Cat Boost algorithm possesses satisfactory prediction ability, with R^(2) values of the testing set are 0.860 and 0.96. Moreover, the study analyzed the molecular structure parameters that impact DN and AN. The results indicated that TDB02m(3D Topological distance based descriptors-lag 2 weighted by mass) had a significant effect on DN, while HATS1s(leverage-weighted autocorrelation of lag 1/weighted by I-state) plays an important role in AN. The work provided an efficient approach for accurately predicting DN and AN values, which is useful for screening and designing electrolyte solvents.

Molecular Characterization of RHD in Rh-Negative Blood Donors in Congo Brazzaville

Background: The D antigen is the most important and immunogenic antigen of the Rh blood group;its correct screening prevents any risk of alloimmunization in the RHD negative recipient. The D negative phenotype is characterized by the absence of the D antigen (RH1) on the surface of the erythrocyte. Three main mechanisms can generate this absence: total or partial deletion of the RHD gene, insertion of base pairs within the said gene and gene conversion. The objective of this study was to report the first data on RHD genotyping in RHD negative congolese blood donors. Materials and Methods: Blood samples came from regular RHD-negative blood donors selected from the blood transfusion stations in Brazzaville and Pointe-Noire. They were analyzed individually by conventional PCR, targeting exons 4, 5, 7 and 10 of the RHD gene. Results: Fifty-nine regular RHD negative blood donors were selected for this study. The immuno-hematological profile was determined individually, and the dccee phenotype was the most frequent (n = 52;88.1%). The search for the weak D antigen was negative for all donors. Exons 4, 5, 7 and 10 of the RHD gene were amplified in the following respective proportions: 89.8%, 81.4%, 6.8% and 42.4%. Moreover, (1) donor was found to carry all four specific exons sought. Conclusion: Conventional PCR amplification allowed to study the presence of specific exons of the targeted D gene. At least one exon was detected in the entire study population. These results suggest that the RHD gene is indeed present in the donors studied and that the deletion cannot be considered as the main mechanism causing the RH-1 (D negative) phenotype in this sample.

Phase engineering of a donor-doped air electrode for reversible protonic ceramic electrochemical cells

Reversible protonic ceramic electrochemical cells(R-PCECs)demonstrate great feasibility for efficient energy storage and conversion.One critical challenge for the development of R-PCECs is the design of novel air electrodes with the characteristics of high catalytic activity and acceptable durability.Here,we report a donor doping of Hf into the B-site of a cobalt-based double perovskite with a nominal formula of PrBa_(0.8)Ca_(0.2)Co_(1.9)Hf_(0.1)O_(5tδ)(PBCCHf_(0.1)),which is naturally reconfigured to a double perovskite PrBa_(0.8-x)Ca_(0.2)Co_(1.9)Hf_(0.1)-xO5tδ(PBCCHf_(0.1)-x)backbone and nano-sized BaHfO3(BHO)on the surface of PBCCHf_(0.1)x.The air electrode demonstrates enhanced catalytic activity and durability(a stable polarization resistance of 0.269Ωcm2 for~100 h at 600℃),due likely to the fast surface exchange process and bulk diffusion process.When employed as an air electrode of R-PCECs,a cell with PBCCHf_(0.1) air electrode demonstrates encouraging performances in modes of the fuel cell(FC)and electrolysis(EL)at 600℃:a peak power density of 0.998 W cm^(-2)and a current density of1.613 A cm^(-2)at 1.3 V(with acceptable Faradaic efficiencies).More importantly,the single-cell with PBCCHf_(0.1) air electrode demonstrates good cycling stability,switching back and forth from FC mode to EL mode0.5 A cm^(-2)for 200 h and 50 cycles.

High donor-number and low content electrolyte additive for stabilizing zinc metal anode

The aqueous zinc ion batteries(AZIBs)are thought as promising competitors for electrochemical energy storage,though their wide application is curbed by the uncontrollable dendrite growth and gas evolution side reactions.Herein,to stabilize both zinc anodes and water molecules,we developed a modified electrolyte by adding a trace amount of N,N-diethylformanmide(DEF)into the ZnSO_(4)electrolyte for the first time in zinc ion batteries.The effectiveness of DEF is predicted by the comparison of donor number and its preferential adsorption behavior on the zinc anode is further demonstrated by several spectroscopy characterizations,electrochemical methods,and molecular dynamics simulation.The modified electrolyte with 5%v.t.DEF content can ensure a stable cycling life longer than 3400 h of Zn‖Zn symmetric cells and an ultra-reversible Zn stripping/plating process with a high coulombic efficiency of 99.7%.The Zn‖VO_(2)full cell maintains a capacity retention of 83.5%and a 104 mA h g^(-1)mass capacity after 1000cycles.This work provides insights into the role of interfacial adsorption behavior and the donor number of additive molecules in designing low-content and effective aqueous electrolytes.

