Changes In Levels Research Articles

Quantitative evaluation of endometrium-expressed mRNAs for the purpose of discriminating between menstruation and traumatic vaginal injury in sexual assault cases.

In sexual assault cases, it is crucial to discriminate between peripheral blood and menstrual blood to provide evidence for vaginal intercourse with traumatic injury. In this study, the menstrual blood mRNA markers progestagen-associated endometrial protein (PAEP), matrix metallopeptidase 7 (MMP7), and left-right determination factor 2 (LEFTY2) were evaluated by quantitative RT-PCR (RT-qPCR) for the discrimination of menstrual blood from peripheral blood and vaginal fluid. As a result, all markers with cutoff delta cycle quantification (ΔCq) values were specifically determined in menstrual blood among forensically relevant body fluids. Even though the changes in the expression levels of each marker differed during the menstrual cycle, all markers were determined to be positive in most of the randomly collected menstrual blood samples that were analyzed. Additionally, the markers with proposed cutoff ΔCq values could discriminate between menstrual blood and peripheral blood-mixed vaginal fluid samples. The determination of positive markers was less affected by storage temperature under dry conditions than under wet conditions, while PAEP was detectable in samples stored below room temperature under wet conditions. The detectability of PAEP was considered to be the result of its higher expression level compared with MMP7 and LEFTY2. In conclusion, menstrual blood markers for the RT-qPCR procedure evaluated in this study were highly specific for menstrual blood. The proposed procedure could be useful for discriminating between menstruation and traumatic bleeding in the female genital tract. In particular, PAEP is expected to be applicable to forensic casework samples because of its high specificity and robustness.

A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT.

The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro. Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets). Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts. Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.

Characteristics and influencing factors of farmland abandonment in the karst rocky desertification area of Southwest China

Owing to rocky desertification, farmland abandonment in karst areas is different from that in normal landforms. Aiming at the phenomenon of large-scale farmland abandonment in the karst region of Southwest China, this study investigated the characteristics of farmland abandonment in different rocky desertification control areas of typical counties. We interpreted land use changes in the study area using high-resolution images (5 m) in 2010 and 2020 through human–computer interaction. After removing patches of converted farmland to forests, we extracted the spatial distribution of abandoned farmland. The study area was found to have a high abandonment rate (24.83 %), with dryland showing 2–3 times higher abandonment rate than paddy fields. The abandoned area in rocky desertification dryland accounts for 50.57 % (499.04 km2) of the abandoned area of karst dryland. It is worth noting that the abandonment rate of non-rocky desertification dryland in the karst dryland is the lowest (22.45 %), while the abandonment rate of dryland shows no significant difference among other rocky desertification grades, with an average of 28.00 %. In addition, with the change of rocky desertification level, the index of abandonment degree showed a trend of initial increase followed by a decrease. Slope, lithology and soil type have a joint effect on karst dryland abandonment. Slope is the core factor affecting karst dryland abandonment, and the interaction between slope and soil type is the dominant factor affecting its change. The results of this study show that farmland abandonment is serious in karst rocky desertification areas, primarily occurring in rocky desertification dryland. The government should take targeted management measures based on the current status of abandoned drylands at different levels of rocky desertification, especially in sloping farmland areas.

Thermal adaptation involves higher expression levels of the lethal(2)-essential-for-life-like (l(2)efl) among the honeybee Apis mellifera L. subspecies

Apis mellifera yemenitica is the native honeybee of the Arabian Peninsula. It demonstrates unique morphological, behavioral, and molecular aspects to survive extreme summer temperatures dominating the region. In this study, relative expression of Apis mellifera lethal(2)-essential-for-life-like (l(2)efl) gene family (ID: 724405; 724488; 234274) were measured in A. m. yemenitica and A. m. carnica under desert (Riyadh) and semiarid (Baha) conditions of Saudi Arabia. Results demonstrated significantly higher day-long expression levels of l(2)efl mRNAs in A. m. yemenitica than in A. m. carnica under the same conditions. Under desert conditions of Riyadh, fold changes in expression levels of l(2)efl mRNAs were ∼100× higher in A. m. yemenitica than the calibrator. In Baha (semiarid conditions), l(2)efl expression levels were very modest compared to those in Riyadh with significant interaction between location and subspecies. In conclusion, expression of l(2)efl (mRNAs) (724405; 724488; 234274) can be considered as a key component of A. m. yemenitica response to extreme desert temperatures characterizing the Riyadh region. On the other hand, the semi-arid conditions (Baha) are a more suitable habitat for A. m. carnica compared to Riyadh.

