Pediatric Sedation Assessment and Management System (PSAMS) for Pediatric Sedation in China: Development and Implementation Report.

Background: Recently, the growing demand for pediatric sedation services outside the operating room has imposed a heavy burden on pediatric centers in China. There is an urgent need to develop a novel system for improved sedation services. Objective: This study aimed to develop and implement a computerized system, the Pediatric Sedation Assessment and Management System (PSAMS), to streamline pediatric sedation services at a major children's hospital in Southwest China. Methods: PSAMS was designed to reflect the actual workflow of pediatric sedation. It consists of 3 main components: server-hosted software; client applications on tablets and computers; and specialized devices like gun-type scanners, desktop label printers, and pulse oximeters. With the participation of a multidisciplinary team, PSAMS was developed and refined during its application in the sedation process. This study analyzed data from the first 2 years after the system's deployment. Unlabelled: From January 2020 to December 2021, a total of 127,325 sedations were performed on 85,281 patients using the PSAMS database. Besides basic variables imported from Hospital Information Systems (HIS), the PSAMS database currently contains 33 additional variables that capture comprehensive information from presedation assessment to postprocedural recovery. The recorded data from PSAMS indicates a one-time sedation success rate of 97.1% (50,752/52,282) in 2020 and 97.5% (73,184/75,043) in 2021. The observed adverse events rate was 3.5% (95% CI 3.4%-3.7%) in 2020 and 2.8% (95% CI 2.7%-2.9%) in 2021. Conclusions: PSAMS streamlined the entire sedation workflow, reduced the burden of data collection, and laid a foundation for future cooperation of multiple pediatric health care centers.

Advances in the selection of functional monomers for molecularly imprinted polymers: A review.

Molecularly imprinted polymers, a type of special polymer materials, are widely used in biosensing and other fields due to their ability to specifically recognize target molecules, often called "artificial receptors.". Nowadays, researchers are constantly exploring new design and synthesis methods for molecularly imprinted materials to improve the selectivity and sensitivity of molecularly imprinted materials. Among them, the selection of functional monomers has attracted great attention. This review comprehensively analyzes and discusses the selection methods of functional monomers. The most commonly used functional monomers among different types of templates are screened based on the structural properties of the template molecules, including the selection of functional monomers among ion-imprinted polymers, protein-imprinted polymers, and bacterial imprinted polymers. The rich binding sites and functional group types of multifunctional monomers are also highlighted to advance the development of molecular imprinting technology. The article further explores the current challenges and prospects in the selection of functional monomers and emphasizes multiplex experiments and computer simulations as important directions for future research. This review provides comprehensive information and constructive guidelines for researchers in selecting functional monomers in areas such as analytical chemistry and biosensors.

Rotavirus vaccination is a protective factor for adverse outcomes in primary intussusception: a single-center retrospective study.

Background: The clinical features and prognosis of intussusception in children vaccinated against rotavirus were undefined. Hence, we conducted the study to explore the clinical characteristics and outcomes of primary intussusception patients who received rotavirus vaccine. Methods: A single-center retrospective study was performed in 327 primary intussusception patients between January 2019 and December 2021. Of these, 168 were vaccinated against rotavirus and 159 were not, the latter serving as the control group. Data on patients' clinical characteristics, commonly used inflammatory biomarkers, treatment, and outcomes were collected and evaluated. Results: Most of the vaccination group received pentavalent rotavirus vaccine produced by Merck, USA (89.88%). There were no differences in demographic characteristics, time from onset to hospital attendance, clinical symptoms and signs between the vaccination group and the control group. The success rate of air enema reduction in the vaccination group was higher than that in the control group (98.21% vs. 88.68%, q=0.01). The vaccination group had lower rates of surgery and complication (1.79% vs. 11.32%, q=0.008; 2.98% vs. 12.58%, q=0.006). Both platelet-lymphocyte ratio (PLR) and C-reactive protein (CRP) levels were lower in the vaccinated group (q=0.02, q=0.004). Higher CRP level [odds ratio (OR): 1.635; 95% confidence interval (CI): 1.248-2.143; P=0.006] and the longer time from onset to hospital attendance (OR: 3.040; 95% CI: 2.418-12.133; P=0.01) were associated with increased adverse events. Rotavirus vaccination (OR: 0.527; 95% CI: 0.103-0.751; P=0.02) was associated with a reduction in the probability of adverse events. Conclusions: Adverse events such as surgery and complications were lower in the vaccination group. Rotavirus vaccination was an independent protective factor for adverse events in patients with primary intussusception.

