Protective effects of fructose-1,6-bisphosphate postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing valve replacement: a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVES: Pharmacological postconditioning can protect against myocardial ischaemia-reperfusion injury during cardiac surgery with extracorporeal circulation. The aim of this study was to observe the protective effects of fructose-1,6-bisphosphate (FDP) postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing cardiac valve replacement with extracorporeal circulation. METHODS: Patients undergoing elective mitral valve replacement and/or aortic valve replacement were divided into normal saline postconditioning group (NS group) and FDP postconditioning group (FDP group). The primary outcome was the plasma concentration of creatine kinase-MB (CK-MB). The secondary outcomes were the plasma concentrations of lactate dehydrogenase, CK, high-sensitivity C-reactive protein, alpha-hydroxybutyrate dehydrogenase and cardiac troponin I, the spontaneous cardiac rhythm recovery profile, the extracorporeal circulation time and duration of surgery, intensive care unit and postoperative hospitalization. RESULTS: Forty patients were randomly assigned to receive intervention and included in the analysis. The serum concentrations of CK-MB, lactate dehydrogenase, CK, cardiac troponin I, alpha-hydroxybutyrate dehydrogenase and high-sensitivity C-reactive protein at T1∼4 were lower in the FDP group than in the NS group (P < 0.001). Compared with the NS group, the dosage of dopamine administered 1-90 min after cardiac resuscitation, the spontaneous cardiac rhythm recovery time and the incidence of ventricular fibrillation were lower in the FDP group (P < 0.001, P < 0.001 and P = 0.040, respectively). The values of ST- changes were increased more significantly in the NS group than in the FDP group (median [standard deviation] 1.3 [0.3] mm vs 0.7 [0.2] mm; P < 0.001). Compared with the NS group, the time of recovery of ST-segment deviations was shorter in the FDP group (50.3 [12.3] min vs 34.6 [6.9] min; P < 0.001). CONCLUSIONS: The FDP postconditioning could improve both myocardial ischaemia-reperfusion injury and the spontaneous cardiac rhythm recovery during cardiac valve surgery with extracorporeal circulation.

The median effective concentration of epidural ropivacaine with different doses of dexmedetomidine for motor blockade: an up-down sequential allocation study.

Study objective: Recent studies have shown that dexmedetomidine can be safely used in peripheral nerve blocks and spinal anesthesia. Epidural administration of dexmedetomidine produces analgesia and sedation, prolongs motor and sensory block time, extends postoperative analgesia, and reduces the need for rescue analgesia. This investigation seeks to identify the median effective concentration (EC50) of ropivacaine for epidural motor blockade, and assess how incorporating varying doses of dexmedetomidine impacts this EC50 value. Design: Prospective, double-blind, up-down sequential allocation study. Setting: Operating room, post-anesthesia care unit, and general ward. Interventions: One hundred and fifty patients were allocated into five groups in a randomized, double-blinded manner as follows: NR (normal saline combined with ropivacaine) group, RD0.25 (0.25 µg/kg dexmedetomidine combined with ropivacaine) group, RD0.5 (0.5 µg/kg dexmedetomidine combined with ropivacaine) group, RD0.75 (0.75 µg/kg dexmedetomidine combined with ropivacaine) group, RD1.0 (1.0 µg/kg dexmedetomidine combined with ropivacaine) group. The concentration of epidural ropivacaine for the first patient in each group was 0.5%. Following administration, the patients were immediately placed in a supine position for observation, and the lower limb motor block was assessed every 5 min using the modified Bromage score within 30 min after drug administration. According to the sequential method, the concentration of ropivacaine in the next patient was adjusted according to the reaction of the previous patient: effective motor block was defined as the modified Bromage score > 0 within 30 min after epidural administration. If the modified Bromage score of the previous patient was >0 within 30 min after drug administration, the concentration of ropivacaine in the next patient was decreased by 1 gradient. Conversely, if the score did not exceed 0, the concentration of ropivacaine in the next patient was increased by 1 gradient. The up-down sequential allocation method and probit regression were used to calculate the EC50 of epidural ropivacaine. Measurements: Adverse events, hemodynamic changes, demographic data and clinical characteristics. Main results: The EC50 of epidural ropivacaine required to achieve motor block was 0.677% (95% CI, 0.622-0.743%) in the NR group, 0.624% (95% CI, 0.550-0.728%) in the RD0.25 group, 0.549% (95% CI, 0.456-0.660%) in the RD0.5 group, 0.463% (95% CI, 0.408-0.527%) in the RD0.75 group, and 0.435% (95% CI, 0.390-0.447%) in the RD1.0 group. The EC50 of the NR group and the RD0.25 group were significantly higher than that of the RD0.75 and the RD1.0 groups, and the EC50 of the RD0.5 group was significantly higher than that of the RD1.0 group. Conclusion: The EC50 of epidural ropivacaine required to achieve motor block was 0.677% in the NR group, 0.624% in the RD0.25 group, 0.549% in the RD0.5 group, 0.463% in the RD0.75 group, and 0.435% in the RD1.0 group. Dexmedetomidine as an adjuvant for ropivacaine dose-dependently reduce the EC50 of epidural ropivacaine for motor block and shorten the onset time of epidural ropivacaine block. The optimal dose of dexmedetomidine combined with ropivacaine for epidural anesthesia was 0.5 µg/kg.

