Metabolic surgery can promote comprehensive physiological improvements to alleviate metabolic disorders, particularly for patients with type 2 diabetes. Nevertheless, the therapeutic scope has been limited owing to unexpectedly inconsistent surgical outcomes. Therefore, this study to overcome these obstacles by determining the fundamental mechanism underlying the conflicting outcomes. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified duodenal-jejunal bypass (DJB) procedures, were compared to understand the specific surgical patterns from different perspectives comprehensively. Patients in the nonobese group were exclusively included to prevent confounding effects from overweight patients with type 2 diabetes. Following intestinal anastomosis, the epithelial identity of the succeeding intestine was replaced by that of the proximal epithelium owing to altered crosstalk between the epithelium and opposing mesenchymal cells. Subsequent intestinal compensatory proliferation and rapid turnover rate accelerate the spread of the replaced epithelium. The main factors contributing to inconsistent outcomes of metabolic surgery are inadequate duodenal exclusion and inappropriate biliopancreatic limb length. Replacement of enteroendocrine cells during regeneration can lead to inconsistent outcomes in metabolic surgery. The type and density of enteroendocrine cells distributed at the terminal end of the proximal intestine play a significant role in diverse outcomes of metabolic surgery.

Metabolic surgery can promote integrated physiologic improvement to ameliorate metabolic illness, particularly type 2 diabetes. Nevertheless, the therapeutic scope has been limited by unexpectedly inconsistent surgical outcomes. Therefore, the purpose of this study is to overcome the obstacles by determining the core mechanism of conflicting results. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified types of duodenal-jejunal bypass procedures, were compared to comprehend specific surgical patterns from distinctive perspectives. Patients in exclusively nonobese groups are subjected to avoid compounding by weight fluctuations. During intestinal anastomosis, the epithelial identity of the succeeding intestine is replaced by that of the proximal epithelium through altered crosstalk between the epithelium and opposing mesenchymal cells. The rapid turnover rate and compensatory proliferation of the succeeding intestine accelerate the propagation of the replaced epithelium. Propagation of replaced epithelium could provoke inconsistent outcomes of metabolic surgery. The major determinants of the conflicting results of metabolic surgery are inadequate duodenal exclusion and inappropriate length of the biliopancreatic limbs. The replaced enteroendocrine cells during regeneration provoke inconsistent outcomes of metabolic surgery. The critical factors are the type and density of enteroendocrine cells distributed at the terminal end of the preceding proximal intestine.

3D printing is commonly used to create complex objects at a low cost. It has also been applied in the fabrication of metamaterials and metasurfaces, which alter the propagation path of electromagnetic waves. These structures have diverse applications, including enhancing beam direction, improving antenna gain and signal-to-noise ratio, and creating filters and reflectors. Metasurfaces are cheap to fabricate and their use is expected to boost antenna efficiency in 5G telecommunications and beyond. However, accurately characterizing their profile remains a significant challenge. This paper presents a low-cost fully automated 4-axis instrument for microwave metasurface charac-terization, overcoming limitations of manual methods and offering an efficient and accurate approach. This research represents a significant advancement in microwave metasurface characterization, enabling sophisticated techniques to advance wireless communication technolo-gies, as it is the case of the future 5G and millimeter-wave communication systems. The equipment has an approximate cost of $1550 USD and was able to characterize a metalens with a focal distance of 20 cm designed for signals at 30 GHz. It was possible to create 2D and 3D profiles of the intensity distribution focused by the metalens and extract parameters such as the gain (8.05 dB), 3dB depth of focus (11 cm) and full width at half maximum (2.17 cm). The comparison of the measurements with the diffraction calculations of the metalens showed a very good agreement between the in-tensity distributions and the parameters of the metalens.

As the incidence and prevalence of diabetes increases, intervention through dietary education is becoming more important for diabetes control. This systematic review aimed to confirm the ef-fect of dietary intervention education on diabetes control. The study subjects were type 2 diabet-ic patients, and the main outcome variable was glycosylated hemoglobin level (HbA1c). The target studies were randomized controlled trials. Thirty-six studies were included in the analysis, of which 33 were included in the meta-analysis. The effect size between the dietary education and general intervention, was -0.42 (n=5,639, MD=-0.42; 95% CI -0.53 to -0.31) and was signifi-cantly different (Z=7.73, P<.001). When subgroup analyses were performed following the appli-cation periods, intervention methods, and intervention contents, the mean differences in 4–6-month application, individual education, diet-exercise-psychosocial intervention were -0.51, (n=2,742, 95% CI -0.71 to -0.32), -0.63 (n=627, 95% CI -1.00 to -0.26), and -0.51 (n=3.244, 95% CI -0.71 to -0.32), respectively. Dietary education interventions provided for at least 3 months were highly effective in controlling blood sugar levels. Regarding the education method, individual-ized education was more effective, and for this, contact or non-contact education may be applied. Combining diet, exercise, and psychosocial intervention is more effective than diet education alone.

