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Angewandte Chemie (International Ed. in... Jul 2024Photocatalytic synthesis of H2O2 is an advantageous and ecologically sustainable alternative to the conventional anthraquinone process. However, achieving high...
Photocatalytic synthesis of H2O2 is an advantageous and ecologically sustainable alternative to the conventional anthraquinone process. However, achieving high conversion efficiency without sacrificial agents remains a challenge. In this study, two covalent organic frameworks (COF-O and COF-C) were prepared with identical skeletal structures but with their pore walls anchored to different alkyl chains. They were used to investigate the effect of the chemical microenvironment of pores on photocatalytic H2O2 production. Experimental results reveal a change of hydrophilicity in COF-O, leading to suppressed charge recombination, diminished charge transfer resistance, and accelerated interfacial electron transfer. An apparent quantum yield as high as 10.3% (λ = 420 nm) can be achieved with H2O and O2 through oxygen reduction reaction. This is among the highest ever reported for polymer photocatalysts. This study may provide a novel avenue for optimizing photocatalytic activity and selectivity in H2O2 generation.
PubMed: 38953224
DOI: 10.1002/anie.202410179 -
Hospital Pediatrics Jul 2024Acute respiratory failure recalcitrant to conventional management often requires specialized organ-supportive technologies to optimize outcomes. Variation in the...
OBJECTIVE
Acute respiratory failure recalcitrant to conventional management often requires specialized organ-supportive technologies to optimize outcomes. Variation in the availability of these technologies prompted testing of the hypothesis that outcomes and resource use will vary by not only patient characteristics but also hospital characteristics and receipt of organ-supportive technology.
METHODS
Retrospective study of children 0 to 20 years old hospitalized for acute respiratory failure using the 2019 Kids' Inpatient Database. Multivariable regression models identified factors associated with mortality, length of hospitalization, and costs.
RESULTS
Of an estimated 75 365 hospitalizations nationally, 97% were to urban teaching hospitals, 57% were of children < 6 years, and 58% were of males. Complex chronic conditions (CCC) existed in 62%, multiorgan dysfunction in 35%, and extreme illness severity in 54%. Mortality was 7%, length of stay 15 days, and hospital costs $77 168. Elevated mortality was associated with cumulative organ dysfunction (odds ratio [OR]:2.31, 95% confidence interval [CI]: 2.22-2.42), CCC (OR: 5.49, 95% CI: 4.73-6.37), transfer, higher illness severity, and cardiopulmonary resuscitation. Lower mortality was associated with extracorporeal membrane oxygenation (OR: 0.36, 95% CI: 0.28-0.47) and new tracheostomy (OR: 0.30, 95% CI: 0.25-0.35). Longer hospitalization was associated with transfer, infancy, CCC, higher illness severity, cumulative organ dysfunction, and urban hospitals. Higher costs accrued with noninfants, cumulative organ dysfunction, private insurance, and urban teaching hospitals.
CONCLUSIONS
Hospitalizations for pediatric acute respiratory failure incurred substantial mortality and resource consumption. Efforts to reduce mortality and resource consumption should address interhospital transfer, access to organ-supportive technology, and drivers of higher severity-adjusted resource consumption at urban hospitals.
PubMed: 38953120
DOI: 10.1542/hpeds.2023-007166 -
Frontiers in Pharmacology 2024Diabetic retinopathy is a secondary microvascular complication of diabetes mellitus. This disease progresses from two stages, non-proliferative and proliferative...