The optimal dose of dexmedetomidine as a 0.59% ropivacaine adjuvant for epidural anesthesia in great saphenous varicose vein surgery, based on hemodynamics and anesthesia efficacy: a randomized, controlled, double-blind clinical trial.

Objective: This study aimed to explore the optimal dose of dexmedetomidine as a 0.59% ropivacaine adjuvant for epidural anesthesia on perioperative hemodynamics and anesthesia efficacy in patients undergoing great saphenous varicose vein surgery. Methods: A total of 90 patients were randomly divided into three groups: 0.25 µg/kg dexmedetomidine combined with 0.59% ropivacaine epidural infusion group (ED1 group), 0.5 µg/kg dexmedetomidine combined with 0.59% ropivacaine epidural infusion group (ED2 group), and 0.75 µg/kg dexmedetomidine combined with 0.59% ropivacaine epidural infusion group (ED3 group). Hemodynamics, anesthesia efficiency, and adverse reactions were recorded. Main results: Compared with the ED1 group, the ED2 group had lower systolic blood pressure at T1-3 (T1, 95%CIs, 6.52-21.93, p < 0.001; T2, 95%CIs, 2.88-18.21, p = 0.004; T3, 95%CIs, 0.49-18.17, p = 0.035), and the diastolic blood pressure at T1-2 was decreased (T1, 95%CIs, 4.55-14.36, p < 0.001; T2, 95%CIs, 0.37-12.17, p = 0.033). Compared with the ED2 group, the ED3 group had higher systolic blood pressure at T1-2 (T1, 95%CIs, 5.90-21.46, p < 0.001; T2, 95%CIs, 2.07-17.55, p = 0.008) and higher diastolic blood pressure at T1-3 (T1, 95%CIs, 2.91-12.81, p = 0.001; T2, 95%CIs, 1.32-13.23, p = 0.011; T3, 95%CIs, 0.14-11.52, p = 0.043). Compared with the ED2 group, the heart rate was significantly decreased at T1-4 in the ED3 group (T1, 95%CIs, 2.25-15.72, p = 0.005; T2, 95%CIs, 2.35-13.82, p = 0.003; T3, 95%CIs, 0.50-9.79, p = 0.025; T4, 95%CIs, 1.46-10.36, p = 0.005). The myocardial oxygen consumption in all three groups was significantly decreased at each time point compared to T0 (p < 0.05 or < 0.001), and no significant between-group differences were detected (P>0.05). Compared with the ED1 group, the anesthesia efficiency of ED2 and ED3 groups was markedly enhanced, but the risk of bradycardia in ED2 and ED3 groups was dramatically increased (6 of 28 [21.4%] vs. 14 of 30 [46.7%] and 14 of 27 [51.9%], p = 0.023), one patient in the ED3 group experienced difficulty urinating, and remaining adverse reactions were mild in all three groups. Conclusion: A measure of 0.5 µg/kg dexmedetomidine is the optimal dose as a 0.59% ropivacaine adjuvant for epidural anesthesia in patients undergoing great saphenous varicose vein surgery. Clinical trial registration: http://www.chictr.org.cn/, registration number: ChiCTR2200060619.

[Applications of native mass spectrometry and ultraviolet photodissociation in protein structure and interaction analysis].

