Enhancement of the function of mesenchymal stem cells by using a GMP-grade three-dimensional hypoxic large-scale production system.

Background: Efficiently increasing the production of clinical-grade mesenchymal stem cells (MSCs) is crucial for clinical applications. Challenges with the current planar culture methods include scalability issues, labour intensity, concerns related to cell senescence, and heterogeneous responses. This study aimed to establish a large-scale production system for MSC generation. In addition, a comparative analysis of the biological differences between MSCs cultured under various conditions was conducted. Methods and materials: We developed a GMP-grade three-dimensional hypoxic large-scale production (TDHLSP) system for MSCs using self-fabricated glass microcarriers and a multifunctional bioreactor. Different parameters, including cell viability, cell diameter, immunophenotype, morphology, karyotype, and tumourigenicity were assessed in MSCs cultured using different methods. Single-cell RNA sequencing (scRNA-seq) revealed pathways and genes associated with the enhanced functionality of MSCs cultured in three dimensions under hypoxic conditions (3D_Hypo MSCs). Moreover, CD142 knockdown in 3D_Hypo MSCs confirmed its in vitro functions. Results: Inoculating 2 × 108 MSCs into a 2.6 L bioreactor in the TDHLSP system resulted in a final scale of 4.6 × 109 3D_Hypo MSCs by day 10. The 3D_Hypo MSCs retained characteristics of the 2D MSCs, demonstrating their genomic stability and non-tumourigenicity. Interestingly, the subpopulations of 3D_Hypo MSCs exhibited a more uniform distribution and a closer relationship than those of 2D MSCs. The heterogeneity of MSCs was strongly correlated with 'cell cycle' and 'stroma/mesenchyme', with 3D_Hypo MSCs expressing higher levels of activated stroma genes. Compared to 2D MSCs, 3D_Hypo MSCs demonstrated enhanced capabilities in blood vessel formation, TGF-ß1 secretion, and inhibition of BV2 proliferation, with maintenance of Senescence-Associated ß-Galactosidase (SA-ß-gal) negativity. However, the enhanced functions of 3D_Hypo MSCs decreased upon the downregulation of CD142 expression. Conclusion: The TDHLSP system led to a high overall production of MSCs and promoted uniform distribution of MSC clusters. This cultivation method also enhanced key cellular properties, such as angiogenesis, immunosuppression, and anti-aging. These functionally improved and uniform MSC subpopulations provide a solid basis for the clinical application of stem cell therapies.

Widespread and active piezotolerant microorganisms mediate phenolic compound degradation under high hydrostatic pressure in hadal trenches.

Phenolic compounds, as well as other aromatic compounds, have been reported to be abundant in hadal trenches. Although high-throughput sequencing studies have hinted at the potential of hadal microbes to degrade these compounds, direct microbiological, genetic and biochemical evidence under in situ pressures remain absent. Here, a microbial consortium and a pure culture of Pseudomonas, newly isolated from Mariana Trench sediments, efficiently degraded phenol under pressures up to 70 and 60 MPa, respectively, with concomitant increase in biomass. By analyzing a high-pressure (70 MPa) culture metatranscriptome, not only was the entire range of metabolic processes under high pressure generated, but also genes encoding complete phenol degradation via ortho- and meta-cleavage pathways were revealed. The isolate of Pseudomonas also contained genes encoding the complete degradation pathway. Six transcribed genes (dmpKLMNOPsed) were functionally identified to encode a multicomponent hydroxylase catalyzing the hydroxylation of phenol and its methylated derivatives by heterogeneous expression. In addition, key catabolic genes identified in the metatranscriptome of the high-pressure cultures and genomes of bacterial isolates were found to be all widely distributed in 22 published hadal microbial metagenomes. At microbiological, genetic, bioinformatics, and biochemical levels, this study found that microorganisms widely found in hadal trenches were able to effectively drive phenolic compound degradation under high hydrostatic pressures. This information will bridge a knowledge gap concerning the microbial aromatics degradation within hadal trenches. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00224-2.

A fluorescence probe with targeted mitochondria for detecting hydrogen peroxide in vitro and in diabetic mice.

