Establishing and Validating an Innovative Focal Adhesion-Linked Gene Signature for Enhanced Prognostic Assessment in Endometrial Cancer.

Studies have highlighted the significant role of focal adhesion signaling in cancer. Nevertheless, its specific involvement in the pathogenesis of endometrial cancer and its clinical significance remains uncertain. We analyzed TCGA-UCEC and GSE119041 datasets with corresponding clinical data to investigate focal adhesion-related gene expression and their clinical significance. A signature, "FA-riskScore," was developed using LASSO regression in the TCGA cohort and validated in the GSE dataset. The FA-riskScore was compared with four existing models in terms of their prediction performance. We employed univariate and multivariate Cox regression analyses towards FA-riskScore to assess its independent prognostic value. A prognostic evaluation nomogram based on our model and clinical indexes was established subsequently. Biological and immune differences between high- and low-risk groups were explored through functional enrichment, PPI network analysis, mutation mining, TME evaluation, and single-cell analysis. Sensitivity tests on commonly targeted drugs were performed on both groups, and Connectivity MAP identified potentially effective molecules for high-risk patients. qRT-PCR validated the expressions of FA-riskScore genes. FA-riskScore, based on FN1, RELN, PARVG, and PTEN, indicated a poorer prognosis for high-risk patients. Compared with published models, FA-riskScore achieved better and more stable performance. High-risk groups exhibited a more challenging TME and suppressive immune status. qRT-PCR showed differential expression in FN1, RELN, and PTEN. Connectivity MAP analysis suggested that BU-239, potassium-canrenoate, and tubocurarine are effective for high-risk patients. This study introduces a novel prognostic model for endometrial cancer and offers insights into focal adhesion's role in cancer pathogenesis.

Synthesis of Bimetallic Palladium/Zinc Oxide Nanocomposites Using Crocus sativus and Its Anticancer Activity via the Induction of Apoptosis in Cervical Cancer.

Palladium (Pd) and zinc oxide (ZnO) (Pd/ZnO NPs) bimettalic nanocomposites still lag much too far behind other nanoparticles investigated for various biological uses in the area of cancer treatments. Chemically created nanoparticles agglomerate under physiological conditions, impeding their use in biomedical applications. In this study, a straightforward and environmentally friendly method for creating bimetallic nanoparticles (NPs) by combining palladium (Pd) and zinc oxide (ZnO) using Crocus sativus extract (CS-Pd/ZnO NCs) was reported; the bio-synthesize bimetallic palladium/zinc oxide nanocomposites and their antioxidant and anti-cancer properties were assessed. The developed Pd/ZnO NPs were characterized using different approaches, including UV-vis, DLS, FTIR, EDX, and SEM analyses. The present investigation shows how nanocomposites are made, their distinctive properties, antioxidant activity, anticancer mechanisms, and their potential therapeutic applications. DPPH and ABTS tests were used to investigate antioxidant activity. Further, the effects of CS-Pd/ZnO NCs on HeLa cells were assessed using the cell viability, ROS generation, MMP levels, and induced apoptosis. Apoptosis induction was measured using an Annexin V-fluorescein isothicyanate assay. Cell DNA was stained with propidium iodide to evaluate the impact upon this cell cycle. Time-dependent cell death was carried on by CS-Pd/ZnO NCs. The maximum inhibitory effect was 59 ± 3.2 when dosages of 4.5 µg/mL or higher were delivered after 24 h of treatment. Additionally, the CS-Pd/ZnO NCs caused HeLa cells to undergo apoptosis. Apoptotic HeLa cells were present in 35.64% of the treated cells at 4.5 µg/mL, and the cell cycle arrest at G0/G1 phase occurred concurrently. According to these findings, the CS-Pd/ZnO NCs may be a promising candidate for the creation of brand-new cervical cancer treatment.

Novel sulfate solid supported binary Ru-Ir oxides for superior electrocatalytic activity towards OER and CER.