Dynamic changes in the structures and interactions of proteins are closely correlated with their biological functions. However, the precise detection and analysis of these molecules are challenging. Native mass spectrometry (nMS) introduces proteins or protein complexes into the gas phase by electrospray ionization, and then performs MS analysis under near-physiological conditions that preserve the folded state of proteins and their complexes in solution. nMS can provide information on stoichiometry, assembly, and dissociation constants by directly determining the relative molecular masses of protein complexes through high-resolution MS. It can also integrate various MS dissociation technologies, such as collision-induced dissociation (CID), surface-induced dissociation (SID), and ultraviolet photodissociation (UVPD), to analyze the conformational changes, binding interfaces, and active sites of protein complexes, thereby revealing the relationship between their interactions and biological functions. UVPD, especially 193 nm excimer laser UVPD, is a rapidly evolving MS dissociation method that can directly dissociate the covalent bonds of protein backbones with a single pulse. It can generate different types of fragment ions, while preserving noncovalent interactions such as hydrogen bonds within these ions, thereby enabling the MS analysis of protein structures with single-amino-acid-site resolution. This review outlines the applications and recent progress of nMS and UVPD in protein dynamic structure and interaction analyses. It covers the nMS techniques used to analyze protein-small-molecule ligand interactions, the structures of membrane proteins and their complexes, and protein-protein interactions. The discussion on UVPD includes the analysis of gas-phase protein structures and interactions, as well as alterations in protein dynamic structures, and interactions resulting from mutations and ligand binding. Finally, this review describes the future development prospects for protein analysis by nMS and new-generation advanced extreme UV light sources with higher brightness and shorter pulses.

The EC50 of propofol with different doses of dexmedetomidine during gastrointestinal endoscopy: A double-blind, placebo-controlled trial.

PURPOSE: The goal of this study was to evaluate the dose-response relationship between dexmedetomidine and propofol in sedating patients and to determine the optimal dosage of dexmedetomidine during gastrointestinal endoscopy. METHODS: One hundred fifty patients were divided into 5 groups, each receiving a loading dose of dexmedetomidine (0.4, 0.6, 0.8, 1.0 µg/kg) or saline, with propofol for sedation. The median effective concentration (EC50) of propofol was calculated using the modified Dixon up-and-down approach. Adverse effects, vital signs, procedure, and recovery times were recorded. RESULTS: The EC50 of propofol in groups NS, D0.4, D0.6, D0.8, and D1.0 were 3.02, 2.44, 1.97, 1.85, and 1.83 µg/mL, respectively. Heart rate in the dexmedetomidine groups decreased more than the NS group (P < .001). The mean arterial pressure (MAP) in the NS group experienced a decline compared to groups D0.8 and D1.0 when the plasma concentration and effect-site concentration reached equilibrium. Additionally, the respiratory rate was found to be lower in groups NS, D0.4, D0.6, and D0.8 (P < .05). Recovery time in groups D0.8 and D1.0 was longer than the NS group (P < .05). Bruggemann comfort scales score was higher in group D1.0 (P < .05). No significant difference was found in the incidences of hypotension and bradycardia, and the dose of ephedrine and atropine. Respiratory depression was significantly reduced in groups D0.8 and D1.0 compared to the NS group. CONCLUSION: A single dose of 0.6 to 0.8 µg/kg of dexmedetomidine should be recommended in combination with propofol for gastrointestinal endoscopy. And the EC50 of propofol is 1.97 to 1.85 µg/mL.

Panda-UV Unlocks Deeper Protein Characterization with Internal Fragments in Ultraviolet Photodissociation Mass Spectrometry.

Ultraviolet photodissociation (UVPD) mass spectrometry unlocks insights into the protein structure and sequence through fragmentation patterns. While N- and C-terminal fragments are traditionally relied upon, this work highlights the critical role of internal fragments in achieving near-complete sequencing of protein. Previous limitations of internal fragment utilization, owing to their abundance and potential for random matching, are addressed here with the development of Panda-UV, a novel software tool combining spectral calibration, and Pearson correlation coefficient scoring for confident fragment assignment. Panda-UV showcases its power through comprehensive benchmarks on three model proteins. The inclusion of internal fragments boosts identified fragment numbers by 26% and enhances average protein sequence coverage to a remarkable 93% for intact proteins, unlocking the hidden region of the largest protein carbonic anhydrase II in model proteins. Notably, an average of 65% of internal fragments can be identified in multiple replicates, demonstrating the high confidence of the fragments Panda-UV provided. Finally, the sequence coverages of mAb subunits can be increased up to 86% and the complementary determining regions (CDRs) are nearly completely sequenced in a single experiment. The source codes of Panda-UV are available at https://github.com/PHOENIXcenter/Panda-UV.