We designed and prepared probe W-1 for the detection of H2O2. W-1 showed excellent selectivity for H2O2 and was accompanied by colorimetric signal changes. The excellent linear relationship between fluorescence intensity and H2O2 concentration (0-100 µM) provided favorable conditions for its quantitative detection. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site visual detection of H2O2. Moreover, W-1 possessed targeting mitochondria property and could be applied to image the exogenous and endogenous H2O2 in cells to distinguish normal cells and cancer cells. Lastly, W-1 was used for monitoring the H2O2 fluctuation of the diabetic process in mice, and the results showed an increase in H2O2 levels in diabetes. Therefore, the probe provided a tool for understanding the pathological and physiological mechanisms of diabetes by imaging H2O2.

The Global Burden of Disease Attributable to Child and Maternal Malnutrition: 1990-2019.

OBJECTIVE: With this study, we aimed to estimate the disease burden attributable to child and maternal malnutrition (CMM) throughout the world between 1990 and 2019. METHODS: The number, age-standardized rate, population attributable fraction of deaths, disability-adjusted life-years, years of life lost, and years lived with disability associated with CMM were estimated using the Global Burden of Disease Study 2019 by age, sex, year, location, and sociodemographic index at the global level. The slope index of inequality and concentration index were employed to measure socioeconomic-related health inequalities across countries. RESULTS: The number (million) of global deaths, disability-adjusted life-years, and years of life lost related to CMM were 2.9, 294.8, and 250.5 in 2019, showing decreases of 60.8, 57.4, and 60.7% since 1990. However, the number of years lived with CMM-related disability increased from 36.0 in 1990 to 44.3 in 2019. Additionally, the age-standardized rates of these 4 indicators showed varying degrees of decline. The global burden of CMM-related conditions differed with age and sex. The burden was the heaviest in western sub-Saharan Africa, especially in Chad. In terms of diseases, neonatal disorders represented the most significant burden attributed to CMM. Additionally, the CMM burden was more concentrated in regions with low sociodemographic indices, shown by the slope index of inequality and concentration index. CONCLUSIONS: The findings of this study highlight the ongoing global burden of CMM, particularly in terms of years lived with disability. Population-wide actions targeting the effective treatment and relief of CMM may reduce the CMM-related disease burden.

Silencing CD28 attenuated chest blast exposure-induced traumatic brain injury through the PI3K/AKT/NF-κB signaling pathway in male mice.

In modern war or daily life, blast-induced traumatic brain injury (bTBI) is a growing health concern. Our previous studies demonstrated that inflammation was one of the main features of bTBI, and CD28-activated T cells play a central role in inflammation. However, the mechanism of CD28 in bTBI remains to be elucidated. In this study, traumatic brain injury model induced by chest blast exposure in male mice was established, and the mechanism of CD28 in bTBI was studied by elisa, immunofluorescence staining, flow cytometry analysis and western blot. After exposure to chest shock wave, the inflammatory factors IL-4, IL-6 and HMGB1 in serum were increased, and CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung were activated. In addition, chest blast exposure resulted in impaired spatial learning and memory ability, disruption of the blood-brain barrier (BBB), and the expression of Tau, p-tau, S100ß and choline acetyltransferase were increased. The results indicated that genetic knockdown of CD28 could inhibit inflammatory cell infiltration, as well as the activation of CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung, improve spatial learning and memory ability, and ameliorate BBB disruption and hippocampal neuron damage. Moreover, genetic knockdown of CD28 could reduce the expression of p-PI3K, p-AKT and NF-κB. In conclusion, chest blast exposure could lead to bTBI, and attenuate bTBI via the PI3K/AKT/NF-κB signaling pathway in male mice. This study provides new targets for the prevention and treatment of veterans with bTBI.

Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.

Advances in targeting histone deacetylase for treatment of solid tumors.

Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention. A variety of HDAC inhibitors (HDACis) have been developed to target HDACs. Many preclinical studies have conclusively demonstrated the antitumor effects of HDACis, whether used as monotherapy or in combination treatments. On this basis, researchers have conducted various clinical studies to evaluate the potential of selective and pan-HDACis in clinical settings. In our work, we extensively summarized and organized current clinical trials, providing a comprehensive overview of the current clinical advancements in targeting HDAC therapy. Furthermore, we engaged in discussions about several clinical trials that did not yield positive outcomes, analyzing the factors that led to their lack of anticipated therapeutic effectiveness. Apart from the experimental design factors, issues such as toxicological side effects, tumor heterogeneity, and unexpected off-target effects also contributed to these less-than-expected results. These challenges have naturally become significant barriers to the application of HDACis. Despite these challenges, we believe that advancements in HDACi research and improvements in combination therapies will pave the way or lead to a broad and hopeful future in the treatment of solid tumors.

Association between depressive symptoms and cognitive function in the older population, and the mediating role of neurofilament light chain: Evidence from NHANES 2013-2014.

OBJECTIVE: This study aimed to investigate the potential mediating role of the neurofilament light chain (NfL) level between depressive symptoms and cognitive function in older population. METHODS: A total of 495 adults (age ≥60 years) from the National Health and Nutrition Examination Survey (NHANES) participated in this study. Cognitive function was assessed using a combination of the Animal Fluency Test (AFT), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and the Digit Symbol Substitution Test (DSST). Word List Learning Test. Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. Data on serum NfL(sNfL) were collected. Multiple linear regressions and mediation analysis were utilized to examine the associations. RESULTS: After adjusting for potential confounding factors, the proportions mediated by the sNfL level between depressive symptoms and cognitive function was 19.65 %. The indirect effect mediated by the sNfL level between depressive symptoms and cognitive function was significant (ß[95 % CI]:-0.0089 [-0.0191, -0.0017],p = 0.040), while the direct effect in the absence of sNfL was non-significant (ß[95 % CI]: -0.0365 [-0.0739 0.0008],p = 0.055). LIMITATIONS: This is an explorative cross-sectional study with its limits in generalizability and ability to establish definitive causal associations. The results should be interpreted with caution due to the constraints imposed by the characteristics of the population with a relatively low overall level of depressive symptoms. CONCLUSION: The sNfL level, depressive symptoms, and cognitive decline are interconnected, and the sNfL level could mediate the relationship between depressive symptoms and cognitive decline among older adults.

Elemental diet preventative effects for adverse events during chemotherapy in patients with esophageal cancer - A systematic review and meta-analysis.

The effectiveness of an elemental diet (ED) for preventing adverse events (AEs) during chemotherapy for patients with esophageal cancer (EC) remains unclear. The aim of this meta-analysis was to comprehensively assess the efficacy of ED for preventing AE in EC patients during chemotherapy. Medline (via PubMed), Embase, the Cochrane Library, and Web of Science were searched to retrieve prospective and randomized studies published before April 12, 2023. The odds ratio (OR) of each AE was calculated using Review Manger 5.4.1. The risk of bias was assessed, and a random effect model-based meta-analysis was used to analyze the available data. Four prospective and randomized studies involving 237 patients were identified after a systematic search. Regarding gastrointestinal toxicities, the findings indicated a trend toward a decrease in the risk of mucositis (OM) (OR = 0.54, 95 % CI: 0.25-1.14), constipation (OR = 0.87, 95 % CI: 0.49-1.53), and anorexia (OR = 0.99, 95 % CI: 0.32-3.05), as well as an increasing trend in the risk of diarrhea (OR = 1.48, 95 % CI: 0.79-2.79), among patients treated with ED. However, none of these reached statistical significance. For hematological toxicities, the risk of all-grade neutropenia (OR = 0.28, 95 % CI: 0.14-0.57), grade ≥ 2 leucopenia (OR = 0.43, 95 % CI: 0.22-0.84), grade ≥ 2 neutropenia (OR = 0.34, 95 % CI: 0.17-0.67), and grade ≥ 3 neutropenia (OR = 0.28, 95 % CI: 0.12-0.63) was significantly decreased. There is no firm evidence confirming the preventive effect of an ED against OM or diarrhea. However, an ED may potentially be helpful in preventing neutropenia and leucopenia.

Zeaxanthin dipalmitate-enriched wolfberry extract improves vision in a mouse model of photoreceptor degeneration.