The steering performance according to the steering angle control was tested by using the active steering bogie developed to reduce excessive wheels and rail wear and noise generated when the railway vehicle run in a curved section. As a result of the test of increasing the steering angle in accordance with the target steering angle in the 300m radius of curvature, the bogie is gradually aligned in the radial steering position, and when the control is carried out to 100% of the target steering angle, the bogie angles of the front and rear bogies appeared almost the same. As the steering angle increased, wheel lateral force and derailment coefficient also decreased. Therefore, the validity of the radial steering position control method applied in this paper was confirmed experimentally. This test results will be used for future research on active steering bogie commercialization.

Although Sn has been intensively studied as one of the most promising anode materials to replace commercialized graphite, its cycling performance and rate performance are still unsatisfactory owing to insufficient control of its large volume change during cycling and poor electrochemical kinetics. Herein, we propose a Sn-TiO2-C ternary composite as a promising anode material to overcome these limitations. The hybrid TiO2-C matrix synthesized via two-step high-energy ball milling effectively regulated the irreversible lithiation/delithiation of the active Sn electrode and facilitated Li-ion diffusion. At the appropriate C concentration, Sn-TiO2-C exhibited significantly enhanced cycling performance and rate capability compared to its counterparts (Sn-TiO2 and Sn-C). Sn-TiO2-C delivers good reversible specific capacities (669 mAh g-1 after 100 cycles at 200 mA g-1 and 651 mAh g-1 after 500 cycles at 500 mA g-1) and rate performance (446 mAh g-1 at 3000 mA g-1). The superiority of Sn-TiO2-C over Sn-TiO2 and Sn-C was corroborated by electrochemical impedance spectroscopy, which revealed faster Li-ion diffusion kinetics in the presence of the hybrid TiO2-C matrix than in the presence of TiO2 or C alone. Therefore, Sn-TiO2-C is a potential anode for next-generation Li-ion batteries.

We report a new fabrication method for a fully stretchable supercapacitor based on single wall carbon nanotube (SWCNT)-coated electrospun rubber nanofibers as stretchable supercapacitor electrodes. The deposition conditions of SWCNT on hydrophobic rubber nanofibers are experimentally optimized to induce a uniform coating of SWCNT. For surfactant-assisted coating of SWCNT, both water contact angle and sheet resistance were the lowest compared to the cases with other surface treatment methods, indicating the most effective coating approach. The excellent electromechanical properties of this electrode under the stretching condition is demonstrated by the measurement of Young’s modulus and normalized sheet resistance. This superb tolerance of the electrode with respect to stretching results from i) high aspect ratios of both nanofiber templates and the SWCNT conductors, ii) highly elastic nature of rubbery nanofiber, and iii) strong adherence of SWCNT-coated nanofiber on the elastic ecoflex substrate. Electrochemical and electromechanical measurements on the stretchable supercapacitor devices reveal that the volumetric capacitance (15.2 F cm-3 at 0.021 A cm-3) of the unstretched state is maintained for strains of up to 40 %. At this level of strain, the capacitance after 1,000 charge/discharge cycles is not significantly reduced. The high stability of our stretchable device suggests potential future applications in various types of wearable energy storage devices.

An identification key to twenty-nine species of Porina known from the country is provided. In addition, new records of Porina interstes, P. nuculastrum, and P. rhaphidiophora are described from the protected rain forests in southern Vietnam. A detailed taxonomic account of each species is provided and supported by its ecology, distribution, and illustrations.

In industrial settings, gears play a crucial role by assisting various machinery functions such as speed control, torque manipulation, and altering motion direction.The malfunction or failure of these gear components can have serious repercussions, resulting in production halts and financial losses. As a result, there is an increasing requirement to monitor the state of these components in order to avoid such issues from occurring. To address this need, research efforts have focused on early defect detection in gears in order to reduce the impact of possible failures. This study focused on analyzing vibration and thermal datasets from two extruder machine gearboxes using an autoencoder Long Short-Term Memory (LSTM) model. The major goal is to implement an outlier detection approach to detect and classify defects. The results of this study highlighted the extraordinary performance of the Autoencoder LSTM model, which achieved an impressive accuracy rate of 94.42% in recognizing malfunctioning gearboxes within the extruder machine system. Furthermore, the study used a thorough global metrics evaluation methodology to further test the model’s dependability and efficacy, consequently substantiating the proposed approach’s validity.