Perceptions of Mothers with Preterm Babies towards Donor Breast Milk at Women and Newborn Hospital,Lusaka Zambia

Breast milk offers essential nutrients crucial for the development of the preterm immune system, thus reducing the incidence of infection and mortality often associated with prematurity. In the absence of breast milk, the preferred option is donated breast milk, the best alternative for hospitalized neonates whose mothers have insufficient breast milk or are unavailable. In Zambia, donor breast milk is unavailable. Instead, the protocol recommends the administration of formula milk. However, the use of formula milk in preterm babies is associated with an increased risk of necrotizing enterocolitis and sepsis. Zambia needs to establish a donor milk bank, hence the need to understand the perception of mothers towards donated breast milk. A qualitative descriptive case study utilized 10 focus group discussions with in-depth interviews, purposively selected using a variation strategy. Data was thematically analysed. Participants demonstrated potential acceptance to donor breast milk utilization, as more nutritional compared to formula despite lack of awareness. Concerns related to safety, quality, fear of disease transmission and discomfort feeding from a different bloodline were identified as hinderance to possible utilisation. These perceptions underscore the importance of educational initiatives aimed at dispelling myths and misconceptions surrounding donor breast milk and establishing donor breast milk programs. Therefore, the study recommends educational initiatives tailored to raise awareness to mothers about donor breast milk.

Quality of Life in Living Kidney Donors Grenoble Teaching Hospital (France)

Context: Kidney transplantation is today the standard treatment for patients suffering from chronic end-stage renal failure. Living kidney donation offers many advantages for the recipient, but requires a subject without comorbidities to undergo surgery. The aim of this study was to assess the quality of life and psychosocial experience of living kidney donors after donation. Methods: This was a cross-sectional study with an analytical aim, involving living kidney donors during the period from January 2016 to April 2019 at CHUGA. (University Hospital Center of Grenoble Alpes in France). Results: Our study shows that out of 88 donors, 70 responded to our questionnaires, representing a prevalence of 80.5%. The average age of our donors was 55.6 years with a female predominance. Seven out of eight domains of the SF36 score had a good quality of life after donation and the donation did not alter their psychosocial experience. The majority of our donors expressed their pride and enthusiasm, did not regret having saved a life, and this experience was considered positive. Conclusion: Kidney donation does not have a negative impact on quality of life and psychosocial life. The majority of donors do not regret their donation. The dissemination of such results could make it possible to increase the number of kidney transplants from living donors in France, especially in our African countries where the management of ESRD remains a real public health problem.

A Neural-network-based Alternative Scheme to Include Nonhydrostatic Processes in an Atmospheric Dynamical Core

Here,a nonhydrostatic alternative scheme(NAS)is proposed for the grey zone where the nonhydrostatic impact on the atmosphere is evident but not large enough to justify the necessity to include an implicit nonhydrostatic solver in an atmospheric dynamical core.The NAS is designed to replace this solver,which can be incorporated into any hydrostatic models so that existing well-developed hydrostatic models can effectively serve for a longer time.Recent advances in machine learning(ML)provide a potential tool for capturing the main complicated nonlinear-nonhydrostatic relationship.In this study,an ML approach called a neural network(NN)was adopted to select leading input features and develop the NAS.The NNs were trained and evaluated with 12-day simulation results of dry baroclinic-wave tests by the Weather Research and Forecasting(WRF)model.The forward time difference of the nonhydrostatic tendency was used as the target variable,and the five selected features were the nonhydrostatic tendency at the last time step,and four hydrostatic variables at the current step including geopotential height,pressure in two different forms,and potential temperature,respectively.Finally,a practical NAS was developed with these features and trained layer by layer at a 20-km horizontal resolution,which can accurately reproduce the temporal variation and vertical distribution of the nonhydrostatic tendency.Corrected by the NN-based NAS,the improved hydrostatic solver at different horizontal resolutions can run stably for at least one month and effectively reduce most of the nonhydrostatic errors in terms of system bias,anomaly root-mean-square error,and the error of the wave spatial pattern,which proves the feasibility and superiority of this scheme.