Zeaxanthin dipalmitate (ZD) is a chemical extracted from wolfberry that protects degenerated photoreceptors in mouse retina. However, the pure ZD is expensive and hard to produce. In this study, we developed a method to enrich ZD from wolfberry on a production line and examined whether it may also protect the degenerated mouse retina. The ZD-enriched wolfberry extract (ZDE) was extracted from wolfberry by organic solvent method, and the concentration of ZD was identified by HPLC. The adult C57BL/6 mice were treated with ZDE or solvent by daily gavage for 2 weeks, at the end of the first week the animals were intraperitoneally injected with N-methyl-N-nitrosourea to induce photoreceptor degeneration. Then optomotor, electroretinogram, and immunostaining were used to test the visual behavior, retinal light responses, and structure. The final ZDE product contained ~30mg/g ZD, which was over 9 times higher than that from the dry fruit of wolfberry. Feeding degenerated mice with ZDE significantly improved the survival of photoreceptors, enhanced the retinal light responses and the visual acuity. Therefore, our ZDE product successfully alleviated retinal morphological and functional degeneration in mouse retina, which may provide a basis for further animal studies for possible applying ZDE as a supplement to treat degenerated photoreceptor in the clinic.

Discovery of LC-MI-3: A Potent and Orally Bioavailable Degrader of Interleukin-1 Receptor-Associated Kinase 4 for the Treatment of Inflammatory Diseases.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a promising therapeutic target in inflammation-related diseases. However, the inhibition of IRAK4 kinase activity may lead to moderate anti-inflammatory efficacy owing to the dual role of IRAK4 as an active kinase and a scaffolding protein. Herein, we report the design, synthesis, and biological evaluation of an efficient and selective IRAK4 proteolysis-targeting chimeric molecule that eliminates IRAK4 scaffolding functions. The most potent compound, LC-MI-3, effectively degraded cellular IRAK4, with a half-maximal degradation concentration of 47.3 nM. LC-MI-3 effectively inhibited the activation of downstream nuclear factor-κB signaling and exerted more potent pharmacological effects than traditional kinase inhibitors. Furthermore, LC-MI-3 exerted significant therapeutic effects in lipopolysaccharide- and Escherichia coli-induced acute and chronic inflammatory skin models compared with kinase inhibitors in vivo. Therefore, LC-MI-3 is a candidate IRAK4 degrader in alternative targeting strategies and advanced drug development.

Research progress of industrial wastewater treatment technology based on solar interfacial adsorption coupled evaporation process.

Solar interface evaporation is an effective method for the treatment of water that has low energy consumption. Adsorption is recognized to be one of the most stable wastewater treatment methods and is widely used. Combining solar interface evaporation with adsorption provides a novel and low-cost approach for the efficient removal of heavy metals and organic pollutants from industrial wastewater. This paper reviews the characteristics and application of some common wastewater treatment methods. The photothermal conversion and the conceptual design of interface evaporation combined with adsorption are introduced and the photo-thermal conversion and adsorption methods are discussed. The study provides a summary of recent studies and advancements in interfacial evaporation-coupled adsorption materials, which include hydrogels, aerogels, and biomass materials for adsorption, and carbon materials for photothermal conversion. Finally, the current challenges encountered in industrial wastewater treatment are outlined and its prospects are discussed. The aim of this review is to explore a wide range of possibilities with the interfacial evaporation-coupled adsorption method and propose a new low-cost and high-efficiency method for industrial wastewater treatment.

Global richness patterns of alpine genus Gentiana depend on multiple factors.