In the era of big data, feature engineering has proved its efficiency and importance in dimensionality reduction and useful information extraction from original features. Feature engineering can be expressed as dimensionality reduction and is divided into two types of methods such as feature selection and feature extraction. Each method has its pros and cons. There are a lot of studies to combine these methods. Sparse autoencoder (SAE) is a representative deep feature learning method that combines feature selection with feature extraction. However, existing SAEs do not consider the feature importance during training. It causes extracting irrelevant information. In this paper, we propose a parallel guiding sparse autoencoder (PGSAE) to guide the information by two parallel guiding layers and sparsity constraints. The parallel guiding layers keep the main distribution using Wasserstein distance which is a metric of distribution difference, and it suppresses the leverage of guiding features to prevent overfitting. We perform our experiments using four datasets that have different dimensionality and number of samples. The proposed PGSAE method produces a better classification performance compared to other dimensionality reduction methods.

In recent years, cancer therapy has witnessed significant advancements, with a focus on personalized and targeted treatment strategies. One promising approach involves the use of stimuli-responsive biomaterials for site-specific drug release. Among these biomaterials, pH, and redox-triggered polymer-nano composites have gained immense attention due to their ability to respond to the specific tumor microenvironment, enhancing therapeutic efficacy while reducing off-target effects. Cancer cells often exhibit anomalous biochemical properties, attributed to lower cytosolic pH (acidic) and elevated redox potential through the epitomized upregulation of undesired genes. Such biological process substantially imbalance the level ions (protons) and biological thiols glutathione (GHS) in the cytoplasm as well as in the subcellular organelles. Superfluous accumulation of ions and redox imbalance is associated with proliferation, invasion, and growth of tumor. Because of high surface area, deep tissue penetration capability, higher hydrophilicity, hydrophobic interior for drug/gene efficient loading, biocompatibility and site-specific targeting efficiency, functionalized polymer nanocomposites are superior to conventional small molecular materials. Paradoxically conventional methods of drug delivery aided therapeutics accompanied with inherent drug/genes are encapsulated in biocompatible carrier or suitable transfecting agents generally suffered with low bioavailability, uncontrolled drug release, low cellular penetration, cellular internalization, toxicity, and poor drug loading efficiency. To overcome these issues, recently various multifunctional nanomaterials were developed, based on synergistic stimuli responsive aided drug release in a specified cellular or subcellular system. High therapeutic efficacy, of nanoparticles (NPs) mainly associated with surface functionalization through biocompatible polymeric materials, site-specific targeting units accompanied with stimuli responsive components. Followed by therapeutically important drug or genetic materials were loaded into NPs either in covalent or non-covalent approach. Intriguingly, combined pH and redox dual stimuli based functional materials specially based on polymeric nanocomposites for cancer therapeutics scarcely reported. This article provides the recent progress in pH and redox-responsive polymer-nano composites for site-specific drug delivery in cancer therapy. It explores design principles, fabrication methods, mechanism of action, and prospects of these dual-stimuli responsive biomaterials.

Switched-mode power supplies (SMPS) often utilize electrolytic capacitors due to their substantial energy density and economical pricing. However, their ability to function at low temperatures is essential for dependable operation in several sectors, including telecommunications, automotive, and aerospace. This study includes an experimental evaluation of how well standard SMPS electrolytic capacitors operate at low temperatures. This paper investigates the suitability of standard electrolytic capacitors used in switched-mode power supplies (SMPS) for low-temperature applications. The experimental evaluation exposed the capacitors to temperatures ranging from - 5 ∘C to - 40 ∘C, assessing capacitance (Cp), impedance (Z), dissipation factor (DF), and equivalent series resistance (ESR) at each temperature. The capacitor’s time-domain electrical signals were analyzed using the Pearson correlation coefficient to extract discriminative features. These features were input into an Artificial Neural Network (ANN) for training and testing. Results indicated a significant impact of low temperatures on capacitor performance. Capacitance decreased with lower temperatures, while ESR and leakage current increased, affecting stability and efficiency. Impedance proved to be a valuable diagnostic tool for identifying potential capacitor failure, showing a 98.44% accuracy drop at - 5 degrees and 88.75% at the peak temperature, indicating proximity to the manufacturer’s specified limit. The study suggests further research and development to improve electrolytic capacitors’ performance in SMPS systems under cold conditions to enhance efficiency and reliability.