Dietary curcumin supplementation attenuates hepatic damage and function abnormality in a chronic corticosterone-induced stress model in broilers.

Chronic stress refers to the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated blood contents of ACTH and corticosterone (CORT), exhibiting significant adverse effects on health outcomes. Currently, natural polyphenol compounds are increasingly being explored as potential therapeutic agents and have been considered as a treatment option for a variety of stress-induced diseases. Curcumin (CUR) is the main substance in Curcuma longa (Zingiberacea) rhizome that has strong health-beneficial properties. The study aimed to assess the potential protective effects of CUR on hepatic oxidative stress damage and abnormal lipid deposition in a chronic CORT-induced stress (CCIS) model in broilers. One hundred and twenty experimental broilers were randomly divided into 1) control group (CON), 2) CUR group (200 mg/kg feed), 3) CORT group (4 mg/kg BW CORT) and 4) CORT+CUR group (200 mg/kg feed plus 4 mg/kg BW CORT). The liver histology, glycolipid metabolism and oxidative stress were determined. In addition, qPCR was performed to identify shifts in genes expression. Compared with CON group, broilers under CCIS showed a decreased body weight, body weight gain and average daily gain, while dietary CUR significantly reversed these adverse effects. Furthermore, the plasma contents of TCH, TG, HDL-C, LDL-C, TP, GLB and AST were all significantly increased in CCIS broilers, while dietary CUR obviously alleviated the increase of TCH, HDL-C, LDL-C and AST, and relieved the hepatic lipid deposition disorder and liver injury. Moreover, CCIS significantly increased the contents of MDA in both liver and plasma, and decreased the content of plasma SOD, while CUR obviously reversed these changes, showing reduced oxidative stress damage. Finally, the mRNA expressions of FAS, ACC, SCD and the protein level of PPAR-γ were significantly increased, meanwhile the mRNA expression of lipolytic genes ACOX1, ATGL and CPT as well as two major intracellular antioxidant enzymes SOD1 and GPX1 were obviously decreased, while CUR effectively reversed these effects. These results showed that dietary CUR effectively alleviated CCIS-induced body weight loss, hepatic oxidative damage and lipid deposition disorder, suggesting the possible therapeutic effectiveness of CUR against hepatic damage and function abnormality caused by CCIS.

Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats.

BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. METHODS: This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin-angiotensin-aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. RESULTS: At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. CONCLUSIONS: Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances.

Serum matrix metalloproteinase-7 for discriminating biliary atresia: a diagnostic accuracy and validation study.

BACKGROUND: Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients. METHODS: This was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA). RESULTS: The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946-0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5-97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0-90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9-93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6-96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0-30 days, which was 86.4% (95% CI: 75.0-94.0%), 95.5% (95% CI: 77.2-99.9%), 98.1% (95% CI: 89.7-100%), and 72.4% (95% CI: 52.8-87.3%), respectively. CONCLUSIONS: The serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.

The mutual longitudinal mediating effects of psychological and physical disorders on cognitive impairment among older adults.