Environmental factors impact species richness differently across taxonomic groups, and understanding the geographic patterns and drivers influencing alpine plant richness remains limited. This study compiled global distribution data of 404 species of Gentiana, an alpine genus, and analyzed the relative effects of different environmental factors and several previously proposed models on the variation of Gentiana richness. By evaluating the effects of range size and regions on the relationships between Gentiana richness and environmental factors, we found that all tested environmental factors had weak effects on richness variation for all species and wide-ranging species, while habitat heterogeneity was the best predictor for narrow-ranging species. Habitat heterogeneity was the main driver of richness variation in Europe and Asia, but not in North America. The multiple regression model that included variables for energy, water, seasonality, habitat heterogeneity and past climate change had the highest explanatory power, but it still explained less than 50% of the variation in species richness for all Gentiana species at both global and regional scale, except for Europe. The limited explanatory power of environmental factors in explaining species richness patterns for all species, along with the variations observed among regions, suggest that other factors, such as evolutionary processes and biogeographic history may have also influenced the geographic patterns of Gentiana species richness. In conclusion, our results indicate a limited influence of climate factors on alpine species richness, while habitat heterogeneity, along with its impacts on speciation and dispersal, likely play significant roles in shaping the richness of alpine Gentiana species.

Collision Oxidation Behavior of Silver Nanoparticles in Alkaline Solution.

In recent years, silver nanoparticles (Ag NPs) have been used as positive electrode material for zinc/silver batteries, and the silver oxides formed during the charging process determine the discharge performance of batteries. Therefore, it is important to study the oxidation behavior of Ag NPs in alkaline solution. Single-nanoparticle collision is an important tool for analyzing oxidation behavior of individual nanoparticles. Based on thermodynamic information from collision events, it is known that oxidation products are potential-dependent and size-dependent. Based on dynamic information, including collisional peak shapes and duration time, it was observed that the Ag NP collision oxidation process changed from stepwise oxidation to direct oxidation as the potential increased or size decreased. This work provides guidance for application of Ag NPs in zinc/silver batteries and proposed a strategy for oxidation behavior of individual NP that could be tracked in situ through an all-encompassing view of thermodynamic and dynamic information.

Effects of epidural analgesia on intrapartum maternal fever and maternal outcomes: an updated systematic review and meta-analysis.

OBJECTIVE: Epidural-related maternal fever in women is a common clinical phenomenon that leads to adverse consequences for mothers and neonates. The meta-analysis aimed to quantify the risk for intrapartum maternal fever after epidural analgesia (EA) stratified according to parity. The secondary objective was to investigate the association between EA and maternal outcomes. METHODS: An electronic literature search of the Medline/PubMed, Embase, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure databases was performed to identify studies reporting the occurrence of intrapartum fever in parturients. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and meta-analysis was performed using Review Manager version 5.3. RESULTS: Seventeen randomized controlled trials (RCTs) (5959 parturients) were included. Odds ratios for maternal fever in the analysis were 4.17 (95% confidence interval (CI) 2.93-5.94) and 5.83 (95% CI 4.96-6.87), respectively. Results of subgroup analysis according to parity were consistent. EA significantly prolonged the length of the first stage of labor (MD 34.52 [95% CI 12.13-56.91]) and the second stage of labor (MD 9.10 [95% CI 4.51-13.68]). Parturients who received EA were more likely to undergo instrumental delivery (OR 2.03 [95% CI 1.44-2.86]) and oxytocin augmentation (OR 1.45 [95% CI 1.12-1.88]). There were no differences in cesarean delivery rates between the EA and non-EA groups. CONCLUSIONS: Parturients who received EA exhibited a higher incidence of intrapartum fever. Credibility of the subgroup analyses was low because the mixed group did not effectively represent multiparas.

Psychological stressors involved in the pathogenesis of premature ovarian insufficiency and potential intervention measures.

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.

The role of transcription factors in the pathogenesis and therapeutic targeting of vascular diseases.

Transcription factors (TFs) constitute an essential component of epigenetic regulation. They contribute to the progression of vascular diseases by regulating epigenetic gene expression in several vascular diseases. Recently, numerous regulatory mechanisms related to vascular pathology, ranging from general TFs that are continuously activated to histiocyte-specific TFs that are activated under specific circumstances, have been studied. TFs participate in the progression of vascular-related diseases by epigenetically regulating vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). The Krüppel-like family (KLF) TF family is widely recognized as the foremost regulator of vascular diseases. KLF11 prevents aneurysm progression by inhibiting the apoptosis of VSMCs and enhancing their contractile function. The presence of KLF4, another crucial member, suppresses the progression of atherosclerosis (AS) and pulmonary hypertension by attenuating the formation of VSMCs-derived foam cells, ameliorating endothelial dysfunction, and inducing vasodilatory effects. However, the mechanism underlying the regulation of the progression of vascular-related diseases by TFs has remained elusive. The present study categorized the TFs involved in vascular diseases and their regulatory mechanisms to shed light on the potential pathogenesis of vascular diseases, and provide novel insights into their diagnosis and treatment.