The degradation of Proton-exchange membrane fuel cell (PEMFC) gasket materials is crucial in electric vehicles as it can cause hazardous hydrogen fuel leaks, which are usually due to high temperatures, pressures, and hydrogen fuel exposure. Degradation of gasket materials in PEMFC presents a critical concern for electric vehicle safety due to potential hydrogen fuel leaks. This study utilizes finite element analysis (FEA) to assess the suitability of gasket materials for PEMFC applications, focusing on aging and tensile conditions. The dual degradation framework, incorporating contact pressure and von Mises stress, is employed to evaluate Liquid Silicon Rubber (LSR) and Ethylene Propylene Diene Monomer (EPDM) materials. Under aging techniques, the Yeoh model exhibits the least Mean Absolute Percentage Error (MAPE) and computational cost of 0.27 seconds, while the Ogden model records the highest computational cost of 0.89 seconds. In evaluating MAE, Root Mean Square Error (RMSE), and R-squared metrics, LSR and EPDM materials demonstrate respective averages of 0.25%, 0.275%, 0.945%, and 0.815%, 0.685%, 0.77%. Tensile testing (Uniaxial) reveals RMSE and MAE values of 0.30%, 0.40%, and 0.50%, 0.40%, respectively. FEA proves instrumental in identifying suitable gasket materials for PEMFC applications. LSR emerges as the superior choice, demonstrating enhanced FEA modelling performance under aging and tensile conditions. These findings contribute valuable insights to the design and development of improved gasket materials, bolstering the safety and reliability of electric vehicles.

Background: This study explored the effects of a virtual reality exercise program on overweight middle-aged women. Methods: This randomized controlled trial included women 4065 years of age with a body mass index (BMI) of 23 kg/m2 or more living in D city. The virtual reality environment was set up by attaching an IoT sensor to an indoor bicycle and linking it with a smartphone, enabling exercise in an immersive virtual reality through a head-mounted display. Results: In the virtual reality exercise group, the BMI was significantly decreased after the 8-week intervention compared with the baseline value (F=100.806, p<.001). The depression scores were significantly different among the three groups, with the intervention effect being more significant in the virtual reality exercise group than in the indoor bicycle exercise and con-trol groups (F=3.462, p<.001). Furthermore, the levels of exercise fun (F=12.373, p<.001) and exer-cise immersion (F=14.629, p<.001) were significantly higher in the virtual reality exercise group than in the indoor bicycle exercise and control groups. Conclusions: The virtual reality exercise program positively affected the BMI and the levels of depression, exercise fun, and exercise im-mersion in overweight middle-aged women. It is an effective home exercise program for obesity management in this population.

During the recent decades, global warming by greenhouse gas evolution has attracted worldwide attention and evermore strict regulations thereon have become institutionalized as international policies. In the process, more environment-friendly power generation technologies have been developed utilizing fossil fuels with a view to timely commercialization. As one of such “clean coal” technology, Integrated Gasification Fuel Cell system is a promising power generation means and COS hydrolysis reactor is installed downstream of coal syngas to remove acidic gas constituents such as H2S and COS. The most significant design parameters affecting performance of the COS hydrolysis reactor were selected to be GHSV, (catalytic) reaction temperature, and length ratio and numerical modeling was performed considering heat and fluid flow transfer as well as chemical reaction kinetics. Effect of the selected design parameters on the variation of conversion rate and reactant gas mixture concentration were comprehensively investigated to predict performance of COS hydrolysis reactor. Stochastic modeling of reactor performance was finally performed using Monte Carlo simulation and linear regression fitting.

