Identification and validation of cuproptosis-related genes in acetaminophen-induced liver injury using bioinformatics analysis and machine learning.

Background: Acetaminophen (APAP) is commonly used as an antipyretic analgesic. However, acetaminophen overdose may contribute to liver injury and even liver failure. Acetaminophen-induced liver injury (AILI) is closely related to mitochondrial oxidative stress and dysfunction, which play critical roles in cuproptosis. Here, we explored the potential role of cuproptosis-related genes (CRGs) in AILI. Methods: The gene expression profiles were obtained from the Gene Expression Omnibus database. The differential expression of CRGs was determined between the AILI and control samples. Protein protein interaction, correlation, and functional enrichment analyses were performed. Machine learning was used to identify hub genes. Immune infiltration was evaluated. The AILI mouse model was established by intraperitoneal injection of APAP solution. Quantitative real-time PCR and western blotting were used to validate hub gene expression in the AILI mouse model. The copper content in the mouse liver samples and AML12 cells were quantified using a colorimetric assay kit. Ammonium tetrathiomolybdate (ATTM), was administered to mouse models and AML12 cells in order to investigate the effects of copper chelator on AILI. Results: The analysis identified 7,809 differentially expressed genes, 4,245 of which were downregulated and 3,564 of which were upregulated. Four optimal feature genes (OFGs; SDHB, PDHA1, NDUFB2, and NDUFB6) were identified through the intersection of two machine learning algorithms. Further nomogram, decision curve, and calibration curve analyses confirmed the diagnostic predictive efficacy of the four OFGs. Enrichment analysis indicated that the OFGs were involved in multiple pathways, such as IL-17 pathway and chemokine signaling pathway, that are related to AILI progression. Immune infiltration analysis revealed that macrophages were more abundant in AILI than in control samples, whereas eosinophils and endothelial cells were less abundant. Subsequently, the AILI mouse model was successfully established, and histopathological analysis using hematoxylin-eosin staining along with liver function tests revealed a significant induction of liver injury in the APAP group. Consistent with expectations, both mRNA and protein levels of the four OFGs exhibited a substantial decrease. The administration of ATTAM effectively mitigates copper elevation induced by APAP in both mouse model and AML12 cells. However, systemic administration of ATTM did not significantly alleviate AILI in the mouse model. Conclusion: This study first revealed the potential role of CRGs in the pathological process of AILI and offered novel insights into its underlying pathogenesis.

Exploring the prognostic impact of differences in treatment strategies for SCLC with different histologies and prognostic factors for C-SCLC: A SEER population-based study.

Background: Combined small cell lung cancer (C-SCLC) is a rare type of small cell lung cancer (SCLC), and it is controversial whether to choose the same treatment regimen as SCLC due to its multiple histologic components. Study methods and results: Records of patients with small cell lung cancer diagnosed between 2010 and 2020 were extracted using the SEER database. The OS of patients with different histological types under the same staging and treatment regimen was analyzed. It was found that early-stage (stage IA-IIA) surgical treatment, systemic chemotherapy alone, and chemoradiotherapy were more efficacious than C-SCLC and P-SCLC in patients with limited-stage (P = 0.054, P = 0.001, P = 0.019). In patients with extensive staging, the OS of patients with systemic chemotherapy regimens differed (P = 0.045) and was better in C-SCLC than in P-SCLC. We further explored the treatment strategy for patients with C-SCLC, which was shown by a COX regression model based on prognostic factors screened by Random Forest and LASSO regression models. Surgery, radiotherapy, and chemotherapy would be beneficial for survival. In a subgroup analysis based on stage and treatment regimen, it was shown that patients with early staging (stage IA-IIA) had a better prognosis with surgery (P < 0.001); in patients with extensive staging, chemoradiotherapy was favorable to the patient's prognosis (P = 0.022). Conclusion: Both limited-stage and extensive-stage C-SCLC patients are more sensitive to chemotherapy than P-SCLC patients. Patients with C-SCLC who have access to surgery should undergo surgery as early as possible, while chemoradiotherapy is recommended for patients with extensive staging. Patient age, gender, tumor size, surgery, chemotherapy, radiotherapy, and metastasis may individually affect patient prognosis.

A narrative review of acute pancreatitis-induced splanchnic vein thrombosis: from pathogenesis to clinical management.