Antidepressant Dispensing to US Adolescents and Young Adults: 2016-2022.

Mental health worsened in adolescents and young adults after the coronavirus disease 2019 (COVID-19) outbreak in March 2020, but whether antidepressant dispensing to this population changed is unknown. We identified antidepressant prescriptions dispensed to US individuals aged 12 to 25 years from 2016 to 2022 using the IQVIA Longitudinal Prescription Database, an all-payer national database. The outcome was the monthly antidepressant dispensing rate, defined as the monthly number of individuals with ≥1 dispensed antidepressant prescription per 100 000 people. We fitted linear segmented regression models assessing for level or slope changes during March 2020 and conducted subgroup analyses by sex and age group. Between January 2016 and December 2022, the monthly antidepressant dispensing rate increased 66.3%, from 2575.9 to 4284.8. Before March 2020, this rate increased by 17.0 per month (95% confidence interval: 15.2 to 18.8). The COVID-19 outbreak was not associated with a level change but was associated with a slope increase of 10.8 per month (95% confidence interval: 4.9 to 16.7). The monthly antidepressant dispensing rate increased 63.5% faster from March 2020 onwards compared with beforehand. In subgroup analyses, this rate increased 129.6% and 56.5% faster from March 2020 onwards compared with beforehand among females aged 12 to 17 years and 18 to 25 years, respectively. In contrast, the outbreak was associated with a level decrease among males aged 12 to 17 years and was not associated with a level or slope change among males aged 18 to 25 years. Antidepressant dispensing to adolescents and young adults was rising before the COVID-19 outbreak and rose 63.5% faster afterward. This change was driven by increased antidepressant dispensing to females and occurred despite decreased dispensing to male adolescents.

Estimating and Assessing Monthly Water Level Changes of Reservoirs and Lakes in Jiangsu Province Using Sentinel-3 Radar Altimetry Data

Generating accurate monthly estimations of water level fluctuations in reservoirs and lakes is crucial for supporting effective water resource management and protection. The dual-satellite configuration of Sentinel-3 makes it possible to monitor water level changes with great coverage and short time intervals. However, the potential of Sentinel-3’s Synthetic Aperture Radar Altimetry (SRAL) data to enable operational monitoring of water levels across Jiangsu Province on a monthly basis has not yet been fully explored. This study demonstrated and validated the use of Sentinel-3’s SRAL to generate accurate monthly water level estimations needed to inform water management strategies. The monthly water levels of lakes and reservoirs from 2017 to 2021 were produced using Sentinel-3 level-2 land products. Results showed that, compared with in situ data across eight studied lakes, all lakes presented R (Pearson correlation coefficient) values greater than 0.5 and Root Mean Square Error (RMSE) values less than 1 m. Notably, water level estimates for Tai Lake, Gaoyou Lake, and Luoma Lake were particularly accurate, with R above 0.9 and RMSE below 0.5 m. Furthermore, the monthly water level estimates derived from the Sentinel-3 data showed consistent seasonal trends over the multi-year study period. The annual water level of all lakes did not change significantly, except for Shijiu Lake, of which the difference between the highest and lowest water level was up to about 5 m. Our findings confirmed the water level observation ability of Sentinel-3. The accuracy of water level monitoring could be influenced by internal water level differences, terrain features, as well as the area and shape of the lake. Larger lakes with more altimetry sampling points tended to yield higher accuracy estimates of water level fluctuations. These results demonstrate that the frequent, wide-area coverage offered by this satellite platform provides valuable hydrological information, especially across remote regions lacking in situ data. Sentinel-3 has immense potential to support improved water security in data-scarce regions.

