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This review article provides overall understanding of stainless, environment-friendly, and nonflammable Mg alloys (SEN alloys) recently developed at the Korea Institute of Materials Science. SEN alloys are produced by adding small amounts of Ca and Y (each

Objective To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). Methods We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. Results In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). Conclusion Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.

Abstract Objective To investigate the differences in the niacin skin flushing response of adolescent depressed patients and healthy adolescents and its diagnostic value in adolescent depression. Methods Thirty-eight cases of acute episodes of depression in unmedicated adolescents and 47 age- and sex-matched healthy controls were included as study subjects, and sociodemographic and clinical data were collected, all of which were stimulated with six concentration gradients (up to 60 mmol/L, followed by sequential 3-fold gradient dilution to a minimum of 0.25 mmol/L) of niacin solution on the forearm skin, and the skin flushing area was applied as an assessment index. Results The total area of redness of the skin in response to niacin was significantly lower in the adolescent depression group than in the healthy adolescent group (Z=-3.36, p = 0.001) and was able to distinguish the adolescent depression group from the healthy adolescent group (area under curve = 0.713, sensitivity 51.1%, specificity 83.2%). Conclusions Niacin sensitivity is reduced in adolescent depressed patients, and the niacin skin flush response has potential clinical value as a diagnostic biomarker for adolescent depression.

Studies on somatic mutations in cloned animals have revealed slight genetic variances between clones and their originals, but have yet to identify the precise effects of these differences within the organism. Somatic mutations contribute to aging and are implicated in tumor development and other age-related diseases. Thus, we compared whole genome sequencing data from an original dog with that of cloned dogs, identifying candidate somatic mutations that were disproportionately located within genes previously implicated in aging. The substitutional signature of cloning-specific somatic mutations mirrored the uniform distribution characteristic of the signature associated with human aging. Further analysis of genes revealed significant enrichment of traits associated with body size as well as the molecular mechanisms underlying neuronal function and tumorigenesis. Overall, the somatic mutations found in cloned dogs may indicate a conserved mechanism driving aging across species and a broad spectrum of pathway alterations.

The influence of carbide precipitation on the mechanical properties of hot work tool steels was investigated in this study. Compared to the commercial H13 hot work tool steel, the KMoW and RW steels containing W exhibited a reduced high-temperature softening and an enhanced thermal fatigue resistance during long-term aging. These improvements can be attributed to the increased structural and chemical stability of V-rich MC carbides. The increased (W + Mo)/(V + Fe) atomic ratios at MC metallic sites increased their coherency as well as reduced the driving force required for the precipitation of Cr-rich carbides. These findings suggest that the addition of W effectively improves the heat-checking resistance and mechanical properties of hot work tool steels.

A medium carbon steel 34SiMn2CrNiMo was designed and fabricated, and the relationships between processing, microstructures and mechanical properties were established through microstructure characterization and mechanical properties testing on the quenching and partitioning(Q&P) heat-treated samples. Based on the experiment results of thermal expansion transformation behavior, the effects of quenching temperature TQ, heating approach, partitioning temperature TP and partitioning time tP on microstructures evolution were investigated and mechanism of strength and toughness was illuminated as well. The results show that multiphase microstructures of martensite and retained austenite can be obtained by means of Q&P processing, as a result the match of strength and plasticity is greatly improved. In the optimal treatment state, the retained austenite volume fraction is about 24%, the yield strength is 1053 MPa, the tensile strength is 1607 MPa, the elongation is 24.9%, and the product of strength and elongation(PSE) is 40.0 GPa·%. To avoid forming the blocky secondary martensite, the best quenching temperature has to be set at least 150 ℃ below martensitic transformation starting temperature Ms. More retained austenite can be achieved by slow heating than fast heating upon partitioning after the steel is incompletely quenched, the plasticity and toughness are improved apparently. The microstructures and properties of Q&P treated steel keep relatively stable with prolonged duration when it is partitioned at 400 ℃. However, the volume fraction of retained austenite decreases with tP at 450 ℃, leading the yield strength and elongation decrease simultaneously.

Objective: In order to solve the problem of poor stability, high cost and small gas flow of ternary gas mixing equipment. Methods: A ternary gas mixing system based on the ideal gas law and Dalton's law of partial pressure was proposed, and the system calculated errors and adjusted parameters by the designed algorithm, and adopted the connection of cylinder, sensor and so on. Results: After adjusting the mixing according to the relative deviation, the average relative deviation of the gas concentration of CO2 and O2 was 0.86% and 0.75% respectively, and the gas concentration accuracy met the technical requirements of ＜1%, and the high-precision gas mixing of the ternary gas can be better achieved. Conclusion: The system can realize rapid and stepless regulation of ternary gas, and high-precision continuous mixing.

The integration of artificial intelligence (AI) into drug discovery has markedly advanced the search for effective therapeutics. In our study, we employed a comprehensive computational–experimental approach to identify potential anti-SARS-CoV-2 compounds. We developed a predictive model to assess the activities of compounds based on their structural features. This model screened a library of approximately 700,000 compounds, culminating in the selection of the top 100 candidates for experimental validation. In vitro assays on human intestinal epithelial cells (Caco-2) revealed that 19 of these compounds exhibited inhibitory activity. Notably, eight compounds demonstrated dose-dependent activity in Vero cell lines, with half-maximal effective concentration (EC50) values ranging from 1 μM to 7 μM. Furthermore, we utilized a clustering approach to pinpoint potential nucleoside analog inhibitors, leading to the discovery of two promising candidates: azathioprine and its metabolite, thioinosinic acid. Both compounds showed in vitro activity against SARS-CoV-2, with thioinosinic acid also significantly reducing viral loads in mouse lungs. These findings underscore the utility of AI in accelerating drug discovery processes.