Electrolysis for producing hydrogen powered by renewable electricity can be dramatically expanded by adapting different electrolytes (brine, seawater or pure water), which means the anode materials must stand up to complex electrolyte conditions. Here, a novel catalyst/support hybrid of binary Ru3.5Ir1Ox supported by barium strontium sulfate (BaSrSO4) was synthesized (RuIrOx/BSS) by exchanging the anion ligands of support. The as-synthesized RuIrOx/BSS exhibits compelling oxygen evolution (OER) and chlorine evolution (CER) performances, which affords to 10 mA cm-2 with only overpotential of 244 mV and 38 mV, respectively. The performed X-ray adsorption spectra clearly indicate the presence of an interface charge transfer effect, which results in the assignment of more electrons to the d orbitals of the Ru and Ir sites. The theoretical calculations demonstrated that the electronic structures of the catalytic active sites were modulated to give a lower overpotential, confirming the intrinsically high OER and CER catalytic activity.

Defective blue titanium oxide induces high valence of NiFe-(oxy)hydroxides over heterogeneous interfaces towards high OER catalytic activity.

Nickel-iron (oxy)hydroxides (NiFeOxHy) have been validated to speed up sluggish kinetics of the oxygen evolution reaction (OER) but still lack satisfactory substrates to support them. Here, non-stoichiometric blue titanium oxide (B-TiOx) was directly derived from Ti metal by alkaline anodization and used as a substrate for electrodeposition of amorphous NiFeOxHy (NiFe/B-TiOx). The performed X-ray absorption spectroscopy (XAS) and density functional theory (DFT) calculations evidenced that there is a charge transfer between B-TiOx and NiFeOxHy, which gives rise to an elevated valence at the Ni sites (average oxidation state ∼ 2.37). The synthesized NiFe/B-TiOx delivers a current density of 10 mA cm-2 and 100 mA cm-2 at an overpotential of 227 mV and 268 mV, respectively, which are better than that of pure Ti and stainless steel. It also shows outstanding activity and stability under industrial conditions of 6 M KOH. The post-OER characterization studies revealed that the surface morphology and valence states have no significant change after 24 h of operation at 500 mA cm-2, and also can effectively inhibit the leaching of Fe. We illustrate that surface modification of Ti which has high corrosion resistance and mechanical strength, to generate strong interactions with NiFeOxHy is a simple and effective strategy to improve the OER activity and stability of non-precious metal electrodes.

Gender-specific associations between abdominal adipose mass and bone mineral density in the middle-aged US population.

OBJECTIVES: The relationship between abdominal adipose tissue and osteoporosis is poorly understood. The purpose of this study was to examine the associations of abdominal adipose tissue with bone mineral density (BMD) among a nationally representative sample of US middle-aged adults. MATERIAL AND METHODS: This study included 1498 participants from the National Health and Nutrition Examination Survey 2013-2014 and 2017-2018. Dual-energy x-ray absorptiometry was used to measure BMD at the lumbar spine and femoral neck, as well as to assess abdominal adipose mass by categorizing total adipose tissue (TAT) into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Linear regression was used to assess the relationship between abdominal adipose tissue and BMD, and logistic regression and generalized additive model were used to assess the associations of abdominal adipose tissue with the development of low BMD. RESULTS: In our study, men accounted for 51.3%, and the mean age and body mass index for men and women were 49.3 and 49.6 years, and 23.9 and 28.3 kg/m2, respectively. In the univariate model, we found that abdominal adipose mass was positively associated with BMD at femoral neck and spine in both genders. In the multivariate model, among men, a negative correlation was observed between TAT and SAT and BMD at the femoral neck. Additionally, higher masses of TAT, SAT, and VAT were found to significantly increase the risk of low BMD at both the femoral neck and lumbar spine. In contrast, there was no significant association between abdominal adipose mass and BMD in middle-aged women, regardless of menopausal status. CONCLUSIONS: Our finding suggested that abdominal adipose tissue, regardless of its location (SAT or VAT), may have a negative impact on BMD in middle-aged men independently of body weight, but this relationship was not observed in women. Further research is needed to confirm these findings and investigate potential mechanisms underlying these associations.

Ultra-stable cryogenic sapphire cavity laser with an instability reaching 2 × 10-16 based on a low vibration level cryostat.

Cryogenic ultra-stable lasers have extremely low thermal noise limits and frequency drifts, but they are more seriously affected by vibration noise from cryostats. Main material candidates for cryogenic ultra-stable cavities include silicon and sapphire. Although sapphire has many excellent properties at low temperature, the development of sapphire-based cavities is less advanced than that of silicon-based. Using a homemade cryogenic sapphire cavity, we develop an ultra-stable laser source with a frequency instability of 2(1) × 10-16. This is the best frequency instability level among similar systems using cryogenic sapphire cavities reported so far. Low vibration performance of the cryostat is demonstrated with a two-stage vibration isolation, and the vibration suppression is optimized by tuning the mixing ratio of the gas-liquid-helium. With this technique, the linear power spectral densities of vibrations at certain frequencies higher than tens of hertz are suppressed by two orders of magnitude in all directions.