Changes in Level of Steroacuity in Patients Having Different Types of Refractive Errors

Purpose: To find out the frequency of stereoacuity in different refractive errors in patients visitingophthalmology department of The University of Lahore Teaching Hospital. Methodology: This was a descriptive cross-sectional study which recruited volunteers visiting department of ophthalmology at University of Lahore teaching hospital. After informed consent, he frequency of steroacuity level in all the participants were assessed using a proforma Steroacuity level was taken as normal (20 seconds of Arc), borderline (20-40 seconds of Arc) and reduced (above 40 seconds of Arc). The depth perception level among the patients of different types of refractive errors (Myopia, Hyperopia and Astigmatism), regardless of gender specific both male and female was examined with the age limit (15-35). SPSS 23 was employed for data analysis after the findings were recorded in proforma. Fried-man test was applied to find the statistical significance of data. P-value 0.05 was considered as significant. Results: A total of 145 people aged (15-35) years old, both genders (male, female) were included in the study. Fifty four (54) myopic participants out of 72, 34 astigmatic out of 55 and 12 hyperopic participants out of 18 had normal stereopsis. Ten (10) from 72 myopia participants, 11 from 55 astigmatism volunteers and 4 out of 18 hyperopic subjects had borderline steroacuity. Likewise, 8 out of 72 myopia patients, 10 out of 55 astigmatism patients and 2 out of 18 had a reduced Stereoacuity above 40 Arc. In overall comparison, 69.0 % were normal, 17.2% were borderline and 13.8% had reduced stereoacuity level with P value 0.0267. Conclusion: Our study shows that stereopsis was significantly reduced in those having astigmatism than those with myopia and hyperopia.

A preliminary study of dynamic neurochemical changes in the dorsolateral prefrontal cortex during working memory.

Working memory (WM) is one of the fundamental cognitive functions associated with the dorsolateral prefrontal cortex (DLPFC). However, the neurochemical mechanisms of WM, including the dynamic changes in neurometabolites such as glutamate and GABA in the DLPFC, remain unclear. Here, we investigated WM-related glutamate and GABA changes, alongside hemodynamic responses in the DLPFC, using a combination of functional magnetic resonance spectroscopy (fMRS) and functional magnetic resonance imaging (fMRI). During a WM task, we measured Glx (glutamate + glutamine) and GABA levels using GABA editing MEscher-GArwood Point REsolved Spectroscopy (MEGA-PRESS) sequence and blood-oxygen-level-dependent (BOLD) signal changes. In the DLPFC, we observed elevated Glx levels and increased BOLD signal changes during a 2-back task. Specifically, the Glx levels in the DLPFC were significantly higher during the 2-back task compared with fixation, although this difference was not significant when compared with a 0-back task. However, Glx levels during the 0-back task were higher than during fixation. Furthermore, there was a positive correlation between Glx levels in the DLPFC during the 2-back task and the corresponding BOLD signal changes. Notably, higher Glx increases were associated with increased DLPFC activation and lower WM task performance in individuals. No notable changes in DLPFC GABA levels were observed during WM processing. These findings suggest that the modulation of glutamatergic activity in the DLPFC may play a crucial role in both working memory processing and its associated performance outcomes.

Comprehensive evaluation of inactivated SARS-CoV-2 vaccination on sperm parameters and sex hormones.

The inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has made significant contributions to fighting the epidemic in the past three years. However, the rapid development and application raised concerns about its safety in reproductive health, especially after several studies had observed a decrease in semen parameters following two doses of mRNA SARS-CoV-2 vaccination. Thus, it is necessary to comprehensively evaluate the effect of inactivated SARS-CoV-2 vaccine on male fertility. A retrospective cohort study was conducted in the Center for Reproductive Medicine of the Affiliated Hospital of Jining Medical University between July 2021 and March 2023.A total of 409 men with different vaccination status and no history of SARS-CoV-2 infection were included in this study. Their sex hormone levels and semen parameters were evaluated and compared separately. The levels of FSH and PRL in one-dose vaccinated group were higher than other groups, while there were no significant changes in other sex hormone levels between the control and inactivated SARS-CoV-2 vaccinated groups. Most semen parameters such as volume, sperm concentration, total sperm count, progressive motility and normal forms were similar before and after vaccination with any single dose or combination of doses (all P > 0.05). Nevertheless, the total motility was significantly decreased after receiving the 1+2 doses of vaccine compared to before vaccination (46.90 ± 2.40% vs. 58.62 ± 2.51%; P = 0.001). Fortunately, this parameter was still within the normal range. Our study demonstrated that any single dose or different combined doses of inactivated SARS-CoV-2 vaccination was not detrimental to male fertility. This information could reassure men who want to conceive after vaccination and be incorporated into future fertility recommendations.