Assessment of the Conformation Stability and Glycosylation Heterogeneity of Lactoferrin by Native Mass Spectrometry.

Lactoferrin (LTF) has diverse biological activities and is widely used in functional foods and active additives. Nevertheless, evaluating the proteoform heterogeneity, conformational stability, and activity of LTF remains challenging during its production and storage processes. In this study, we describe the implementation of native mass spectrometry (nMS), glycoproteomics, and an antimicrobial activity assay to assess the quality of LTF. We systematically characterize the purity, glycosylation heterogeneity, conformation, and thermal stability of LTF samples from different sources and transient high-temperature treatments by using nMS and glycoproteomics. Meanwhile, the nMS peak intensity and antimicrobial activity of LTF samples after heat treatment decreased significantly, and the two values were positively correlated. The nMS results provide essential molecular insights into the conformational stability and glycosylation heterogeneity of different LTF samples. Our results underscore the great potential of nMS for LTF quality control and activity evaluation in industrial production.

Aqueous alkaline phosphate facilitates the non-exchangeable deuteration of peptides and proteins.

The incorporation of deuterium into peptides and proteins holds broad applications across various fields, such as drug development and structural characterization. Nevertheless, current methods for peptide/protein deuteration often target exchangeable labile sites or require harsh conditions for stable modification. In this study, we present a late-stage approach utilizing an alkaline phosphate solution to achieve deuteration of non-exchangeable backbone sites of peptides and proteins. The specific deuteration regions are identified through ultraviolet photodissociation (UVPD) and mass spectrometry analysis. This deuteration strategy demonstrates site and structure selectivity, with a notable affinity for labeling the α-helix regions of myoglobin. The deuterium method is particularly suitable for peptides and proteins that remain stable under high pH conditions.

Time-Resolved Ultraviolet Photodissociation Mass Spectrometry Probes the Mutation-Induced Alterations in Protein Stability and Unfolding Dynamics.

How mutations impact protein stability and structure dynamics is crucial for understanding the pathological process and rational drug design. Herein, we establish a time-resolved native mass spectrometry (TR-nMS) platform via a rapid-mixing capillary apparatus for monitoring the acid-initiated protein unfolding process. The molecular details in protein structure unfolding are further profiled by a 193 nm ultraviolet photodissociation (UVPD) analysis of the structure-informative photofragments. Compared with the wild-type dihydrofolate reductase (WT-DHFR), the M42T/H114R mutant (MT-DHFR) exhibits a significant stability decrease in TR-nMS characterization. UVPD comparisons of the unfolding intermediates and original DHFR forms indicate the special stabilization effect of cofactor NADPH on DHFR structure, and the M42T/H114R mutations lead to a significant decrease in NADPH-DHFR interactions, thus promoting the structure unfolding. Our study paves the way for probing the mutation-induced subtle changes in the stability and structure dynamics of drug targets.

Can green funds improve corporate environmental, social, and governance performance? Evidence from Chinese-listed companies.

Green funds play pivotal roles in driving corporate sustainable development. Utilizing data from Chinese publicly listed companies from 2010 to 2021, we examine the impact of green funds on corporate environmental, social, and governance (ESG) performance and the underlying mechanisms. The research findings claim that green funds positively affect corporate ESG performance. Mechanism analysis systematically demonstrates that green funds contribute to elevated corporate ESG performance by alleviating financial constraints, enhancing managerial efficiency, and fostering green innovation. Heterogeneity analysis further underscores that the effect of green funds is particularly potent in companies with high external attention. Furthermore, green funds also play significant roles in production capabilities and economic value. This research enriches the micro-level evidence on the development of green funds and furnishes substantial implications for sustainable development.

Ultrasound-guided caudal anaesthesia combined with epidural anaesthesia for caesarean section: a randomized controlled clinical trial.