Intrinsic relationship between viscosity, viscosity index, and molecular structure of isoalkanes.

CONTEXT: Viscosity and viscosity index are the crucial properties of lubricant base stocks. Molecular dynamics simulation and quantum calculation were used to simulate the five isomers of C26H54 to study the intrinsic relationship between viscosity, viscosity index, and the molecular structure of isoalkanes. The results showed that the intermolecular interaction energy and the volume of rigid-like groups were the intrinsic factors that affected the viscosity and which could describe the viscosity quantitatively. The molecule conformation was studied by calculating the rotational energy barrier of the dihedral angle in the isoalkane molecule, and combined with molecular dynamics, the effect of temperature on the molecular conformation at 313 K and 373 K was further investigated. The α, ß, and γ carbon atoms adjacent to the tertiary carbon in the isoalkane molecule were difficult to rotate due to steric hindrance and could be regarded as rigid-like groups at 313 K. The tertiary carbon and the three adjacent carbon atoms formed a regular tetrahedral rigid-like group at 373 K. The changes in the intermolecular interaction energy and the volume of the rigid-like group with temperatures could better describe the viscosity index and reveal the fundamental reasons that affect the viscosity and the viscosity index. The molecular-level understanding of the relationship between the molecular structure and properties of isoalkanes provided theoretical support and scientific guidance for designing isoalkane molecules with specific properties. METHODS: Molecular dynamics simulation and quantum calculation were performed using Material Studio 8.0 software. The Amorphous Cell module was used to create an amorphous cell. The Foricite module was used for molecular dynamics simulation; the forcefield was assigned as COMPASS II. Nose-Hoover thermostat and Berendsen barostat were applied to maintain the temperature and pressure, respectively. To describe the non-bond interactions, the Ewald method was applied to calculate the van der Waals and electrostatic interactions. The Conformers module was used to study the conformation and the Dmol3 module was used to calculate the conformational energy with fine quality; the functional of GGA-PW91 and the basis set of DNP were used to calculate the energy.

Volatile Versus Total Intravenous Anesthesia on Postoperative Delirium in Adult Patients Undergoing Cardiac Valve Surgery: A Randomized Clinical Trial.

BACKGROUND: The effect of anesthesia regimens on postoperative delirium after on-pump cardiac valve surgery is yet undetermined. This study aimed to evaluate the effect of volatile anesthesia compared with propofol-based total intravenous anesthesia (TIVA) on the occurrence of delirium after on-pump cardiac valve surgery. METHODS: This randomized clinical trial was conducted at a university academic hospital in China, from February 2019 to January 2021. Patients scheduled for on-pump cardiac valve surgery or combined valve with coronary artery bypass grafting (CABG) surgeries were randomly assigned to receive anesthesia maintenance with either a volatile anesthetic (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was the incidence of delirium during the first 7 days after surgery, assessed using the confusion assessment method for the intensive care unit (ICU). The secondary outcomes included duration of delirium, subtypes of delirium, 30-day mortality, pain score, major morbidity (including cerebral infarction, respiratory failure, and pneumonia), duration of mechanical ventilation, and lengths of ICU and hospital stay. The statistical analysis of the primary outcome variable was by Pearson's χ 2 test. RESULTS: Among the 684 patients analyzed (mean age, 53.8 years; 381 [55.7%] women), 676 were assessed for the primary outcome. Postoperative delirium occurred in 63 of 337 (18.7%) patients receiving volatile anesthesia versus 76 of 339 (22.4%) patients receiving propofol-based TIVA (relative risk, 0.80; 95% confidence interval [CI], 0.55-1.16; P = .231). There were no significant differences between the groups in any of the secondary outcomes. CONCLUSIONS: Among patients undergoing on-pump cardiac valve surgery, anesthesia maintenance with a volatile agent did not result in significantly fewer occurrences of postoperative delirium than propofol-based TIVA.

Effect of Volatile Anesthesia Versus Total Intravenous Anesthesia on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.