Evaluating the Performance-Based Grading of Construction Labour in Road Project Operations Through a New Apprenticeship Framework

The main issues facing the construction industry in many nations have been poor labour performance in work operations, leading to significantly influencing the quality, safety and productivity of construction processes/outcomes. By implementing efficient apprenticeship components, this study attempts to evaluate the effectiveness/performance of labour in road project operations through a case study. With action-oriented and problem-focused communication approaches, an exhaustive academic review and expert consultations were carried out to design a collection of methods/tools/systems linked to labour apprenticeship and performance assessment inside a framework. Through a newly established site supervisory apprenticeship programme, the developed procedures were implemented with more than 100 construction labourers engaged in nine Sri Lankan road projects. The results display the specific patterns of substantial changes in labour performance levels with the quantified values, which aid in the planning and formation of crew mixes for various project jobs, as well as proactive methods for managing and controlling labour in the construction industry. The findings ensure the generalisation of the developed practices/tools/mechanisms towards the sustainability of its applications. The study further adds advanced attributes to construction supervision job roles. The study findings/outcomes can make significant impacts on the practices of other developing nations and industries.

Development of Cilofexor, an intestinally-biased Farnesoid X Receptor agonist, for the treatment of fatty liver disease.

The farnesoid X receptor (FXR) is a nuclear receptor that controls bile acid, lipid, and cholesterol metabolism. FXR-targeted drugs have shown promise in late-stage clinical trials for non-alcoholic steatohepatitis. Herein, we used clinical results from our first non-steroidal FXR agonist, Px-102 (4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methoxy]phenyl]cyclopropyl] benzoic acid), to develop cilofexor, a potent, non-steroidal FXR agonist with a more manageable safety profile. Px-102 demonstrated the anticipated pharmacodynamic (PD) effects in healthy volunteers but caused a 2-fold increase in alanine aminotransferase (ALT) activity and changes in cholesterol levels. These data guided development of a high fat diet mouse model to screen FXR agonists based on ALT and cholesterol changes. Cilofexor was identified to elicit only minor changes in these parameters. The differing effects of cilofexor and Px-102 on ALT/cholesterol in the model could not be explained by potency or specificity, and we hypothesized that the relative contribution of intestinal and liver FXR activation may be responsible. Gene expression analysis from rodent studies revealed that cilofexor, but not Px-102, had a bias for FXR transcriptional activity in the intestine compared to the liver. Fluorescent imaging in hepatoma cells demonstrated similar subcellular localization for cilofexor and Px-102, but cilofexor was more rapidly washed out, consistent with a lower membrane residence time contributing to reduced hepatic transcriptional effects. Cilofexor demonstrated antisteatotic and antifibrotic efficacy in rodent models and antisteatotic efficacy in a monkey model, with the anticipated PD and a manageable safety profile in human phase I studies. Significance Statement FXR (farnesoid X receptor) agonists have shown promise in treating non-alcoholic steatohepatitis and other liver diseases in the clinic, but balancing efficacy with undesired side effects has been difficult. Here, we examined the preclinical and clinical effects of the first-generation FXR agonist, Px-102 (4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methoxy]phenyl]cyclopropyl] benzoic acid), to enable the selection of an analog, cilofexor, with unique properties that reduced side effects yet maintained efficacy. Cilofexor is one of few remaining FXR agonists in clinical development.

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT study).

Liver dysfunction contributes to worse clinical outcomes in heart failure (HF) patients. However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction. Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models. Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP. Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in heart failure with reduced ejection fraction patients in clinical practice.