The effect of magnesium sulfate on emergence agitation in surgical adult patients undergoing general anesthesia: A systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: Investigating the effect of magnesium sulfate (MS) on emergence agitation (EA) in adult surgical patients following general anesthesia (GA). DESIGN: Systematic literature review and meta-analysis (PROSPERO number: CRD42023461988). SETTING: Review of published literature. PATIENTS: Adults undergoing GA. INTERVENTIONS: Intravenous administration of MS. MEASUREMENTS: We searched PubMed/MEDLINE, EMBASE, the Cochrane Library, Scopus, and Web of Science for publications until September 14, 2023. The primary outcome was the incidence of EA, while the secondary outcomes included the impact of MS on postoperative agitation score (PAS), emergence variables and adverse events. Relative risk (RR) with 95% confidence interval (CI) measured dichotomous outcome, while standardized mean difference (SMD) or mean difference (MD) with 95% CI measured continuous outcomes. MAIN RESULTS: Meta-analysis of five randomized controlled trials (RCTs) indicated that MS was associated with a lower incidence of EA at various time points (0 min: RR = 0.62, 95% CI [0.41, 0.95]; p = 0.183, I2 = 43.6%; 5 min: RR = 0.29, 95% CI [0.16, 0.52]; p = 0.211, I2 = 36%; 10 min: RR = 0.14, 95% CI [0.06, 0.32]; p = 0.449, I2 = 0%; 15 min: RR = 0.11, 95% CI [0.02, 0.55]; p = 0.265, I2 = 19.5%; 30 min: RR = 0.05, 95% CI [0.00, 0.91]; the postoperative period: RR = 0.21, 95% CI [0.09, 0.49]; p = 0.724, I2 = 0%;). Additionally, MS was associated with a reduced PAS at various time points except for 0 min. However, no significant differences were observed in extubation time, the length of stay in the post-anesthesia care unit, postoperative nausea and vomiting or total complications. CONCLUSIONS: Limited available evidence suggests that MS was associated with a lower incidence of EA. Nevertheless, further high-quality studies are warranted to strengthen and validate the effect of MS in preventing EA in adult surgical patients.

The Efficacy of Dietary Intake, Supplementation, and Blood Concentrations of Carotenoids in Cancer Prevention: Insights from an Umbrella Meta-Analysis.

Previous meta-analyses of multiple studies have suggested that dietary intake and blood concentrations of carotenoids, as well as dietary supplement of certain carotenoids, play a role in reducing the risk of cancer. However, the conclusions of these studies have been subject to controversy. We conducted an umbrella review of meta-analyses to comprehensively analyze and evaluate the evidence pertaining the association between carotenoids and cancer outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases of meta-analyses and systematic reviews up to June 2023. Our selection criteria encompassed meta-analyses of cohort and case-control studies, as well as randomized controlled clinical trials, which investigated the associations between carotenoids and cancer risk. We also determined the levels of evidence for these associations with AMSTAR 2 criteria. We included 51 eligible articles, including 198 meta-analyses for qualitative synthesis in the umbrella review. Despite the presence of moderate to high heterogeneity among the studies, dietary intake, supplementation, and blood concentrations of carotenoids were inversely associated with the risk of total cancer, and certain specific cancers of lung, digestive system, prostate, breast, head and neck, and others. Subgroup analysis also showed that individual carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, zeaxanthin, and lycopene) offer certain protection against specific types of cancers. However, high doses of carotenoid supplements, especially ß-carotene, significantly increased the risk of total cancer, lung cancer, and bladder cancer. Our umbrella meta-analysis supported that high intake of dietary carotenoids as a whole food approach could be more beneficial in reducing cancer risk. Concurrently, the findings suggest that the efficacy of single-carotenoid supplementation in cancer prevention remains a subject of controversy.