OBJECTIVES: The purpose of this study was to evaluate the effect of volatile anesthesia and propofol-based total intravenous anesthesia (TIVA) on postoperative pulmonary complications (PPCs) among patients undergoing cardiac surgery. DESIGN: Parallel-group, randomized controlled trial. SETTING: Single-center tertiary care hospital. PARTICIPANTS: Five hundred twenty-four patients undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: The patients were assigned randomly (1:1) to receive anesthesia maintenance with a volatile anesthetic (sevoflurane or desflurane) or propofol-based TIVA. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of postoperative pulmonary complications within the first 7 postoperative days. The PPCs occurred in 118 of 262 patients (45.0%) in the volatile anesthesia group compared with 105 of 262 patients (40.1%) in the propofol-based intravenous anesthesia group (relative risk: 1.17 [95% CI 0.96-1.42], p = 0.123). There were no significant differences in the severity of PPCs within 7 days postoperatively, the occurrence and severity grade of PPCs within 30 days, the incidence of hypoxia, and 30-day mortality. CONCLUSIONS: In adult patients undergoing cardiac surgery with cardiopulmonary bypass, general anesthesia with a volatile anesthetic compared with propofol-based TIVA had not reduced pulmonary complications within the first 7 days after surgery.

Preparation and Characterization of Calcium-Incorporated Rosa roxburghii Tratt and Its Efficacy on Bone Mineral Density in Rats.

The deficiency of traditional calcium preparation will gradually be replaced by the new type of calcium preparation. Rosa roxburghii fruit (R. roxburghii) is popular for its rich nutrients and functional ingredients. The fermentation broth of R. roxburghii, involving amino acids, flavonoids, triterpenes, polysaccharides, and other compounds, is favorable for calcium chelation. Thus, this study fabricated calcium-incorporated R. roxburghii (FECa) and further illustrated its efficacy on bone mineral density (BMD) in rats. The calcium holding capacity of FECa was identified and confirmed using AAS. Ion complexation of FECa was characterized using 1H-NMR, UV, SEM and EDS, and FTIR. The calcium contents of femurs were increased by 36%, and the bone trabeculae of femurs were significantly increased. Net calcium balance was enhanced to further improve BMD by oral administration of FECa. The above results indicate that FECa can be a potential and efficient calcium supplementation agent.

Evaluation of the effects of Ipomoea staphylina on ovarian cancer cell line.

Ovarine cancer is a common woman malignancy in the world. Majority of the ovarian cancers are originated in the epithelial region which are lack of symptomps and this type of cancer is often get localized, when the tumour has spread outside the pelvis. Based on this context, the present study evaluated the effects of both aqueous and ethanolic extracts of Ipomoea staphylina leaves on ovarian cancer cell line. The SKOV-3 ovarian cancer cell line was used for evaluation of the effects of both extracts. Both extracts showed IC50 effects on ovarian cancer cell lines as sensitivity index (SI) for both extracts were recorded to above 1.iFurther, ethanol extract was more effective in the moderation of gene expressions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in comparison to aqueous extract. Further, morphological changes of SKOV-3 cells after treatment with both extracts also confirmed the results. The study, therefore, concludes that the ethanolic extract of Ipomoea staphylina leaves is more effective against ovarian cancer cell line.

Single step zero-thermal-expansion temperature measurement of optical reference cavities.

State-of-the-art laser frequency stability has been pushed to the 10-17 level. The laser reference cavity is typically nested in a multi-layer thermal enclosure to increase vacuum thermal time constant and thermally controlled at the zero-thermal-expansion temperature to reduce the external temperature fluctuation effect. It is rather time consuming to accurately determine the zero-thermal-expansion temperature for a large thermal time constant system. Here we develop a fast method for measuring the zero-thermal-expansion temperature of the cavity by relying on just one single temperature scan. We first develop a theoretical model to predict the performance of the laser locked to the reference cavity, and then construct an evaluation system for verification of the model. The zero-thermal-expansion temperature of a 30-cm cavity is measured to be 4.3±0.5 °C. The fast and high precision method for determining the zero-thermal-expansion temperature will be valuable in improving long-term frequency stabilities of cavity stabilized lasers.

UPLC-MS/MS-Based Rat Serum Metabolomics Reveals the Detoxification Mechanism of Psoraleae Fructus during Salt Processing.