Restoring functional TDP-43 oligomers in ALS and laminopathic cellular models through baicalein-induced reconfiguration of TDP-43 aggregates

A group of misfolded prone-to-aggregate domains in disease-causing proteins has recently been shown to adopt unique conformations that play a role in fundamental biological processes. These processes include the formation of membrane-less sub-organelles, alternative splicing, and gene activation and silencing. The cellular responses are regulated by the conformational switching of prone-to-aggregate domains, independently of changes in RNA or protein expression levels. Given this, targeting the misfolded states of disease-causing proteins to redirect them towards their physiological conformations is emerging as an effective therapeutic strategy for diseases caused by protein misfolding. In our study, we successfully identified baicalein as a potent structure-correcting agent. Our findings demonstrate that baicalein can reconfigure existing TDP-43 aggregates into an oligomeric state both in vitro and in disease cells. This transformation effectively restores the bioactivity of misfolded TDP-43 proteins in cellular models of ALS and premature aging in progeria. Impressively, in progeria cells where defective lamin A interferes with TDP-43-mediated exon skipping, the formation of pathological TDP-43 aggregates is promoted. Baicalein, however, restores the functionality of TDP-43 and mitigates nuclear shape defects in these laminopathic cells. This establishes a connection between lamin A and TDP-43 in the context of aging. Our findings suggest that targeting physiological TDP-43 oligomers could offer a promising therapeutic avenue for treating aging-associated disorders.

Ambulatory Percutaneous Nephrolithotomy: Initial Series in Iran

Background: Percutaneous nephrolithotomy (PCNL) procedures in the United States typically cost between 9000 to 16000 USD. In developing countries like Iran, healthcare performance is hindered by issues such as high bed occupancy rates. Therefore, performing PCNL in an outpatient setting could significantly reduce surgical costs and improve healthcare outcomes by reducing bed occupancy and associated complications. Objectives: This study aimed to explore the feasibility of same-day discharge for selected PCNL patients. Methods: Out of 142 patients, 32 were discharged within 12 hours post-operation (Study Group), while 32 randomly selected patients from the remaining 110 served as the control group. Same-day discharge criteria included stable vital signs, tolerance to oral intake, appropriate mobility, and normal laboratory results. Exclusion criteria encompassed the need for red blood cell transfusion, hemoglobin drops exceeding 2 mg/dL, and abnormal post-operative laboratory findings. Results: Patient characteristics and medical histories did not significantly differ between the study and control groups. Additionally, stone laterality (P-value = 0.606), location (P-value = 0.731), size (P-value = 0.334), and density (P-value = 0.065) showed no significant differences between the two groups. The post-surgical observation period in the study group (mean: 7.88 hours) was significantly shorter than that in the control group (mean: 62 hours) (P-value &lt; 0.001). The mean hemoglobin level change was 1.48 mg/dL (SD: ± 1.02) in the study group and 1.31 mg/dL (SD: ± 0.91) in the control group. Similarly, the change in creatinine levels was 0.13 ± 0.04 in the study group and 0.23 ± 0.03 in the control group. Conclusions: This study demonstrates that outpatient PCNL procedures are feasible without increasing perioperative complications. However, careful patient selection based on strict criteria is crucial for successful implementation.

A quasi-experimental evaluation of the association between implementation of Quality-Based Procedures funding for hip fractures and improvements in processes and outcomes for hip fracture patients in Ontario: an interrupted time series analysis.

In 2013, Ontario introduced a patient-based funding model for hip fracture care (Quality-Based Procedures [QBP]). The association of QBP implementation with changes in processes and outcomes has not been evaluated. We conducted a quasi-experimental study using linked health data for adult hip fractures as an interrupted time series. The pre-QBP period was from 2008 to 2012 and the post-QBP period was from 2014 to 2018; 2013 was excluded as a wash-in period. We used segmented regression analyses to estimate the association of QBP implementation with changes in processes (surgery in less than two days from admission, use of echocardiography, use of nerve blocks, and provision of geriatric care) and clinical outcomes (90-day mortality, 90-day readmissions, length of stay, and days alive at home). We estimated the immediate (level) change, trend (slope) postimplementation, and total counterfactual differences. Sensitivity analyses included case-mix adjustment and stratification by hospital type and procedure. We identified 45,500 patients in the pre-QBP period and 41,256 patients in the post-QBP period. There was a significant total counterfactual increase in the use of nerve blocks (11.1%; 95% confidence interval [CI], 6.2 to 16.0) and a decrease in the use of echocardiography (-2.5%; 95% CI, -3.7 to -1.3) after QBP implementation. The implementation of QBP was not associated with a clinically or statistically meaningful change in 90-day mortality, 90-day readmission, length of stay, or number of days alive at home. Evaluation of the QBP program is crucial to inform ongoing and future changes to policy and funding for hip fracture care. The introduction of the QBP Hip Fracture program, supported by evidence-based recommendations, was associated with improved application of some evidence-based processes of care but no changes in clinical outcomes. There is a need for ongoing development and evaluation of funding models to identify optimal strategies to improve the value and outcomes of hip fracture care. Open Science Framework ( https://osf.io/2938h/ ); first posted 13 June 2022.