Acute pancreatitis-induced splanchnic vein thrombosis (APISVT) is an important sequela complication of acute pancreatitis, which may cause poor prognosis, such as severe gastrointestinal hemorrhage, bowel ischemic necrosis and liver failure. However, its mechanism remains uncertain, and there is not a general consensus on the management. In this study, we reviewed the latest academic publications in APISVT, and discussed its pathogenesis, clinical presentation, adverse outcome and treatment, especially focused on the role of anticoagulant therapy. It was indicated that anticoagulation therapy can significantly elevate thrombus recanalization and reduce the incidence of complications and mortality with no increase of bleeding. Actually, as most of these studies were retrospective analyses and prospective studies included small samples, the conclusion remains controversial. Thus, well-designed randomized controlled trials are urged to verify the effectiveness and safety of anticoagulation therapy for APISVT.

Monomer Emission Mechanism Research of Tetraphenylethene Derivative with Supramolecular Self-Assembly in Polymer Microspheres.

The monomer emission property of the tetraphenylethene (TPE) derivative is rarely reported, and its photoluminescence (PL) mechanism related to supramolecular self-assembly needs further in-depth research. Two long alkyl chain modified derivatives, the TPE derivative (TPE-C10) and pyrene derivative (Pyrene-C10), are designed and synthesized, which possess similar supramolecular assembly behavior but exhibit different PL properties. TPE-C10 not only forms self-assembly morphologies with monomer emission but also emits aggregation-induced emission (AIE). Moreover, the polymer microspheres containing TPE-C10 and Pyrene-C10 are prepared, which can dissolve or swell in different organic solvents. The changed binding effect of polymer chains achieves the luminescence transformation of TPE-C10 from AIE to monomer emission. This work hopefully can enrich luminescent materials based on the monomer emission of the TPE derivative and provide a new method for mechanism studies about supramolecular self-assembly and luminescence.

Serum cholinesterase as a new nutritional indicator for predicting weaning failure in patients.

Aim: The objective of this study is to examine the correlation between patient serum cholinesterase (SCHE) concentration and weaning failure in the context of invasive mechanical ventilation (IMV), as well as to identify predictors of ventilator weaning failure. Additionally, this study investigates the potential relationship between SCHE and nutritional risk for developing more effective weaning strategies. Method: A retrospective observational study was conducted. The sample was collected from 227 patients with IMV over 48 h who underwent SBT before weaning. Relevant experimental samples and data collection were analyzed at the time of patient admission and before the initiation of the SBT. The correlation between SCHE and weaning failure was determined by multifactorial logistic regression and propensity matching scores. Results: Weaning was successful in 127 patients and failed in 100 patients. Depending on the difficulty of weaning, 55 of these patients had difficulty in weaning and 45 had long-term weaning. In the crude cohort, experimental data collected on the day of SBT showed that SCHE concentrations were higher in patients with successful weaning than in those with failed weaning (4,514 u/l vs. 3,190 u/l p < 0.01). The critical value for predicting weaning failure was SCHE 3,228 u/l (p < 0.01). Ventilator weaning failure was predicted by multifactorial logistic regression analysis of SCHE, heart rate, and PaO2 before SBT, with SCHE predicting ventilator weaning failure (AUC 0.714; 95% CI 0.647-0.782) better than heart rate (AUC 0.618; 95% CI 0.545-0.690), PaO2 (AUC 0.59; 95% CI 0.515-0.664). After propensity-matched scores, SCHE remained an independent predictor of weaning failure (p = 0.05). And the SCHE concentration was strongly correlated with the patient's weaning difficulties (p < 0.01). The Nutrition Risk in Critically Ill (NUTRIC) score was also significantly correlated with SCHE according to Spearman's correlation analysis (p < 0.01). Conclusion: Our study revealed that the patients who experienced weaning failure exhibited lower SCHE values compared to those who successfully underwent weaning. Before spontaneous breathing trial (SBT), SCHE, heart rate, and PaO2 were identified as independent predictors of weaning failure. Following propensity score matching (PSM), SCHE and heart rate remained independent predictors. Patients with SCHE levels below 3,228 u/l should undergo careful evaluation before weaning. Our findings suggest that malnutrition may be a contributing factor to weaning failure in patients.