BACKGROUND: Although epidural anaesthesia and spinal anaesthesia are currently the general choices for patients undergoing caesarean section, these two neuraxial anaesthesia methods still have drawbacks. Caudal anaesthesia has been considered to be more appropriate for gynaecological surgery. The purpose of this study was to compare epidural anaesthesia combined with caudal anaesthesia, spinal anaesthesia and single-space epidural anaesthesia for caesarean section with respect to postoperative comfort and intraoperative anaesthesia quality. METHODS: In this clinical trial, 150 patients undergoing elective caesarean section were recruited and randomized into three groups according to a ratio of 1:1:1to receive epidural anaesthesia only, spinal anaesthesia only or epidural anaesthesia combined with caudal anaesthesia. The primary outcome was postoperative comfort in the three groups. Secondary outcomes included intraoperative anaesthesia quality and the incidences of nausea, vomiting, postdural puncture headache, maternal bradycardia, or hypotension. RESULTS: More patients were satisfied with the intraoperative anaesthesia quality in the EAC group than in the EA group (P = 0.001). The obstetrician was more significantly satisfied with the intraoperative anaesthesia quality in the SA and EAC groups than in the EA group (P = 0.004 and 0.020, respectively). The parturients felt more comfortable after surgery in the EA and EAC groups (P = 0.007). The incidence of maternal hypotension during caesarean section was higher in the SA group than in the EA and EAC groups (P = 0.001 and 0.019, respectively). CONCLUSIONS: Epidural anaesthesia combined with caudal anaesthesia may be a better choice for elective caesarean section. Compared with epidural anaesthesia and spinal anaesthesia, it has a higher quality of postoperative comfort and intraoperative anaesthesia.

Probing the functional hotspots inside protein hydrophobic pockets by in situ photochemical trifluoromethylation and mass spectrometry.

Due to the complex high-order structures and interactions of proteins within an aqueous solution, a majority of chemical functionalizations happen on the hydrophilic sites of protein external surfaces which are naturally exposed to the solution. However, the hydrophobic pockets inside proteins are crucial for ligand binding and function as catalytic centers and transporting tunnels. Herein, we describe a reagent pre-organization and in situ photochemical trifluoromethylation strategy to profile the functional sites inside the hydrophobic pockets of native proteins. Unbiased mass spectrometry profiling was applied for the characterization of trifluoromethylated sites with high sensitivity. Native proteins including myoglobin, trypsin, haloalkane dehalogenase, and human serum albumin have been engaged in this mild photochemical process and substantial hydrophobic site-specific and structure-selective trifluoromethylation substitutes are obtained without significant interference to their bioactivity and structures. Sodium triflinate is the only reagent required to functionalize the unprotected proteins with wide pH-range tolerance and high biocompatibility. This "in-pocket" activation model provides a general strategy to modify the potential binding pockets and gain essential structural insights into the functional hotspots inside protein hydrophobic pockets.

Effects of dexmedetomidine combined with etomidate on postoperative cognitive function in older patients undergoing total intravenous anaesthesia: a randomized, double-blind, controlled trial.

BACKGROUND: Etomidate has been advocated for anesthesia in older and critically ill patients because of its hemodynamic stability. Clinical studies have shown that dexmedetomidine has neuroprotective and anti-inflammatory properties and improves postoperative cognitive dysfunction in older patients. The present study was to evaluate the effects of the combination of etomidate and dexmedetomidine with different anaesthesia time on postoperative cognitive function in older patients. METHODS: A total of 132 older patients undergoing ureteroscopic holmium laser lithotripsy were randomly divided into EN group and ED group equally. Patients whose surgery time was less than or equal to 1 h in each group were allocated to short-time surgery group (EN1 group and ED1 group), and whose surgery time was more than 1h were allocated to long-term surgery group (EN2 group and ED2 group). The primary outcome was the score of the Mini-Mental State Examination. The secondary outcomes were State-Trait Anxiety Inventory scores, Riker sedation agitation scores, Zung Self-Rating Depression Scale scores, the memory span for Arabic numerals, the plasma concentrations of S-100 calcium-binding protein B and neuron specific enolase, the time to spontaneous respiration, recovery, and extubation. RESULTS: The MMSE scores at t2-3 were higher in ED1 and ED2 groups than in EN1 and EN2 groups (p<0.05). Compared with ED1 and ED2 groups, the ZSDS scores, the S-AI scores and the T-AI scores at t1-2 were higher in EN1 and EN2 groups (p<0.05), respectively. The recalled Arabic numbers at t1-3 were higher in ED2 group than in EN2 group (p<0.05). The plasma concentration of S-100ß at t1-2 in EN1 group and t1-3 in EN2 group were higher than that in ED1 and ED2 groups (p<0.05), respectively. Compared with ED1 and ED2 groups, the plasma concentrations of NSE were higher at t1-3 in EN1 group and t1-4 in EN2 group (p<0.05), respectively. CONCLUSION: The administration of dexmedetomidine could improve postoperative cognitive dysfunction, emergence agitation, depression and anxiety, attenuate the plasma concentrations of S-100ß and NSE in older patients undergoing total intravenous anaesthesia with etomidate. TRIAL REGISTRATION: Registration number: ChiCTR1800015421, Date: 29/03/2018.