Diabetic retinopathy is a secondary microvascular complication of diabetes mellitus. This disease progresses from two stages, non-proliferative and proliferative diabetic retinopathy, the latter characterized by retinal abnormal angiogenesis. Pharmacological management of retinal angiogenesis employs expensive and invasive intravitreal injections of biologic drugs (anti-vascular endothelial growth factor agents). To search small molecules able to act as anti-angiogenic agents, we focused our study on axitinib, which is a tyrosine kinase inhibitor and represents the second line treatment for renal cell carcinoma. Axitinib is an inhibitor of vascular endothelial growth factor receptors, and among the others tyrosine kinase inhibitors (sunitinib and sorafenib) is the most selective towards vascular endothelial growth factor receptors 1 and 2. Besides the well-known anti-angiogenic and immune-modulatory functions, we hereby explored the polypharmacological profile of axitinib, through a bioinformatic/molecular modeling approach and models of diabetic retinopathy. We showed the anti-angiogenic activity of axitinib in two different models of diabetic retinopathy, by challenging retinal endothelial cells with high glucose concentration (fluctuating and non-fluctuating). We found that axitinib, along with inhibition of vascular endothelial growth factor receptors 1 (1.82 ± 0.10; 0.54 ± 0.13, phosphorylated protein levels in fluctuating high glucose axitinib 1 µM, respectively) and vascular endothelial growth factor receptors 2 (2.38 ± 0.21; 0.98 ± 0.20, phosphorylated protein levels in fluctuating high glucose axitinib 1 µM, respectively), was able to significantly reduce ( < 0.05) the expression of Nrf2 (1.43 ± 0.04; 0.85 ± 0.01, protein levels in fluctuating high glucose axitinib 1 µM, respectively) in retinal endothelial cells exposed to high glucose, through predicted Keap1 interaction and activation of melanocortin receptor 1. Furthermore, axitinib treatment significantly ( < 0.05) decreased reactive oxygen species production (0.90 ± 0.10; 0.44 ± 0.06, fluorescence units in high glucose axitinib 1 µM, respectively) and inhibited ERK pathway (1.64 ± 0.09; 0.73 ± 0.06, phosphorylated protein levels in fluctuating high glucose axitinib 1 µM, respectively) in HRECs exposed to high glucose. The obtained results about the emerging polypharmacological profile support the hypothesis that axitinib could be a valid candidate to handle diabetic retinopathy, with ancillary mechanisms of action.
PubMed: 38953109
DOI: 10.3389/fphar.2024.1415846 -
Transplantation Direct Jul 2024Ex situ machine perfusion is increasingly used to preserve and assess donor livers before transplantation. Compared with traditional static cold storage (SCS), machine...
BACKGROUND
Ex situ machine perfusion is increasingly used to preserve and assess donor livers before transplantation. Compared with traditional static cold storage (SCS), machine perfusion exposes livers to an additional risk of microbial contamination. However, information on the risk of microbial transmission during machine perfusion is lacking.
METHODS
All livers that underwent either hypothermic oxygenated machine perfusion (HOPE) or normothermic machine perfusion (NMP) in our center between September 2021 and September 2023, and during which samples were taken from SCS fluid and/or machine perfusion solution for microbiological examination, were included in this retrospective, observational clinical study. Microbial transmission was examined from SCS fluid to machine perfusion solution fluid and, subsequently, to recipients of these livers.
RESULTS
A total of 90 cases of liver machine perfusion were included: 59 HOPE and 31 NMP. SCS preservation fluid cultures before HOPE or NMP were positive for at least 1 microorganism in 52% of the cases. After HOPE, there were no cases of positive machine perfusion fluid or evidence of microbial transmission to the recipients. After NMP, in 1 (3%) patient was grown from abdominal drain fluid, the same bacterial strain that was also grown from the SCS preservation fluid before NMP. This was resistant to the antibiotics that are routinely added to the NMP perfusion fluid.
CONCLUSIONS
The risk of microbial transmission after machine perfusion is very low but not absent. We recommend routine sampling of machine perfusion fluid at the end of the procedure for microbiological analysis.
PubMed: 38953041
DOI: 10.1097/TXD.0000000000001664 -
Research (Washington, D.C.) 2024Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor...
Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy.
PubMed: 38952997
DOI: 10.34133/research.0397 -
PeerJ 2024Andrographolide (Andro), an extract of (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and...
BACKGROUND
Andrographolide (Andro), an extract of (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear.
METHODS
The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy.
RESULTS
Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both and . The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro.
CONCLUSION
Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.
Topics: Reactive Oxygen Species; Diterpenes; Pancreatic Neoplasms; Autophagy; Protein Deglycase DJ-1; Animals; Humans; Mice; Cell Line, Tumor; Apoptosis; Xenograft Model Antitumor Assays; Mice, Nude
PubMed: 38952980
DOI: 10.7717/peerj.17619 -
PeerJ 2024Mitochondrial creatine kinase (MtCK) plays a pivotal role in cellular energy metabolism, exhibiting enhanced expression in various tumors, including colorectal cancer...