Efficacy and safety of restrictive versus liberal blood transfusion strategies in acute myocardial infarction and anemia: a systematic review and meta-analysis of randomized controlled trials.

Blood transfusion strategies in patients with acute myocardial infarction (AMI) and anemia are yet to be conclusively identified. Thus, we aim to assess the efficacy and safety of restrictive versus liberal blood transfusion strategies for AMI and anemia. A systematic review and meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed, web of science, SCOPUS, EMBASE, and Cochrane Central Register of Controlled Trials were performed through November 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). (PROSPERO): ID: CRD42023490692. We included four RCTs with 4.325 patients. There was no significant difference between both groups regarding MACE whether at 30 days (RR: 0.93 with 95% CI [0.57-1.51], P = 0.76) or ≥ six months (RR: 1.17 with 95% CI [0.95-1.45], P = 0.14), all-cause mortality at 30 days (RR: 1.16 with 95% CI [0.95-1.40], P = 0.14) or ≥ six months (RR: 1.16 with 95% CI [0.88-1.53], P = 0.28). However, the liberal strategy was significantly associated with increased hemoglobin level change (MD: -1.44 with 95% CI [-1.68 to -1.20], P < 0.00001). However, the restrictive strategy was significantly associated with a lower incidence of acute lung injury (RR: 0.11 with 95% CI [0.02-0.60], P = 0.01). There was no significant difference between the restrictive blood transfusion strategy and the liberal blood transfusion strategy regarding the clinical outcomes. However, restrictive blood transfusion strategy was significantly associated with a lower incidence of acute lung injury than liberal blood transfusion strategy.

Leptin, Nesfatin-1, Orexin-A, and Total Ghrelin Levels in Drug-Naive Panic Disorder.

This study aimed to examine the changes in serum nesfatin-1, leptin, orexin-A, and total ghrelin levels of patients diagnosed with drug-naive panic disorder (PD) before and after six weeks of the treatment and to compare the findings with the healthy subjects. The neuropeptides were measured in venous blood samples taken from 32 patients and 32 healthy subjects. The blood samples of the patients who used paroxetine 20 mg/day plus alprazolam 0.5 mg/day were retaken again after six weeks. Measurements were performed with the Enzyme-Linked Immunosorbent Assay (ELISA) method. Serum nesfatin-1, leptin, orexin-A and total ghrelin levels of the patient group were found to be significantly lower than the control group (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). When the serum nesfatin-1, leptin, orexin-A and total ghrelin levels of the patient group were compared before and after treatment, significant differences were found in terms of orexin-A and total ghrelin levels (p=0.046, p<0.001, respectively). However, no significant differences were found in terms of nesfatin-1and leptin levels (p=0.205, p=0.988, respectively). This study reports that PD, like other anxiety disorders, may affect serum nesfatin-1, leptin, orexin-A, and total ghrelin levels, and there may be a relationship between PD treatment and the levels of these neuropeptides. The variability of this relationship among the neuropeptides examined indicates that various factors other than treatment play a role in this process.

Dynamics of N6-methyladenosine modification during Alzheimer's disease development

N6-methyladenosine (m6A) modification is a common RNA modification in the central nervous system and has been linked to various neurological disorders, including Alzheimer's disease (AD). However, the dynamic of mRNA m6A modification and m6A enzymes during the development of AD are not well understood. Therefore, this study examined the expression profiles of m6A and its enzymes in the development of AD. The results showed that changes in the expression levels of m6A regulatory factors occur in the early stages of AD, indicating a potential role for m6A modification in the onset of the disease. Additionally, the analysis of mRNA m6A expression profiles using m6A-seq revealed significant differences in m6A modification between AD and control brains. The genes with differential methylation were found to be enriched in GO and KEGG terms related to processes such as inflammation response, immune system processes. And the differently expressed genes (DEGs) are negatively lryassociated with genes involved in microglia hemostasis, but positively associated with genes related to “disease-associated microglia” (DAM) associated genes. These findings suggest that dysregulation of mRNA m6A modification may contribute to the development of AD by affecting the function and gene expression of microglia.