Copper neurotoxicity: Induction of cognitive dysfunction: A review.

Cognitive dysfunction occurs mainly in certain diseases and in the pathological process of aging. In addition to this, it is also widespread in patients undergoing anesthesia, surgery, and cancer chemotherapy. Neuroinflammation, oxidative stress, mitochondrial dysfunction, impaired synaptic plasticity, and lack of neurotrophic support are involved in copper-induced cognitive dysfunction. In addition, recent studies have found that copper mediates cuproptosis and adversely affects cognitive function. Cuproptosis is a copper-dependent, lipoylated mitochondrial protein-driven, non-apoptotic mode of regulated cell death, which provides us with new avenues for identifying and treating related diseases. However, the exact mechanism by which cuproptosis induces cognitive decline is still unclear, and this has attracted the interest of many researchers. In this paper, we analyzed the pathological mechanisms and therapeutic targets of copper-associated cognitive decline, mainly in the context of neurodegenerative diseases, psychiatric and psychological disorders, and diabetes mellitus.

Comparison of intravenous butorphanol vs. tramadol for post-spinal anesthesia shivering: a meta-analysis and systematic review.

Background: Patients often experience shivering after spinal anesthesia. In recent years, more and more studies have compared the efficacy and side effects of intravenous butorphanol and tramadol in the treatment of shivering after spinal anesthesia. Therefore, we conducted a MATE analysis and systematic review to compare the efficacy and side effects of butorphanol vs. tramadol in the treatment of shivering after spinal anesthesia. Methods: PubMed, Cochrane Library, and Embase databases were searched for randomized controlled trials (RCTs) from inception to 30 December 2022, comparing the effects of butorphanol vs. tramadol for the control of shivering after spinal anesthesia. Data assessment and collection were analyzed using the Review Manager 5.4 software. Results: Five randomized controlled trials involving 302 adult patients were included in this meta-analysis. The results showed that butorphanol has a shorter time to cease shivering (standardized mean difference (SMD) = -0.53; 95% confidence interval (CI) [-0.89, -0.17], P = 0.004, I2 = 0%), a higher rate of cessation of shivering within 1 min after administering the study drugs (relative risk (RR), 1.69; 95% CI [1.15,2.48], P = 0.008, I2 = 0%), and higher incidences of sedation (RR, 2.98; 95% CI [2.11, 4.21], P <0.00001, I2 = 0%), compared with tramadol. Conclusion: In the treatment of shivering after spinal anesthesia, butorphanol has a shorter onset time and a higher rate of cessation of shivering within 1 min after the study drugs were administered than tramadol. Therefore, butorphanol is superior to tramadol in the treatment of shivering after spinal anesthesia.

Corrigendum: 6-Shogaol inhibits oxidative stress-induced rat vascular smooth muscle cell apoptosis by regulating OXR1-p53 axis.

[This corrects the article DOI: 10.3389/fmolb.2022.808162.].

Molecular Structure Characterization of Micro/Nanoplastics by 193 nm Ultraviolet Photodissociation Mass Spectrometry.