Psoraleae Fructus (PF) is a botanical medicine widely used in Asian countries, of which salt products have higher safety and efficacy. However, the biological mechanism of the detoxification of salt-processing Psoraleae Fructus (SPF) has not yet been revealed. In this study, UPLC-MS/MS technology was used to explore the metabolic differences between SPF and PF in normal rats and reveal the mechanism of salt processing. The histopathological results of rat liver and kidney showed that the degree of liver and kidney injure in the SPF group was less than that in the PF group. The results of metabolomics showed that the detoxification mechanism of PF by salt processing might be related to glycerophospholipid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, arginine and proline metabolism, phenylalanine metabolism, and linoleic acid metabolism. PF-induced inflammation could be reduced by regulating the expression of metabolites to achieve the purpose of salt processing and detoxification. It included reducing the production of metabolites such as 1-acyl-sn-glycero-3-phosphocholine, sn-glycero-3-phosphocholine, tyrosine, arginine, linoleic acid, arachidonic acid, and phenylacetylglycine/hippuric acid ratio and upregulating the expression of metabolites such as creatine.

Vibration Property of a Cryogenic Optical Resonator within a Pulse-Tube Cryostat.

Cryogenic ultrastable laser cavities push laser stability to new levels due to their lower thermal noise limitation. Vibrational noise is one of the major obstacles to achieve a thermal-noise-limited cryogenic ultrastable laser system. Here, we carefully analyze the vibrational noise contribution to the laser frequency. We measure the vibrational noise from the top of the pulse-tube cryocooler down to the experiment space. Major differences emerge between room and cryogenic temperature operation. We cooled a homemade 6 cm sapphire optical resonator down to 3.4 K. Locking a 1064 nm laser to the resonator, we measure a frequency stability of 1.3×10-15. The vibration sensitivities change at different excitation frequencies. The vibrational noise analysis of the laser system paves the way for in situ accurate evaluation of vibrational noise for cryogenic systems. This may help in cryostat design and cryogenic precision measurements.

Hydroxyethyl starch 130/0.4 for volume replacement therapy in surgical patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The safety of perioperative intravenous hydroxyethyl starch (HES) products, specifically HES 130/0.4, continues to be the source of much debate. The aim of this meta-analysis was to update the existing evidence and gain further insight into the clinical effects of HES 130/0.4 on postoperative outcomes for volume replacement therapy in surgical patients. METHODS: MEDLINE, EMBASE, and Cochrane Library databases were searched from inception to March 2020 for relevant randomized controlled trials (RCTs) on perioperative use of HES 130/0.4 in adult surgical patients. The primary outcome was postoperative mortality and secondary outcomes were the incidence of acute kidney injury (AKI) and requirement for renal replacement therapy (RRT). The analysis was performed using the random-effects method and the risk ratio (RR) with a 95% confidence interval (CI). We performed the risk-of-bias assessment of eligible studies and assessed the overall quality of evidence for each outcome. RESULTS: Twenty-five RCTs with 4111 participants were finally included. There were no statistical differences between HES 130/0.4 and other fluids in mortality at 30 days (RR 1.28, 95% CI 0.88 to 1.86, p = 0.20), the incidence of AKI (RR 1.23, 95% CI 0.99 to 1.53, p = 0.07), or requirement for RRT (RR 0.75, 95% CI 0.37 to 1.53, p = 0.43). Overall, there was a moderate certainty of evidence for all the outcomes. There was no subgroup difference related to the type of surgery (p = 0.17) in the incidence of AKI. As for the type of comparator fluids, however, there was a trend that was not statistically significant (p = 0.06) towards the increased incidence of AKI in the HES 130/0.4 group (RR 1.22, 95% CI 0.97 to 1.54) compared with the crystalloid group (RR 1.21, 95% CI 0.27 to 3.91). Subgroup analyses according to the type of surgery demonstrated consistent findings. CONCLUSIONS: This systematic review and meta-analysis suggests that the use of HES 130/0.4 for volume replacement therapy compared with other fluids resulted in no significant difference in postoperative mortality or kidney dysfunction among surgical patients. Given the absent evidence of confirmed benefit and the potential trend of increased kidney injury, we cannot recommend the routine clinical use of HES 130/0.4 for volume replacement therapy in surgical patients from the perspective of benefit/risk profile. However, the results need to be interpreted with caution due to the limited sample size, and further well-powered RCTs are warranted. TRIAL REGISTRATION: PROSPERO registry reference: CRD42020173058.