Coupling effect of vehicle wake and jet flow on the dispersion characteristics and dilution efficiency of pollutants in urban highway tunnels.

The pollutants emitted by traveling vehicles are prone to accumulation inside urban highway tunnels, which poses a serious threat to the driving safety and health of passengers. This study employed the dynamic mesh method to simulate a traveling vehicle and investigated the coupling effect of vehicle wake and jet flow on the dispersion characteristics of pollutants in urban highway tunnels. To ensure the accuracy of the numerical simulation results, the turbulence model (realizable k-ε model) and dynamic mesh model were validated through field tests. The results revealed that jet flow can disrupt the large-scale longitudinal vortices pattern in the wake region, whereas vehicle wake can simultaneously weaken the entrainment strength of jet flow. The jet flow was found to be decisive in the space with a height greater than 4 m, whereas the vehicle wake intensity was considerably stronger at the bottom space of the tunnel, leading to the accumulation of pollutants in the passenger breathing zone. To evaluate the effect of jet fans on pollutants in the breathing zone, an innovative dilution efficiency was proposed. The dilution efficiency can be significantly affected by the intensity of vehicle wake and turbulence. Moreover, the dilution efficiency of alternative jet fans was better than that of traditional jet fans.

Multi-layered cement-hydrogel composite with high toughness, low thermal conductivity, and self-healing capability.

The inherent quasi-brittleness of cement-based materials, due to the disorder of their hydration products and pore structures, present significant challenges for directional matrix toughening. In this work, a rigid layered skeleton of cement slurry was prepared using a simplified ice-template method, and subsequently flexible polyvinyl alcohol hydrogel was introduced into the unidirectional pores between neighboring cement platelets, resulting in the formation of a multi-layered cement-based composite. A toughness improvement of over 175 times is achieved by the implantation of such hard-soft alternatively layered microstructure. The toughening mechanism is the stretching of hydrogels at the nano-scale and deflections of micro-cracks at the interfaces, which avoid stress concentration and dissipate huge energy. Furthermore, this cement-hydrogel composite also exhibits a low thermal conductivity (around 1/10 of normal cement) and density, high specific strength and self-healing properties, which can be used in thermal insulation, seismic high-rise buildings and long-span bridges.

Burden of liver cancer due to hepatitis C from 1990 to 2019 at the global, regional, and national levels.

Background: Liver cancer due to hepatitis C (LCDHC) is one of the leading causes of cancer-related deaths worldwide, and the burden of LCDHC is increasing. We aimed to report the burden of LCDHC at the global, regional, and national levels in 204 countries from 1990 to 2019, stratified by etiology, sex, age, and Sociodemographic Index. Methods: Data on LCDHC were available from the Global Burden of Disease, Injuries, and Risk Factors (GBD) study 2019. Numbers and age-standardized mortality, incidence, and disability-adjusted life year (DALY) rates per 100,000 population were estimated through a systematic analysis of modeled data from the GBD 2019 study. The trends in the LCDHC burden were assessed using the annual percentage change. Results: Globally, in 2019, there were 152,225 new cases, 141,810 deaths, and 2,878,024 DALYs due to LCDHC. From 1990 to 2019, the number of incidences, mortality, and DALY cases increased by 80.68%, 67.50%, and 37.20%, respectively. However, the age-standardized incidence, mortality, and DALY rate had a decreasing trend during this period. In 2019, the highest age-standardized incidence rates (ASIRs) of LCDHC were found in high-income Asia Pacific, North Africa and the Middle East, and Central Asia. At the regional level, Mongolia, Egypt, and Japan had the three highest ASIRs in 2019. The incidence rates of LCDHC were higher in men and increased with age, with a peak incidence in the 95+ age group for women and the 85-89 age group for men in 2019. A nonlinear association was found between the age-standardized rates of LCDHC and sociodemographic index values at the regional and national levels. Conclusions: Although the age-standardized rates of LCDHC have decreased, the absolute numbers of incident cases, deaths, and DALYs have increased, indicating that LCDHC remains a significant global burden. In addition, the burden of LCDHC varies geographically. Male and older adult/s individuals have a higher burden of LCDHC. Our findings provide insight into the global burden trend of LCDHC. Policymakers should establish appropriate methods to achieve the HCV elimination target by 2030 and reducing the burden of LCDHC.