Pparα activation stimulates autophagic flux through lipid catabolism-independent route.

Autophagy is a cellular process that involves the fusion of autophagosomes and lysosomes to degrade damaged proteins or organelles. Triglycerides are hydrolyzed by autophagy, releasing fatty acids for energy through mitochondrial fatty acid oxidation (FAO). Inhibited mitochondrial FAO induces autophagy, establishing a crosstalk between lipid catabolism and autophagy. Peroxisome proliferator-activated receptor α (PPARα), a transcription factor, stimulates lipid catabolism genes, including fatty acid transport and mitochondrial FAO, while also inducing autophagy through transcriptional regulation of transcription factor EB (TFEB). Therefore, the study explores whether PPARα regulates autophagy through TFEB transcriptional control or mitochondrial FAO. In aquaculture, addressing liver lipid accumulation in fish is crucial. Investigating the link between lipid catabolism and autophagy is significant for devising lipid-lowering strategies and maintaining fish health. The present study investigated the impact of dietary fenofibrate and L-carnitine on autophagy by activating Pparα and enhancing FAO in Nile tilapia (Oreochromis niloticus), respectively. The dietary fenofibrate and L-carnitine reduced liver lipid content and enhanced ATP production, particularly fenofibrate. FAO enhancement by L-carnitine showed no changes in autophagic protein levels and autophagic flux. Moreover, fenofibrate-activated Pparα promoted the expression and nuclear translocation of Tfeb, upregulating autophagic initiation and lysosomal biogenesis genes. Pparα activation exhibited an increasing trend of LC3II protein at the basal autophagy and cumulative p62 protein trends after autophagy inhibition in zebrafish liver cells. These data show that Pparα activation-induced autophagic flux should be independent of lipid catabolism.

A new methodology to reveal potential nucleic acid modifications associated with the risk of endometrial cancer through dispersive solid-phase extraction coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC-UV.

Nucleic acid modifications have attracted increasing attention in recent years since they have been found to be related to a number of diseases including cancer. Previous studies have shown that the early development of endometrial cancer (EC) is often accompanied by changes in methylation levels of related genes, and the expression of related proteins that regulate reactive oxygen species (ROS) shows significant differences in EC cells and tissues. However, it has not been reported whether nucleic acid modifications related to methylation or ROS can serve as biomarkers for EC. Accurate quantification of these nucleic acid modifications still has challenges because their amounts in urine are very low and the interferences in urine are complicated. In this study, a novel dispersive solid-phase extraction (DSPE) method based on chitosan-carbon nanotube-Al2O3 (CS-CNT-Al2O3) has been established for the analysis of 5-hydroxymethyluracil (5mU), 5-methyl-2'-deoxycytidine (5-mdC), 5-hydroxymethyl-2'-deoxycytidine (5-hmdC), 5-formyl-2'-deoxycytidine (5-fdC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in EC patient urine samples coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC-UV. Firstly, the synthesis of the CS-CNT-Al2O3 nanocomposite was conducted by a sono-coprecipitation method and was characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), and Fourier transform infrared (FTIR). Under the optimal extraction conditions of DSPE, we successfully quantified 5mU, 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in urine samples from 37 EC patients and 39 healthy controls. The results showed that there were significant differences in the levels of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in EC patients compared to the healthy control group. The receiver operator characteristic (ROC) curve analysis was carried out to evaluate the potential of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG to distinguish EC patients from healthy volunteers. The area under the curve (AUC) for 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG was 0.7412, 0.667, 0.8438, and 0.7981, respectively. It indicated that 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG had certain potential in distinguishing between EC patients and healthy volunteers and they could act as potential non-invasive biomarkers for early diagnosis of EC. Moreover, the present study would stimulate investigations of the effects of nucleic acid modifications on the initiation and progression of EC.