BACKGROUND
Mitochondrial creatine kinase (MtCK) plays a pivotal role in cellular energy metabolism, exhibiting enhanced expression in various tumors, including colorectal cancer (CRC). Creatine kinase mitochondrial 2 (CKMT2) is a subtype of MtCK; however, its clinical significance, biological functions, and underlying molecular mechanisms in CRC remain elusive.
METHODS
We employed immunohistochemical staining to discern the expression of CKMT2 in CRC and adjacent nontumor tissues of patients. The correlation between CKMT2 levels and clinical pathological factors was assessed. Additionally, we evaluated the association between CKMT2 and the prognosis of CRC patients using Kaplan-Meier survival curves and Cox regression analysis. Meanwhile, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of in different CRC cell lines. Finally, we explored the biological functions and potential molecular mechanisms of CKMT2 in CRC cells through various techniques, including qRT-PCR, cell culture, cell transfection, western blot, Transwell chamber assays, flow cytometry, and co-immunoprecipitation.
RESULTS
We found that CKMT2 was significantly overexpressed in CRC tissues compared with adjacent nontumor tissues. The expression of CKMT2 is correlated with pathological types, tumor size, distant metastasis, and survival in CRC patients. Importantly, CKMT2 emerged as an independent prognostic factor through Cox regression analysis. Experimental downregulation of expression in CRC cell lines inhibited the migration and promoted apoptosis of these cells. Furthermore, we identified a novel role for CKMT2 in promoting aerobic glycolysis in CRC cells through interaction with lactate dehydrogenase B (LDHB).
CONCLUSION
In this study, we found the elevated expression of CKMT2 in CRC, and it was a robust prognostic indicator in CRC patients. CKMT2 regulates glucose metabolism amplifying the Warburg effect through interaction with LDHB, which promotes the growth and progression of CRC. These insights unveil a novel regulatory mechanism by which CKMT2 influences CRC and provide promising targets for future CRC therapeutic interventions.
Topics: Humans; Colorectal Neoplasms; Warburg Effect, Oncologic; Male; Female; Cell Line, Tumor; Prognosis; Creatine Kinase, Mitochondrial Form; Disease Progression; L-Lactate Dehydrogenase; Middle Aged; Cell Proliferation; Apoptosis; Gene Expression Regulation, Neoplastic
PubMed: 38952967
DOI: 10.7717/peerj.17672 -
PeerJ 2024Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, their clinical application is hindered by their inherent...
BACKGROUND
Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, their clinical application is hindered by their inherent variability, which is influenced by various factors, such as the tissue source, culture conditions, and passage number.
METHODS
MSCs were sourced from clinically relevant tissues, including adipose tissue-derived MSCs (ADMSCs, = 2), chorionic villi-derived MSCs (CMMSCs, = 2), amniotic membrane-derived MSCs (AMMSCs, = 3), and umbilical cord-derived MSCs (UCMSCs, = 3). Passages included the umbilical cord at P0 (UCMSCP0, = 2), P3 (UCMSCP3, = 2), and P5 (UCMSCP5, = 2) as well as the umbilical cord at P5 cultured under low-oxygen conditions (UCMSCP5L, = 2).
RESULTS
We observed that MSCs from different tissue origins clustered into six distinct functional subpopulations, each with varying proportions. Notably, ADMSCs exhibited a higher proportion of subpopulations associated with vascular regeneration, suggesting that they are beneficial for applications in vascular regeneration. Additionally, CMMSCs had a high proportion of subpopulations associated with reproductive processes. UCMSCP5 and UCMSCP5L had higher proportions of subpopulations related to female reproductive function than those for earlier passages. Furthermore, UCMSCP5L, cultured under low-oxygen (hypoxic) conditions, had a high proportion of subpopulations associated with pro-angiogenic characteristics, with implications for optimizing vascular regeneration.
CONCLUSIONS
This study revealed variation in the distribution of MSC subpopulations among different tissue sources, passages, and culture conditions, including differences in functions related to vascular and reproductive system regeneration. These findings hold promise for personalized regenerative medicine and may lead to more effective clinical treatments across a spectrum of medical conditions.
Topics: Mesenchymal Stem Cells; Humans; Umbilical Cord; Female; Adipose Tissue; Cells, Cultured; Chorionic Villi; Amnion; Cell Differentiation
PubMed: 38952966
DOI: 10.7717/peerj.17616 -
Biology of Sport Jul 2024This study examined the acute effects of exercise testing on immunology markers, established blood-based biomarkers, and questionnaires in endurance athletes, with a...