BACKGROUND: The potential mutual effect of physical and psychological disorders on cognitive function is critical for preventing cognitive impairment among older adults. We aimed to investigate the mediating role of physical and psychological disorders in their associations with cognitive function. METHODS: We conducted a prospective cohort study using the Health and Retirement Study, involving 5308 adults aged 60 years or older. Physical disorders included seven self-reported physician-diagnosed conditions. Psychological disorder and cognitive function were ascertained using the 8-item Centers for Epidemiologic Research Depression scale and the 27-point HRS cognitive scale, respectively. Multivariable linear regression models were used to assess the association of the baseline scores of physical and psychological disorders with subsequent cognitive scores. Second-order cross-lagged panel models (CLPM) were used to assess the longitudinal mediating roles, respectively. RESULTS: The higher psychological disorder scores (ß = -0.15; P < 0.0001) and physical disorders scores (ß = -0.18; P < 0.0001) were, the worse the cognitive function was. CLPM revealed a significant longitudinal mediating effect of baseline physical disorders through changes in psychological disorder from 2002 to 2010 on the cognitive scores changes from 2002 to 2010 (ß = -0.02; P < 0.0001). Meanwhile, the longitudinal mediating effect of baseline psychological disorder scores through physical disorders changes from 2002 to 2010 on the cognitive scores changes from 2002 to 2010 was significant (ß = -0.004; P = 0.005). CONCLUSIONS: The mutual longitudinal mediating effects of psychological disorder and physical disorder indicate that among older adults, physical and psychological disorders accelerate cognitive impairment as a whole and mutually reinforcing process.

AMPK Deficiency Increases DNA Methylation and Aggravates Colorectal Tumorigenesis in AOM/DSS Mice.

The incidence of colorectal cancer (CRC) is closely linked to metabolic diseases. Accumulating evidence suggests the regulatory role of AMP-activated protein kinase (AMPK) in cancer metabolic reprogramming. In this study, wild-type and AMPK knockout mice were subjected to azoxymethane-induced and dextran sulfate sodium (AOM/DSS)-promoted colitis-associated CRC induction. A stable AMPK-deficient Caco-2 cell line was also established for the mechanistic studies. The data showed that AMPK deficiency accelerated CRC development, characterized by increased tumor number, tumor size, and hyperplasia in AOM/DSS-treated mice. The aggravated colorectal tumorigenesis resulting from AMPK ablation was associated with reduced α-ketoglutarate production and ten-eleven translocation hydroxylase 2 (TET2) transcription, correlated with the reduced mismatch repair protein mutL homolog 1 (MLH1) protein. Furthermore, in AMPK-deficient Caco-2 cells, the mRNA expression of mismatch repair and tumor suppressor genes, intracellular α-ketoglutarate, and the protein level of TET2 were also downregulated. AMPK deficiency also increased hypermethylation in the CpG islands of Mlh1 in both colonic tissues and Caco-2 cells. In conclusion, AMPK deficiency leads to reduced α-ketoglutarate concentration and elevates the suppressive epigenetic modifications of tumor suppressor genes in gut epithelial cells, thereby increasing the risk of colorectal tumorigenesis. Given the modifiable nature of AMPK activity, it holds promise as a prospective molecular target for the prevention and treatment of CRC.

Armillariella tabescens-derived polysaccharides alleviated â±°-Gal-induced neuroinflammation and cognitive injury through enterocerebral axis and activation of keap-1/Nrf2 pathway.

The early symptoms of neurodegenerative diseases include oxidative stress disorder and accelerated inflammation levels. Edible fungi polysaccharides play essential roles in anti-neuroinflammation. We analyzed the regulatory mechanisms of polysaccharides from extracellular Armillariella tabescens (ATEP) in alleviating neuroinflammation in mice. Mice were induced with d-galactose and aluminum chloride to establish an animal model of Alzheimer's disease, then intragastrically treated with ATEP, which had been previously analyzed for its physicochemical properties. We assessed the critical characteristics of mice treated for neuroinflammation, including cognitive behavior, the anti-inflammatory potential of ATEP in hippocampal pathology and critical protein expression, and changes in fecal microbial composition and metabolites. ATEP intervened in oxidative stress by enhancing antioxidant enzyme activities and suppressing the Keap-1/Nrf2 signaling pathway. Changing the Nrf2 content in the nucleus led to changes in the downstream oxidation-related enzymes, HO-1, NQO-1, iNOS, and COX-2, and the neuronal morphology in CA3 region of the hippocampus. Microbiome analysis revealed that ATEP remodeled the gut microbiotas and regulated the short-chain fatty acids-producing bacteria. Early intervention with ATEP via active dietary supplementation may promote neuroprotection.