The degradation of macroplastics results in micro/nanoplastics (MNPs) in the natural environment, inducing high health risks worldwide. It remains challenging to characterize the accurate molecular structures of MNPs. Herein, we integrate 193 nm ultraviolet photodissociation (UVPD) with mass spectrometry to interrogate the molecular structures of poly(ethylene glycol) terephthalate and polyamide (PA) MNPs. The backbones of the MNP polymer can be efficiently dissociated by UVPD, producing rich types of fragment ions. Compared to high-energy collision dissociation (HCD), the structural informative fragment ions and corresponding sequence coverages obtained by UVPD were all improved 2.3 times on average, resulting in almost complete sequence coverage and precise structural interrogation of MNPs. We successfully determine the backbone connectivity differences of MNP analogues PA6, PA66, and PA610 by improving the average sequence coverage from 26.8% by HCD to 89.4% by UVPD. Our results highlight the potential of UVPD in characterizing and discriminating backbone connectivity and chain end structures of different types of MNPs.

Effects of extracorporeal circulation with different time on platelet count after cardiac surgery: a retrospective study based on medical records.

Our objective was to observe the effects of extracorporeal circulation (ECC) with different time on platelet count in patients undergoing cardiac surgery. A total of 427 patients who underwent elective cardiac surgery under ECC in affiliated hospital of north Sichuan medical college from January 1, 2018 to July 31, 2021 were divided into three groups according to ECC time. We concluded that thrombocytopenia was common after ECC, maximum drop of the platelet counts after ECC was usually seen on the second day after ECC, and platelet counts started to recover on the fifth day after ECC. With the extension of ECC time, the drop in platelet counts is more pronounced, the volume of perioperative blood loss and blood products transfusion are more, and the recovery level and speed of platelet counts is lower.

Structural characterization of protein-material interfacial interactions using lysine reactivity profiling-mass spectrometry.

Understanding how proteins and materials interact is useful for evaluating the safety of biomedical micro/nanomaterials, toxicity estimation and design of nano-drugs and catalytic activity improvement of bio-inorganic functional hybrids. However, characterizing the interfacial molecular details of protein-micro/nanomaterial hybrids remains a great challenge. This protocol describes the lysine reactivity profiling-mass spectrometry strategy for determining which parts of a protein are interacting with the micro/nanomaterials. Lysine residues occur frequently on hydrophilic protein surfaces, and their reactivity is dependent on the accessibility of their amine groups. The accessibility of a lysine residue is lower when it is in contact with another object; allosteric effects resulting from this interaction might reduce or increase the reactivity of remote lysine residues. Lysine reactivity is therefore a useful indicator of protein localization orientation, interaction sequence regions, binding sites and modulated protein structures in the protein-material hybrids. We describe the optimized two-step isotope dimethyl labeling strategy for protein-material hybrids under their native and denaturing conditions in sequence. The comparative quantification results of lysine reactivity are only dependent on the native microenvironments of lysine local structures. We also highlight other critical steps including protein digestion, elution from materials, data processing and interfacial structure analysis. The two-step isotope labeling steps need ~5 h, and the whole protocol including digestion, liquid chromatography-tandem mass spectrometry, data processing and structure analysis needs ~3-5 d.

The potencies and neurotoxicity of intrathecal levobupivacaine in a rat spinal model: Effects of concentration.

This study was aimed at examining the anesthetic effects and spinal cord injuries in the rats by intrathecal injection of levobupivacaine at different concentrations. Rats with successful intrathecal cannulation were selected and randomly divided into six groups (n = 72), and administered 0.1 mL of 0.125%, 0.25%, 0.5%, or 0.75% levobupivacaine, saline or 5% lidocaine via intrathecal catheters. The potency of levobupivacaine was evaluated by walking behavior. To identify the motor and sensory function, walking behavior and paw withdrawal thresholds (PWTs) were measured once a day. After 7 days, the L4-5 spinal cord segments were removed for histological examination. The onset time of 0.125% levobupivacaine intrathecal injection was 70.0 ± 8.9 s, and the maintenance time was 9.5 ± 1.8 min. The onset time of 0.75% levobupivacaine intrathecal injection was significantly shortened to 31.0 ± 5.5 s, and the maintenance time was significantly extended to 31.3 ± 5.4 min. The severe injury was observed in the 5% lidocaine group, while milder injury was observed in the 0.75% levobupivacaine group. The damage in the 0.5% levobupivacaine group was mild, and there were no histological abnormalities in the 0.125%, 0.25% levobupivacaine and saline groups. The neurotoxicity of intrathecally administered levobupivacaine was concentration dependent. In addition, higher concentrations of levobupivacaine were associated with shorter onset and longer maintenance times. The clinical concentration of levobupivacaine should not exceed 0.5% to avoid potential damage.