Capecitabine-induced enterocolitis: a case report and pharmacogenetic profile.

Capecitabine is a widely-used antineoplastic drug, a prodrug to 5-fluorouracil which commonly induces gastrointestinal toxicity. Enterocolitis, as a rarely recognized gastrointestinal adverse effect (AE) of capecitabine, is potentially severe and usually results in antitumor treatment withdrawal. For the better management of severe AEs, pharmacogenetics is one promising field. Herein, we describe a case of capecitabine-induced enterocolitis presenting with severe diarrhea in order to improve recognition by clinicians. Moreover, we conduct a pharmacogenetic profile of the patient and review the current studies of gene polymorphisms of 5-fluorouracil-related diarrhea, hoping to offer a reference for further clinical pharmacogenetic practice in predicting capecitabine AEs showing diarrhea as the main symptom.

Prediction of Temperature Distribution in Concrete under Variable Environmental Factors through a Three-Dimensional Heat Transfer Model.

Temperature distribution in concrete is significant to the concrete structure's macro properties and different factors affect the heat transfer in concrete, and therefore influence the temperature distribution. This work established a three-dimensional transient heat transfer model coupled with various environmental factors, using the finite element method for calculating the results and real-measured data for testing accuracy. In addition, a sensitivity evaluation of various factors was conducted. Due to various environmental factors, the results revealed that the prediction of temperature distribution in concrete by the three-dimensional model had great accuracy with an error of less than 4%. A particular hysteresis effect of temperature response in the concrete existed. Considering heat transfer in different spatial directions, the model can predict the temperature change of each spatial point instead of the spatial surface in different depths, proving the shortcomings of a one-dimensional heat transfer model. A greater solar radiation intensity caused a more significant temperature difference on the concrete surface: the surface temperature difference in July was twice as significant as that in December. Wind speed had a cooling effect on the concrete surface, and stronger wind speed accompanied with a stronger cooling effect made the surface temperature closer to the ambient temperature. Material properties had different effects on the temperature distribution of the surface part and internal part: the specific heat capacity determined the speed of the outer layer temperature change while the thermal conductivity determined the speed of the inner layer temperature change.

A Novel Zein-Based Composite Nanoparticles for Improving Bioaccessibility and Anti-Inflammatory Activity of Resveratrol.

A microbial transglutaminase-induced cross-linked sodium caseinate (MSC) was used to stabilize zein nanoparticles, and the study was to investigate whether zein-MSC nanoparticles (zein-MSC NPs) can be used as an encapsulation carrier for resveratrol. A group of resveratrol-loaded zein-MSC nanoparticles (Res-zein-MSC NPs) with varying zein to Res mass ratios was first prepared. The particle sizes and zeta-potentials were in the ranges from 215.00 to 225.00 nm and from -29.00 to -31.00 mV. The encapsulation efficiency (EE) of Res was also influenced by the zein to Res mass ratio, and the encapsulated Res existed in an amorphous form. The major interactions between Res and zein-MSC NPs were hydrogen bonding and hydrophobic interaction. Furthermore, compared with free Res, the photo-stability and bioaccessibility of Res-zein-MSC NPs were significantly improved. The cellular studies also showed that Res-zein-MSC NPs exhibited lower cytotoxicity and desirable anti-inflammatory activity.

Novel Nano-Precursor Inhibiting Material for Improving Chloride Penetration Resistance of Concrete: Evaluation and Mechanism.

Durability improvement is always important for steel-concrete structures exposed to chloride salt environment. The present research investigated the influence of a novel nano-precursor inhibiting material (NPI), organic carboxylic acid ammonium salt, on the mechanical and transport properties of concrete. The NPI caused a slight reduction in the strength of concrete at later ages. NPI significantly decreased water absorption and slowed down the speed of water absorption of concrete. In addition, the NPI decreased the charge passed and the chloride migration coefficient, and the results of the natural chloride diffusion showed that the NPI decreased the chloride concentration and the chloride diffusion coefficient. The NPI effectively improved the resistance of chloride penetration into testing concrete. The improvement in the impermeability of concrete was ascribed to the incorporation with the NPI, which resulted in increasing the contact angle of cement pastes. The contact angle went up from 17.8° to 85.8° for 0% and 1.2% NPI, respectively, and cement pastes became less hydrophilic. Some small pore throats were unconnected. Besides, the NPI also optimized the pore size distribution of hardened cement paste.