This study examined the acute effects of exercise testing on immunology markers, established blood-based biomarkers, and questionnaires in endurance athletes, with a focus on biological sex differences. Twenty-four healthy endurance-trained participants (16 men, age: 29.2± 7.6 years, maximal oxygen uptake ( ): 59.4 ± 7.5 ml · min · kg; 8 women, age: 26.8 ± 6.1 years, : 52.9 ± 3.1 ml · min · kg) completed an incremental submaximal exercise test and a ramp test. The study employed exploratory bioinformatics analysis: mixed ANOVA, k-means clustering, and uniform manifold approximation and projection, to assess the effects of exhaustive exercise on biomarkers and questionnaires. Significant increases in biomarkers (lymphocytes, platelets, procalcitonin, hemoglobin, hematocrit, red blood cells, cell-free DNA (cfDNA)) and fatigue were observed post-exercise. Furthermore, differences pre- to post-exercise were observed in cytokines, cfDNA, and other blood biomarkers between male and female participants. Three distinct groups of athletes with differing proportions of females (Cluster 1: 100% female, Cluster 2: 85% male, Cluster 3: 37.5% female and 65.5% male) were identified with k-means clustering. Specific biomarkers (e.g., interleukin-2 (IL-2), IL-10, and IL-13, as well as cfDNA) served as primary markers for each cluster, potentially informing individualized exercise responses. In conclusion, our study identified exercise-sensitive biomarkers and provides valuable insights into the relationships between biological sex and biomarker responses.
PubMed: 38952916
DOI: 10.5114/biolsport.2024.132998 -
Biology of Sport Jul 2024This systematic review aims to provide a summary of the results from individual studies that specifically focused on overweight or obese populations, regardless of age... (Review)
Review
This systematic review aims to provide a summary of the results from individual studies that specifically focused on overweight or obese populations, regardless of age or sex. The goal is to determine the effects of structured recreational team sports interventions (TSG) on metabolic health, body composition and physical fitness parameters when compared to passive or active control groups. This study adhered to the PRISMA guidelines for reporting a systematic review. A thorough examination of relevant literature was conducted on November 06, 2023, using three prominent databases: PubMed, Scopus, and the Web of Science. Inclusion criteria considered overweight (e.g., BMI 25.0-29.9 kg/m) and obese (e.g., BMI > 30 kg/m) populations exposed to training interventions using recreational team sports, while the comparator group consisted of the same populations not exposed to exercise (passive controls) or exposed to alternative training methods. The primary outcomes of interest were metabolic health parameters (glucose, waist circumference, blood pressure, cholesterol, triglycerides), body composition (e.g., fat mass, lean mass), as well as physical fitness parameters (e.g., aerobic fitness, muscular fitness). Only studies with two- or multi-arm designs, whether randomized or not, were eligible for inclusion. The PEDro scale was used to assess the methodological bias of the included studies. Out of the initial 275 titles retrieved, we deemed ten eligible for our study. In terms of body composition, TSG demonstrated a significant decrease in body mass index across three studies (-2.3 to -5.1%) and a significant reduction in waist circumference in four studies (-4.6% to -8.4%). Regarding blood pressure, TSG exhibited a significant decrease in systolic blood pressure in two studies (-3.9% to -8.3%), while diastolic blood pressure showed a significant decrease in only one study (-7.3%). Cholesterol levels saw a significant decrease in TSG in three studies (-7.0% to -9.7%), and triglyceride levels showed a significant reduction in four studies (-16.4% to -20.1%). In terms of aerobic fitness, TSG demonstrated within-group improvements in the field-based tests in three studies (8.1% to 79.0%), and within-group improvements in maximal oxygen uptake in four studies (6.5% to 31.0%), with significant favoring of TSG in most studies. Overall, TSG demonstrated significant benefits for overweight and obese populations compared to the control group, particularly in terms of improvements in body mass index, systolic blood pressures, cholesterol and triglyceride levels, and aerobic fitness. Future research ought to concentrate on tailoring responses to varying training volumes on an individualized basis.
PubMed: 38952914
DOI: 10.5114/biolsport.2024.134762