Discovery of a class of glycosaminoglycan lyases with ultrabroad substrate spectrum and their substrate structure preferences.

Glycosaminoglycan (GAG) lyases are often strictly substrate specific, and it is especially difficult to simultaneously degrade GAGs with different types of glycosidic bonds. Herein, we found a new class of GAG lyases (GAGases) from different bacteria. These GAGases belong to polysaccharide lyase 35 family and share quite low homology with the identified GAG lyases. The most surprising thing is that GAGases can not only degrade three types of GAGs: hyaluronan, chondroitin sulfate, and heparan sulfate but also even one of them can also degrade alginate. Further investigation of structural preferences revealed that GAGases selectively act on GAG domains composed of non/6-O-/N-sulfated hexosamines and d-glucoronic acids as well as on alginate domains composed of d-mannuronic acids. In addition, GAG lyases were once speculated to have evolved from alginate lyases, but no transitional enzymes have been found. The discovery of GAGases not only broadens the category of GAG lyases, provides new enzymatic tools for the structural and functional studies of GAGs with specific structures, but also provides candidates for the evolution of GAG lyases.

Predicting brain edema and outcomes after thrombectomy in stroke: Frontal delta/alpha ratio as an optimal quantitative EEG index.

OBJECTIVE: We aimed to determine whether quantitative electroencephalography (QEEG) measures have predictive value for cerebral edema (CED) and clinical outcomes in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion who underwent mechanical thrombectomy (MT). METHODS: A total of 105 patients with AIS in the anterior circulation were enrolled in this prospective study. The occurrence and severity of CED were assessed through computed tomography conducted 24 h after MT. Clinical outcomes were evaluated based on early neurological deterioration (END) and 3-month functional status, as measured by the modified Rankin scale (mRS). Electroencephalography (EEG) recordings were performed 24 h after MT, and QEEG indices were calculated from the standard 16 electrodes and 2 frontal channels (F3-C3, F4-C4). The delta/alpha ratio (DAR), the (delta + theta) / (alpha + beta) ratio (DTABR), and relative delta power were averaged over all electrodes (global) and the F3-C3 and F4-C4 channels (frontal). The predictive effect and value of QEEG indices for CED and clinical outcomes were assessed using ordinal and logistic regression models, as well as receiver operating characteristic (ROC) curves. RESULTS: Significantly, both global and frontal DAR were found to be associated with the severity of CED, END, and poor functional outcomes at 90 days, while global and frontal DTABR and relative delta power were not associated with outcomes. In ROC analysis, the best predictive effect was observed in frontal DAR, with an area under the curve of approximately 0.80. It exhibited approximately 75% sensitivity and 71% specificity for radiological and clinical outcomes when a threshold of 3.3 was used. CONCLUSIONS: QEEG techniques may be considered an efficient bedside monitoring method for assessing treatment efficacy, identifying patients at higher risk of severe CED and END, and predicting long-term functional outcomes. SIGNIFICANCE: QEEG can help identify patients at risk of severe neurological complications that can impact long-term functional recovery in AIS patients who underwent MT.

Differences in Metabolite Profiles of Dihydroberberine and Micellar Berberine in Caco-2 Cells and Humans-A Pilot Study.

We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group-except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials.

A Comparison and Safety Evaluation of Micellar versus Standard Vitamin D3 Oral Supplementation in a Randomized, Double-Blind Human Pilot Study.