Age-related diseases represent the largest threat to public health. Aging is a degenerative, systemic, multifactorial and progressive process, coupled with progressive loss of function and eventually leading to high mortality rates. Excessive levels of both pro- and anti-oxidant species qualify as oxidative stress (OS) and result in damage to molecules and cells. OS plays a crucial role in the development of age-related diseases. In fact, damage due to oxidation depends strongly on the inherited or acquired defects of the redox-mediated enzymes. Molecular hydrogen (H2) has recently been reported to function as an anti-oxidant and anti-inflammatory agent for the treatment of several oxidative stress and aging-related diseases, including Alzheimer’s, Parkinson’s, cancer and osteoporosis. Additionally, H2 promotes healthy aging, increases the number of good germs in the intestine that produce more intestinal hydrogen and reduces oxidative stress through its anti-oxidant and anti-inflammatory activities. This review focuses on the therapeutic role of H2 in the treatment of neurological diseases. This review manuscript would be useful in knowing the role of H2 in the redox mechanisms for promoting healthful longevity.

The microstructures and mechanical properties of Mg–xBi (x = 2, 5, and 8 wt%) were investigated compared with pure Mg. The as-cast Mg–Bi billets consist of dendritic α-Mg grain matrix, divorced eutectic Mg3Bi2 phase and secondary precipitated Mg3Bi2 phase. After homogenization, secondary precipitated Mg3Bi2 particles were all dissolved into the matrix, while most of the divorced eutectic Mg3Bi2 intermetallic compounds retained. All the as-extruded samples exhibit fully dynamic recrystallization (DRX) and the average grain size decreases and the amount of nano-scale Mg3Bi2 precipitates increases with increasing Bi content. Additionally, Bi alloying has little influence on the texture of the as-extruded pure Mg, with all the samples showing typical basal texture. As the results of grain refinement and precipitation hardening, the strengths of the as-extruded samples increase under both tensile and compressive tests. Besides, the yield asymmetry significantly decreases with Bi content. Moreover, all the as-extruded samples represent similar ductility under compression, while the tensile elongation first increases and then decreases with more Bi added. The as-extruded Mg–5Bi alloy demonstrates good combination of strength and ductility. However, Mg–8Bi alloy displays lower tensile ductility than that of Mg–5Bi alloy due to the presence of abundant undissolved coarse Mg3Bi2 particles, which act as cracking sources during tensile test. Furthermore, the strain hardening rate Θ, strain hardening exponent n, and hardening capacity Hc are greatly reduced by Bi addition, mainly owing to the enhanced synergy effects of grain refinement and numerous Mg3Bi2 precipitates.

OBJECTIVES Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015. METHODS The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC). RESULTS The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids. CONCLUSIONS Consumption of opioids greatly increased in Korea over the 14-year study period.

Abstract Background Phase lag entropy (PLE) is a novel anesthetic depth indicator that uses four-channel electroencephalography (EEG) to measure the temporal pattern diversity in the phase relationship of frequency signals in the brain. The purpose of the study was to evaluate the anesthetic depth monitoring using PLE and to evaluate the correlation between PLE and bispectral index (BIS) values during propofol anesthesia. Methods In thirty-five adult patients undergoing elective surgery, anesthesia was induced with propofol using target-controlled infusion (the Schneider model). We recorded the PLE value, raw EEG, BIS value, and hemodynamic data when the target effect-site concentration (Ce) of propofol reached 2, 3, 4, 5, and 6 μg/ml before intubation and 6, 5, 4, 3, 2 μg/ml after intubation and injection of muscle relaxant. We analyzed whether PLE and raw EEG data from the PLE monitor reflected the anesthetic depth as the Ce of propofol changed, and whether PLE values were comparable to BIS values. Results PLE values were inversely correlated to changes in propofol Ce (propofol Ce from 0 to 6.0 μg/ml, r2 = − 0.83; propofol Ce from 6.0 to 2.0 μg/ml, r2 = − 0.46). In the spectral analysis of EEG acquired from the PLE monitor, the persistence spectrogram revealed a wide distribution of power at loss of consciousness (LOC) and recovery of consciousness (ROC), with a narrow distribution during unconsciousness. The power spectrogram showed the typical pattern seen in propofol anesthesia with slow alpha frequency band oscillation. The PLE value demonstrated a strong correlation with the BIS value during the change in propofol Ce from 0 to 6.0 μg/ml (r2 = 0.84). PLE and BIS values were similar at LOC (62.3 vs. 61.8) (P > 0.05), but PLE values were smaller than BIS values at ROC (64.4 vs 75.7) (P

Chlorambucil is a nitrogen mustard-based DNA alkylating drug, which is widely used as a front-line treatment of chronic lymphocytic leukaemia (CLL). Despite its widespread application and success for the initial treatment of leukaemia, a majority of patients eventually develop acquired resistance to chlorambucil. In this regard, we have designed and synthesised a novel hybrid molecule, chloram-HDi that simultaneously impairs DNA and HDAC enzymes. Chloram-HDi efficiently inhibits the proliferation of HL-60 and U937 leukaemia cells with GI50 values of 1.24 µM and 1.75 µM, whereas chlorambucil exhibits GI50 values of 21.1 µM and 37.7 µM against HL-60 and U937 leukaemia cells, respectively. The mechanism behind its remarkably enhanced cytotoxicity is that chloram-HDi not only causes a significant DNA damage of leukaemia cells but also downregulates DNA repair protein, Rad52, resulting in the escalation of its DNA-damaging effect. Furthermore, chloram-HDi inhibits HDAC enzymes to induce the acetylation of α-tubulin and histone H3.