Lycium barbarum polysaccharides inhibit ischemia/reperfusion-induced myocardial injury via the Nrf2 antioxidant pathway.

Oxidative stress is considered to be one of main pathophysiological mechanisms in myocardial ischemia/reperfusion (I/R) injury. Lycium barbarum polysaccharides (LBP), the main ingredient of Lycium barbarum, have potential antioxidant activity. We aimed to investigate the effects of LBP on myocardial I/R injury and explore the underlying mechanisms. Myocardial I/R group was treated with or without LBP to evaluate oxidative stress markers and the role of Nrf2 signal pathway. Our results showed that I/R increased infarct size and the activities of creatine kinase (CK) and lactate dehydrogenase (LDH) when compared with control group. Meanwhile, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were enhanced and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were decreased. These changes were associated with a significant increase in myocardial apoptosis, ultimately leading to cardiac dysfunction. LBP reduced infarct size (38.4 ± 2 % versus 19.4 ± 1.8 %, p < 0.05), CK and LDH activities and myocardial apoptotic index. Meanwhile, LBP suppressed the production of ROS and restored redox status. Additionally, LBP increased protein level of nuclear Nrf2 in vivo (2.1 ± 0.3 versus 3.8 ± 0.4, p < 0.05) and in vitro (1.9 ± 0.2 versus 3.8 ± 0.1, p < 0.05) and subsequently upregulated heme oxygenase 1 and NADPH dehydrogenase quinone 1 compared to I/R group. Interestingly, Nrf2 siRNA abolished the protective effects of LBP. LBP suppressed oxidative stress damage and attenuated cardiac dysfunction induced by I/R via activation of the Nrf2 antioxidant signal pathway.

The Effect of Propofol Versus Volatile Anesthetics on Persistent Pain After Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: Sternal incisions can generate persistent and intense post-sternotomy pain. Propofol has been shown to improve postoperative analgesia, but the preventive effect on persistent pain after cardiac surgery is unknown. The hypothesis of the present study was that intraoperative propofol-based anesthesia compared with volatile anesthesia could reduce the risk of chronic pain after cardiac surgery. DESIGN: A single-center, two-arm, patient-and-evaluator-blinded, randomized controlled trial. SETTING: A single major urban teaching and university hospital. PATIENTS: Five-hundred adult patients undergoing cardiac surgery via sternotomy randomly were assigned. With six withdrawals from the study and five from surgery, 244 in the total intravenous anesthesia group and 245 in the volatile group were included in the modified intention-to-treat analysis. INTERVENTIONS: Patients randomly were assigned to receive either propofol-based total intravenous anesthesia or volatile anesthesia during surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the incidence of pain at three, six, and 12 months after surgery defined as pain score >0 on the numeric rating scale. The secondary outcomes included acute pain, opioid use during the first 72 hours after surgery, and quality of life. The use of propofol did not significantly affect chronic pain at three months (55.4% v 52.9%, difference 2.5%, 95% confidence interval [CI] -6.6 to 11.6; p = 0.656), six months (35.5% v 37.5%, difference -2.0%, 95% CI -10.9 to 6.9; p = 0.657), or 12 months (18.2% v 20.7%, difference -2.5%, 95% CI -9.8 to 4.8; p = 0.495) compared with volatile anesthetics. Furthermore, there were no differences in acute pain score; morphine-equivalent consumption during the first 72 hours; and quality of life at three, six, and 12 months after surgery. CONCLUSIONS: Intraoperative administration of propofol did not reduce persistent pain after cardiac surgery compared with volatile anesthetics.

Comparison of low and high inspiratory oxygen fraction added to lung-protective ventilation on postoperative pulmonary complications after abdominal surgery: A randomized controlled trial.