Improved genome annotation of Brassica oleracea highlights the importance of alternative splicing

Brassica oleracea has been developed into many important crops,including cabbage,kale,cauliflower,broccoli and so on.The genome and gene annotation of cabbage(cultivar JZS),a representative morphotype of B.oleracea,has been widely used as a common reference in biological research.Although its genome assembly has been updated twice,the current gene annotation still lacks information on untranslated regions(UTRs)and alternative splicing(AS).Here,we constructed a high-quality gene annotation(JZSv3)using a full-length transcriptome acquired by nanopore sequencing,yielding a total of 59452 genes and 75684 transcripts.Additionally,we re-analyzed the previously reported transcriptome data related to the development of different tissues and cold response using JZSv3 as a reference,and found that 3843 out of 11908 differentially expressed genes(DEGs)underwent AS during the development of different tissues and 309 out of 903 cold-related genes underwent AS in response to cold stress.Meanwhile,we also identified many AS genes,including BolLHCB5 and BolHSP70,that displayed distinct expression patterns within variant transcripts of the same gene,highlighting the importance of JZSv3 as a pivotal reference for AS analysis.Overall,JZSv3 provides a valuable resource for exploring gene function,especially for obtaining a deeper understanding of AS regulation mechanisms.

Seroprevalence of Human Immunodeficiency Virus and Hepatitis B in Blood Donors at the N’Zérékoré Regional Blood Transfusion Centre in Guinea

Blood transfusion saves lives and reduces morbidity and mortality for a large number of diseases and clinical conditions, but it is not without danger. The aim of this study was to determine the seroprevalence of HIV and hepatitis B in blood donors received at the regional Blood Transfusion Centre of N’Zérékoré (Guinea). This was a 5-year retrospective analytical study. We included records of blood donors aged 18 to 60 years admitted to the N’Zérékoré Regional Blood Transfusion Centre for blood donation from January 2016 to December 2020. We performed a descriptive analysis followed by Chi-2 or Fish-er-exact tests and the Student or Wilcoxon test, followed by multivariate logistic regression. In this study, donor age ranged from 18 - 60 years, with a pre-dominance of donors aged 25 - 34 (44.2%). Male donors were the most represented in our study (79.0% versus 21.0% female). More than half of the donors were blood group O (55.6%). We observed a seroprevalence of 3.6% for HIV, 13.4% for HBsAg and 0.2% for co-infection. In our series, age 25 - 34 (OR = 1.89 and P = 0.001) and 35 - 44 for HIV (OR = 2.01 and P = 0.001), HBsAgserostatus (OR = 3.04 and P = 0.001) and blood donation history (OR of 3.04 and P = 0.001) were factors associated with HIV positivity (P < 0.05). In our study, HIV serostatus (OR = 3.04 and P = 0.001) and blood donation history (OR = 0.01 and P = 0.001) were factors associated with HBsAgseropositivity. We reported a high prevalence of HIV and HBsAg. Sex, serological status and blood donation history were associated factors.

2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-Glucoside modulates CHEK2 and CCND1 alternative splicing to inhibit MCF-7 cells proliferation

Background:In our previous study,we observed a synergistic effect of 2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-glucoside combined with adriamycin to induce apoptosis in MCF-7 breast cancer cells.However,the underlying mechanisms of epigenetic modifications,such as alternative splicing,have not been explored.In this study,we aimed to investigate the mechanism by which THSG inhibits MCF-7 cell proliferation using full-length transcriptome sequencing.Methods:First,cell viability was examined using the methyl thiazolyl tetrazolium method and full-length transcriptome sequencing was performed to identify genes and pathways.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to identify the principal pathways and targets of THSG.Flow cytometry analysis of cell cycle distribution was performed.Meanwhile,the analysis of alternative splicing and domains of the key proteins was conducted.Quantitative polymerase chain reaction and western blotting were performed for verification.Results:THSG showed significant cytotoxic activity in MCF-7 cells.Full-length transcriptome sequencing revealed differential alternative splicing with 173 upregulated and 263 downregulated genes.Further analysis identified distinct differential expression of genes(CHEK2-211 and CCND1-201)involved in the cell cycle in the THSG-treated group.Subsequently,alternative splicing types of CHEK2(mutually exclusive exon)and CCND1(intron retention).We found that THSG downregulated mRNA expression,as confirmed by quantitative polymerase chain reaction analysis.Interestingly,protein structural analysis revealed that THSG treatment led to the generation of CHK2-211,which was the result of a mutation in the amino acid residues(GLU-150,ASN-151)of the CHEK2 domain(VAL-150,GLY-151).and CyclinD1-201 were obtained when an amino acid(ASP-267)in the domain was lost in CyclinD1.Moreover,molecular docking analysis demonstrated that the domains of key proteins could bind THSG more effectively,with no difference in affinity.Western blotting confirmed that THSG inhibited the expression of CHK2 and CyclinD1.Conclusion:THSG modulated the alternative splicing of CHEK2 and CCND1 by inducing G0/G1 cell cycle arrest,consequently suppressing MCF-7 cell proliferation.