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D3 formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D3 1000 IU (STD1000), (2) micellar Vitamin D3 1000 IU (LMD1000), (3) standard Vitamin D3 2500 IU (STD2500), and (4) micellar Vitamin D3 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5-60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D3 absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D3 concentrations than the STD1000 group (iAUC(30-60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)2D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D3 (LipoMicel®), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.

Burden and trends of infectious disease mortality attributed to air pollution, unsafe water, sanitation, and hygiene, and non-optimal temperature globally and in different socio-demographic index regions.

BACKGROUND: Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019. METHODS: This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019. RESULTS: In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65-69, 75-79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature. CONCLUSIONS: Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.

Evaluation of the Metabolite Profile of Fish Oil Omega-3 Fatty Acids (n-3 FAs) in Micellar and Enteric-Coated Forms-A Randomized, Cross-Over Human Study.

This study evaluated the differences in the metabolite profile of three n-3 FA fish oil formulations in 12 healthy participants: (1) standard softgels (STD) providing 600 mg n-3 FA; (2) enteric-coated softgels (ENT) providing 600 mg n-3 FA; (3) a new micellar formulation (LMF) providing 374 mg n-3 FA. The pharmacokinetics (PKs), such as the area under the plot of plasma concentration (AUC), and the peak blood concentration (Cmax) of the different FA metabolites including HDHAs, HETEs, HEPEs, RvD1, RvD5, RvE1, and RvE2, were determined over a total period of 24 h. Blood concentrations of EPA (26,920.0 ± 10,021.0 ng/mL·h) were significantly higher with respect to AUC0-24 following LMF treatment vs STD and ENT; when measured incrementally, blood concentrations of total n-3 FAs (EPA/DHA/DPA3) up to 11 times higher were observed for LMF vs STD (iAUC 0-24: 16,150.0 ± 5454.0 vs 1498.9 ± 443.0; p ≤ 0.0001). Significant differences in n-3 metabolites including oxylipins were found between STD and LMF with respect to 12-HEPE, 9-HEPE, 12-HETE, and RvD1; 9-HEPE levels were significantly higher following the STD vs. ENT treatment. Furthermore, within the scope of this study, changes in blood lipid levels (i.e., cholesterol, triglycerides, LDL, and HDL) were monitored in participants for up to 120 h post-treatment; a significant decrease in serum triglycerides was detected in participants (~20%) following the LMF treatment; no significant deviations from the baseline were detected for all the other lipid biomarkers in any of the treatment groups. Despite a lower administered dose, LMF provided higher blood concentrations of n-3 FAs and certain anti-inflammatory n-3 metabolites in human participants-potentially leading to better health outcomes.

Roles of Pseudomonas aeruginosa siderophores in interaction with prokaryotic and eukaryotic organisms.

Pseudomonas aeruginosa is an opportunistic pathogen that produces two types of siderophores, pyoverdine and pyochelin, that play pivotal roles in iron scavenging from the environment and host cells. P. aeruginosa siderophores can serve as virulence factors and perform various functions. Several bacterial and fungal species are likely to interact with P. aeruginosa due to its ubiquity in soil and water as well as its potential to cause infections in plants, animals, and humans. Siderophores produced by P. aeruginosa play critical roles in iron scavenging for prokaryotic species (bacteria) and eukaryotic hosts (fungi, animals, insects, invertebrates, and plants) as well. This review provides a comprehensive discussion of the role of P. aeruginosa siderophores in interaction with prokaryotes and eukaryotes as well as their underlying mechanisms of action. The evolutionary relationship between P. aeruginosa siderophore recognition receptors, such as FpvA, FpvB, and FptA, and those of other bacterial species has also been investigated.

Global, regional and national trends and impacts of natural floods, 1990-2022.