Large epidemiological studies show U-shaped relationships between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality in individuals without atherosclerotic cardiovascular diseases (ASCVD). Association in those with ASCVD by sex is unclear. We examined the association between HDL-C levels and 10-year all-cause mortality in subjects (≥40 years of age) with ASCVD using the 2010 National Health Insurance Service and the National Death Registry of Korea. We categorized HDL-C levels into three groups (low: <40 mg/dL for males, <50 mg/dL for females; high: 40-90 mg/dL for males, 50-90 mg/dL for females; extremely high: >90 mg/dL) and 10 mg/dL intervals. We conducted a sex-stratified and adjusted Cox proportional hazards analysis. Out of 1,711,548 individuals (54% female, mean age 61.4 years), 10-year mortality was observed in 218,252 (12.8%). Males had a higher mortality rate than females (16.2% vs 9.8%; P<0.001). When adjusting for age, body mass index, LDL-cholesterol, triglycerides, hypertension, diabetes, smoking, and alcohol consumption, the low and extremely high HDL-C groups had significantly higher hazard ratios for 10-year mortality compared to the high HDL-C group in males [1.183 (1.166-1.199), 1.359 (1.288-1.434)] and in females [1.153 (1.138-1.169), 1.095 (1.029-1.167)]. The frequency distribution bars for the 10-year mortality rate showed sex-specific nadirs of 50-59 mg/dL in males and 70-79 mg/dL in females. In this ASCVD cohort, the extremely high HDL-C (>90 mg/dL) group had 35.9% and 9.5% higher 10-year mortality risk than the high HDL-C group for males and females, respectively. There was a slightly U-shaped relationship between baseline HDL-C levels and 10-year mortality rate, with earlier inflection in males than in females.

The increasing amount of data transmitted through digital broadcasting and communication channels requires efficient transmission methods that make the most of limited resources such as frequency, time, and power. The layered division multiplexing (LDM) system, which is adopted by the Advanced Television Systems Committee (ATSC) 3.0 standard, is considered one of a solution for achieving efficient transmission. Additionally, the layered time-division multiplexing (LTDM) and time layered division multiplexing (TLDM) systems have been developed as well. These layered transmission systems, utilizing multiple physical layer pipes (PLPs), offer a wide range of services including mobile and rooftop TV. To compare the efficiencies of different layered transmission systems, the article introduces the concept of normalized channel capacity. This measure allows for a fair comparison among the systems by taking into account the specific channel capacity requirements of each service. By summing the normalized channel capacities, a method is proposed to select the most efficient transmission system among the four systems: LDM, LTDM, TLDM, and time division multiplexing (TDM). The Lagrange multiplier method is employed to find the parameters that maximize the sum of the normalized channel capacities in these systems. Through simulations conducted with the determined parameters, it is demonstrated that the LDM system exhibits the highest efficiency among the four systems.

To enhance the overall reliability of the power system, engineers have redirected their focus toward health monitoring and early detection of faults in transformers. Among these faults, transformer core defects demand particular attention. While fault simulation using software has traditionally been the preferred approach, these methods suffer from data inaccuracies in real-world conditions. Consequently, conducting actual experimental setups with induced faults is imperative to investigate core issues. This study uses Hilbert Transform (HT) as a signal processing technique to extract crucial data characteristics, thereby enhancing the performance of the classifier model. The research involves analyzing electric current signals from a single-phase 1kVA transformer. A comparative assessment of our proposed model was conducted using raw data and Fast Fourier Transform (FFT), evaluating accuracy, precision, recall, F1-score, and computational time. The results demonstrate a significant improvement in all metrics for the classifier models, particularly the k-nearest neighbor (KNN) algorithm, which exhibited values of 83.89%, 84.39%, 83.89%, 83.79%, and 0.0156 seconds, respectively. Future work aims to extend this analysis under different loading conditions.

Coronavirus-infected diseases have posed great threats to human health. In past years, highly infectious coronavirus-induced diseases, including COVID-19, SARS, and MERS, have resulted in world-wide severe infections. Our literature annotations identified 110 chemical drugs and 26 antibodies effective against at least one human coronavirus infection in vitro or in vivo. Many of these drugs inhibit viral entry to cells and viral replication inside cells or modulate host immune responses. Many antimicrobial drugs, including antimalarial (e.g., chloroquine and mefloquine) and antifungal (e.g., terconazole and rapamycin) drugs as well as antibiotics (e.g., teicoplanin and azithromycin) were associated with anti-coronavirus activity. A few drugs, including remdesivir, chloroquine, favipiravir, and tocilizumab, have already been reported to be effective against SARS-CoV-2 infection in vitro or in vivo. After mapping our identified drugs to three ontologies ChEBI, NDF-RT, and DrON, many features such as roles and mechanisms of action (MoAs) of these drugs were identified and categorized. For example, out of 57 drugs with MoA annotations in NDF-RT, 47 have MoAs of different types of inhibitors and antagonists. A total of 29 anticoronaviral drugs are anticancer drugs with the antineoplastic role. Two clustering analyses, one based on ChEBI-based semantic similarity, the other based on drug chemical similarity, were performed to cluster 110 drugs to new categories. Moreover, differences in physicochemical properties among the drugs were found between those inhibiting viral entry and viral replication. A total of 163 host genes were identified as the known targets of 68 anti-coronavirus drugs, resulting in a network of 428 interactions among these drugs and targets. Chlorpromazine, dasatinib, and anisomycin are the hubs of the drug-target network with the highest number of connected target proteins. Many enriched pathways such as calcium signaling and neuroactive ligand-receptor interaction pathways were identified. These findings may be used to facilitate drug repurposing against COVID-19.