Workshop “Navigating the Transition: Standards Powering the Journey of Alternative Fuel Infrastructure”

April 18, Brussels, Belgium In light of recent significant regulatory changes within the European Union impacting the transport sector, such as the Alternative Fuels Infrastructure Regulation(AFIR), Re Fuel EU and Fuel EU Maritime, the role of European standardization becomes increasingly critical in facilitating the transition towards the deployment of alternative fuels.

Use of Topical Complementary and Alternative Medicines (CAM) in Diabetic Septic Foot Disease in Makkah Region, Western of Saudi Arabia, an Exploratory Study

Diabetes is a chronic condition that is significantly impacted daily by environment. At least one in five Saudis, suffer from diabetes. “Diabetes is a pandemic of unprecedented magnitude spiraling out of control” (Boulton). Saudi Arabia ranks the second highest in the Middle East, and is the seventh in the world for the prevalence of diabetes (WHO). Diabetes mellitus (DM) has been found to be related to high mortality, morbidity accompanied by poor general health and lower quality of life. Current Saudi diabetes patients’ behaviors, practices, and beliefs regarding foot health problems such as ulcers, are not well investigated. Diabetic patients frequently utilize natural remedies and Herbs for self-medication as a part of complementary and alternative Medicine. Aim of study: To explore the widespread use of the alternative remedies in the local communities of the Western Saudi Arabia, the drives behind using and to focus on the potential adverse effects following their usage. Method: A descriptive, cross-sectional study of 386 diabetic patients with feet problems in Makkah Region, West of Saudi Arabia during the period April - June 2023. Results: Out of the 531 participants, only 386 participants reported diabetic foot disorder (DFD). Most of the participant were above 65 years of age group (24.61 %). Male (52.08%) more than female (47.92%) in the research group. All of the participants had diabetic foot disorders at least once. The prevalence of complementary and alternative medicines (CAM) use among them was 67.88%, as solitary or in combination with hospital medicines. Honey headed the list followed by myrrh and black seeds. Acquaintances advice (59.54%) was the most reason for using the alternative medicine. 60.30% of Diabetic foot patient complained of adverse effects during CAM remedies use. Conclusion: Consumption of CAM remedies among diabetic patients for Diabetic Foot Disorder (DFD) is common. Honey headed the list followed by myrrh and black seeds. Additional wide-scale research is required to establish their actual efficacy, safety and potential adverse out-comes and to generalize the outcomes.

Influence of donor age on liver transplantation outcomes: A multivariate analysis and comparative study

BACKGROUND The growing disparity between the rising demand for liver transplantation(LT)and the limited availability of donor organs has prompted a greater reliance on older liver grafts.Traditionally,utilizing livers from elderly donors has been associated with outcomes inferior to those achieved with grafts from younger donors.By accounting for additional risk factors,we hypothesize that the utili-zation of older liver grafts has a relatively minor impact on both patient survival and graft viability.AIM To evaluate the impact of donor age on LT outcomes using multivariate analysis and comparing young and elderly donor groups.METHODS In the period from April 2013 to December 2018,656 adult liver transplants were performed at the University Hospital Merkur.Several multivariate Cox propor-tional hazards models were developed to independently assess the significance of donor age.Donor age was treated as a continuous variable.The approach involved univariate and multivariate analysis,including variable selection and assessment of interactions and transformations.Additionally,to exemplify the similarity of using young and old donor liver grafts,the group of 87 recipients of elderly donor liver grafts(≥75 years)was compared to a group of 124 recipients of young liver grafts(≤45 years)from the dataset.Survival rates of the two groups were estimated using the Kaplan-Meier method and the log-rank test was used to test the differences between groups.RESULTS Using multivariate Cox analysis,we found no statistical significance in the role of donor age within the constructed models.Even when retained during the entire model development,the donor age's impact on survival remained insignificant and transformations and interactions yielded no substantial effects on survival.Consistent insigni-ficance and low coefficient values suggest that donor age does not impact patient survival in our dataset.Notably,there was no statistical evidence that the five developed models did not adhere to the proportional hazards assumption.When comparing donor age groups,transplantation using elderly grafts showed similar early graft function,similar graft(P=0.92),and patient survival rates(P=0.86),and no significant difference in the incidence of postoperative complications.CONCLUSION Our center's experience indicates that donor age does not play a significant role in patient survival,with elderly livers performing comparably to younger grafts when accounting for other risk factors.