Objective: To assess global, regional and national trends in the impact of floods from 1990 to 2022 and determine factors influencing flood-related deaths. Methods: We used data on flood disasters from the International Disaster Database for 1990-2022 from 168 countries. We calculated the annual percentage change to estimate trends in the rates of people affected and killed by floods by study period, World Health Organization (WHO) region, country income level and flood type. We used multivariable logistic regression analysis to assess the factors associated with death from floods. Findings: From 1990 to 2022, 4713 floods were recorded in 168 countries, which affected > 3.2 billion people, caused 218 353 deaths and were responsible for more than 1.3 trillion United States dollars of economic losses. The WHO Western Pacific Region had the most people affected by floods (> 2.0 billion), accounting for 63.19% (2 024 599 380/3 203 944 965) of all affected populations. The South-East Asia Region had the most deaths (71 713, 32.84%). The African and Eastern Mediterranean Regions had the highest number of people affected and killed by floods per 100 000 population in 2022. The odds of floods causing more than 50 deaths were significantly higher in low-income countries (adjusted odds ratio: 14.34; 95% confidence interval: 7.46 to 30.04) compared with high-income countries. Numbers of people affected and mortality due to floods declined over time. Conclusion: Despite the decreases in populations affected and deaths, floods still have a serious impact on people and economies globally, particularly in lower-income countries. Action is needed to improve disaster risk management and flood mitigation.

Inhibition of BMP-mediated SMAD pathway supports the pluripotency of pig embryonic stem cells in the absence of feeder cells.

Here, we examined the effects of the BMP signaling pathway inhibitor LDN-193189 on the pluripotency of porcine embryonic stem cells (ESCs) in the absence of feeder cells using molecular and transcriptomic techniques. Additionally, the effects of some extracellular matrix components on porcine ESC pluripotency were evaluated to develop an optimized and sustainable feeder-free culture system for porcine ESCs. Feeder cells were found to play an important role in supporting the pluripotency of porcine ESCs by blocking trophoblast and mesodermal differentiation through the inhibition of the BMP pathway. Additionally, treatment with LDN-193189, an inhibitor of the BMP pathway, maintained the pluripotency and homogeneity of porcine ESCs for an extended period in the absence of feeder cells by stimulating the secretion of chemokines and suppressing differentiation, based on transcriptome analysis. Conclusively, these results suggest that LDN-193189 could be a suitable replacement for feeder cells in the maintenance of porcine ESC pluripotency during culture. Additionally, these findings contribute to the understanding of pluripotency gene networks and comparative embryogenesis.

Study on mechanism underlying the acceleration of pitting corrosion of B30 copper-nickel alloy by sulfate-reducing bacteria in seawater.

In this paper, the relationship between the pitting corrosion formation of B30 copper-nickel (CuNi) alloy and the metabolism of sulfate-reducing bacteria (SRB) was investigated. Combined with the influence of temperature during the actual operation of the cooling systems, the evolution law of the alloy passivation film was analyzed, and the mechanism of SRB promoting the accelerated development of B30 CuNi alloy pitting corrosion was revealed. The results show that SRB significantly promoted the pitting formation and development of B30 CuNi alloy. The maximum pitting depth was 3.9 µm in the sterile system and 15.3 µm with SRB, which was 3.9 times higher than that of sterile system. The loose porous Cu2S film formed by SRB metabolites and copper matrix was easily penetrated by corrosive anions, which promoted copper dissolution and led to pit nucleation. The sulfide adsorbed on the surface prevented or delayed the passivation of B30 CuNi alloy by blocking the adsorption site of O atom, and the corrosion nuclei continued to grow. The non-uniformity caused by the film peeling accelerated the longitudinal development of pitting corrosion, and the expansion and coalescence of adjacent pits caused the transverse development of pitting corrosion. Temperature had a certain influence on the SRB and the formation of B30 CuNi alloy passivation film. The passivation film was formed rapidly at 50 °C with poor quality and the passivation property of Cu2O film was weakened. With the increase of temperature, the pitting potential of sterile system negative shifted from 0.447 to 0.360 V (vs. SCE), while SRB system from 0.340 to 0.198 V (vs. SCE), and the pitting resistance decreased. The passivation film with defects and the Cu2S reduced the barrier efficiency of the film and accelerated the pitting corrosion of B30 CuNi alloy.