Multidrug resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach; we have modified the antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh3) moiety via ester- (CFX-ester-PPh3) and amide-coupling (CFX-ester-PPh3), to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh3 and CFX-amide-PPh3 showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (MRSA) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with an MIC values of 11.12 µg/mL for CFX-ester-PPh3 and 2.78 µg/mL for CFX-amide-PPh3. The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh3. In the sub-MIC, CFX derivates induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria, through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.

As symbionts of fungi and algae, lichens produce a variety of secondary products which pharmacological activities. This study aimed to investigate the anti-inflammatory activities of Heterodermia hypoleuca and its main compound, atraric acid. The results confirmed that atraric acid could regulating induced pro-inflammatory cytokine, nitric oxide, induced nitric oxide synthase and cyclooxygenase-2 expression by lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Means while, atraric acid down-regulated expression of phosphorylated IκB, ERK and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results show that atraric acid has an anti-inflammatory effect and its molecular mechanism may be involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its value as a potential therapeutic for inflammatory diseases.

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of this study was to establish a reliable quantitative structure-activity relationship (QSAR) model to correlate the structures and physicochemical properties of various SCs with their CB1R-binding affinities. We prepared 15 SCs and their derivatives (tetrahydrocannabinol [THC], naphthoylindoles, and cyclohexylphenols) and determined their binding affinity to CB1R, which is known as a dependence-related target. We calculated the molecular descriptors for dataset compounds using an R/CDK (R package integrated with CDK, version 3.5.0) toolkit to build QSAR regression models. These models were established and statistical evaluations were performed using the mlr and plsr packages in R software. The most reliable QSAR model was obtained from the partial least squares regression method via external validation. This model can be applied in vivo to predict the addictive properties of illicit new SCs. Using a limited number of dataset compounds and our own experimental activity data, we built a QSAR model for SCs with good predictability. This QSAR modeling approach provides a novel strategy for establishing an efficient tool to predict the abuse potential of various SCs and to control their illicit use.

The appropriate carbapenem use is a critical concern for patient safety, public health, and a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprising of 1,350 decedents. Carbapenem use was universally restricted by computerised authorisation at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last 2 weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was 7 days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) without ID consults, 194 (58.2%) were assessed as “not optimal”: 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients within their last days of life, a majority of whom do not require it.

We produced a recombinant eel luteinizing hormone (rec-eel LH) analog with high potency in Chinese hamster ovary DG44 (CHO DG44) cells. The eel LH mutant (LH-M), which had a linker comprising the equine chorionic gonadotropin (eCG) β-subunit carboxyl-terminal peptide (CTP) region (amino acids 115 to149), was inserted between the β-subunit and α-subunit of wild-type tethered eel LH (LH-wt). Monoclonal cells transfected with the eel LH-wt and eel LH-M plasmids were isolated from five and nine clones of CHO DG44 cells, respectively. The secreted quantities abruptly increased on day 3, with peak levels of 5,000–7,500 ng/mL on day 9. The molecular weight of eel LH-wt was 32–36 kDa while that of eel LH-M increased to approximately 38–44 kDa, indicating the detection of two bands. Treatment with peptide N-glycanase F decreased the molecular weight by approximately 8 kDa. The oligosaccharides at the eCG β-subunit O-linked glycosylation sites were appropriately modified post-translation. The EC50 value and maximal responsiveness of eel LH-M increased by approximately 2.90- and 1.29-fold, respectively, indicating that the mutant exhibited more potent biological activity than eel LH-wt. Phosphorylated extracellular regulated kinase (pERK1/2) activation resulted in a sharp peak 5 min after agonist treatment, with a rapid decrease thereafter. These results indicate that the new rec-eel LH analog which contains the eCG β-subunit CTP linker comprising O-linked glycosylation sites, had more potent activity than the wild-type in vitro. Taken together, this new eel LH analog can be produced in large quantities using a stable CHO DG44 cell system.