STUDY OBJECTIVE: Intraoperative lung-protective ventilation strategy has been recommended to reduce postoperative pulmonary complications (PPCs). However, the role of inspiratory oxygen fraction (FiO2) in this protection remains highly uncertain. We aimed to evaluate the effect of intraoperative low (30%) versus high (80%) FiO2 in the context of lung-protective ventilation strategy on PPCs in patients undergoing abdominal surgery. DESIGN: Prospective, two-arm, randomized controlled trial. SETTING: Tertiary university hospital in China. PATIENTS: A total of ASA I-III 252 patients aged ≥18, who were scheduled for elective abdominal surgery under general anesthesia were included in the study. INTERVENTION: Patients were randomly assigned to receive either 30% or 80% FiO2 during the intraoperative period. All patients received volume-controlled mechanical ventilation with lung-protective ventilation approach, which included a tidal volume of 8 ml kg-1 of predicted body weight, a positive end-expiratory pressure level of 6-8 cmH2O, and repeated recruitment maneuvers. MEASUREMENTS: The primary outcome was a composite of postoperative pulmonary complications within the first 7 postoperative days, consisting of respiratory infection, respiratory failure, bronchospasm, atelectasis, pleural effusion, pneumothorax, and aspiration pneumonitis. The severity grade of PPCs was measured as a key secondary outcome. MAIN RESULTS: Two hundred and fifty-one patients completed the trial. PPCs occurred in 43 of 125 (34.4%) patients assigned to receive 30% FiO2 compared with 59 of 126 (46.8%) patients receiving 80% FiO2 (relative risk 0.74, 97.5% confidence interval, 0.51-1.02, p = 0.045, > 0.025). The severity of PPCs within the first 7 days following surgery was attenuated significantly in the low (30%) FiO2 group (p = 0.001). CONCLUSIONS: Among patients undergoing abdominal surgery under general anesthesia, an intraoperative lung-protective ventilation strategy with 30% FiO2 compared with 80% FiO2 did not reduce the incidence of PPCs. And the use of 30% FiO2 resulted in less severe pulmonary complications.

CPI-613 rewires lipid metabolism to enhance pancreatic cancer apoptosis via the AMPK-ACC signaling.

BACKGROUND: Pancreatic cancer remains one of the most rapidly progressive and deadly malignancies worldwide. Current treatment regimens only result in small improvements in overall survival for patients with this cancer type. CPI-613 (Devimistat), a novel lipoate analog inhibiting mitochondrial metabolism, shows the new hope for pancreatic cancer treatment as an efficient and well-tolerated therapeutic option treated alone or in combination with chemotherapy. METHODS: Pancreatic cancer cells growing in planar 2D cultures and 3D scaffold were used as research platforms. Cell viability was measured by MTT and alamarBlue, and apoptosis was assessed by JC-1 staining and flow cytometry with Annexin V-FITC/PI staining. The mechanism behind CPI-613 action was analyzed by western blot, transmission electron microscopy, and lipolysis assay kits, in the presence or absence of additional signaling pathway inhibitors or gene modifications. RESULTS: CPI-613 exhibits anticancer activity in pancreatic cancer cells by triggering ROS-associated apoptosis, which is accompanied by increased autophagy and repressed lipid metabolism through activating the AMPK signaling. Intriguingly, ACC, the key enzyme modulating lipid metabolism, is identified as a vital target of CPI-613, which is inactivated in an AMPK-dependent manner and influences apoptotic process upon CPI-613. Blockade or enhancement of autophagic process does not increase or blunt apoptosis to CPI-613, but inhibition of the AMPK-ACC signaling significantly attenuates apoptosis induced by CPI-613, suggesting CPI-613-mediated lipid metabolism reduction contributes to its cytotoxicity in pancreatic cancer cells. CONCLUSIONS: These findings explore the critical role of lipid metabolism in apoptosis, providing new insights into the AMPK-ACC signaling axis in crosstalk between lipid metabolism and apoptosis in CPI-613 treatment.

Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related deaths and calls for new druggable targets. We have previously highlighted the critical role of ADP-ribosylation factor-1 (Arf1) activation in HNSCC. In the present study, we address the question whether targeting Arf1 could be proposed as a valuable strategy against HNSCC. METHODS: We rationally designed and synthesized constrained ATC-based (4-amino-(methyl)-1,3-thiazole-5-carboxylic acid) γ-dipeptides to block Arf1 activation. We evaluated the effects of these γ-dipeptides in HNSCC cells: The cell viability was determined in 2D and 3D cell cultures after 72 h treatment and Arf1 protein levels and activity were assessed by GGA3 pull-down and Western blotting assays. RESULTS: Targeting Arf1 offers a valuable strategy to counter HNSCC. Our new Arf1-targeting compounds revealed a strong in vitro cytotoxicity against HNSCC cells, through inhibiting Arf1 activation and its downstream pathways. CONCLUSIONS: Arf1-targeting γ-dipeptides developed in this study may represent a promising targeted therapeutic to improve managing the HNSCC disease.