Chemical Composition Profiling and Biological Activities of Phenolic Compounds in Eleven Red Sorghums.

The profiles of soluble and insoluble phenolic compounds in 11 commercial red sorghums (B11, B12, B13, B14, J124, J127, J138, J140, J142, J152, and J158) were investigated using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) analysis. A total of 48 phenolic compounds including 35 phenolic acids and their derivatives, 12 flavonoids, and 1 proanthocyanidin were identified, and 8 phenolic compounds were reported for the first time in sorghums. Four major 3-deoxyanthocyanidins were also quantified, with their soluble forms accounting for 99.75-99.87% of the total contents. Pearson's correlation analyses indicated that 3-deoxyanthocyanidins significantly contributed to the antioxidant capacities of the red sorghums and that 5-methoxy-luteolinidin showed the strongest correlation. Besides, the soluble phenolic fraction of B13 dose-dependently inhibited the proliferation of Caco-2 cells and the secretion of IL-1ß and NO in RAW264.7 macrophages, which might be attributed to its relatively high total phenolic (TPC), flavonoid (TFC), and proanthocyanidin content (TPAC) values and radical scavenging capacities.

Evidence for lack of transmission by close contact and surface touch in a restaurant outbreak of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease that has become a global pandemic. Close contact plays an important role in infection spread, while fomite may also be a possible transmission route. Research during the COVID-19 pandemic has identified long-range airborne transmission as one of the important transmission routes although lack solid evidence. METHODS: We examined video data related to a restaurant associated COVID-19 outbreak in Guangzhou. We observed more than 40,000 surface touches and 13,000 episodes of close contacts in the restaurant during the entire lunch duration. These data allowed us to analyse infection risk via both the fomite and close contact routes. RESULTS: There is no significant correlation between the infection risk via both fomite and close contact routes among those who were not family members of the index case. We can thus rule out virus transmission via fomite contact and interpersonal close contact routes in the Guangzhou restaurant outbreak. The absence of a fomite route agrees with the COVID-19 literature. CONCLUSIONS: These results provide indirect evidence for the long-range airborne route dominating SARS-CoV-2 transmission in the restaurant. We note that the restaurant was poorly ventilated, allowing for increasing airborne SARS-CoV-2 concentration.

Effects of the Sn100 kVp Tube Voltage Mode on the Radiation Dose and Image Quality of Dual-Source Computed Tomography Pulmonary Angiography.

OBJECTIVE: This study aimed to investigate the effects of the Sn100 kVp tube voltage mode on the image quality and radiation dose of computed tomography pulmonary angiography (CTPA). METHODS: A total of 145 patients who underwent CTPA were randomly divided into five groups: control group (120 kVp, 150 mAs), test group A (Sn100 kVp, 270 mAs), test group B (120 kVp, 30 mAs), test group C (70 kVp, 150 mAs), and test group D (80 kVp, 70 mAs). After image post-processing, the image quality and radiation dose of each group were analyzed. RESULTS: The computed tomography values of images in the four test groups were more than 250 HU, which met the criteria for diagnosis. The signal-to-noise ratio and contrast-to-noise ratio of the images in the four test groups were lower than those in the control group. The radiation dose in each test group was lower than in the control group. The radiation dose was lowest in test group A. CONCLUSION: The Sn100 kVp energy spectrum purification protocol can meet the requirements for clinical diagnosis, ensure image quality, and reduce the dose of radiation that patients receive.

Associations of bedroom air temperature and CO2 concentration with subjective perceptions and sleep quality during transition seasons.

This field study aimed to investigate naturally ventilated bedroom environment and its effects on subjective perception and sleep quality. Totally, 104 healthy subjects living in urban areas of Beijing participated in the study for one night during transition seasons. Bedroom environment parameters, including temperature, relative humidity, and CO2 concentration, were recorded before and during sleep. Objective sleep quality was measured by Fitbit Alta 2, a wrist-type actigraphy sensor. Subjective assessments were collected by paper-based questionnaires on sleep quality and environmental perceptions. The results showed that neutral temperature for waking state (before sleep) was estimated to be 23.8°C while for sleep state it was 26.5°C. Furthermore, pre-sleep thermal sensation vote was found to be positively correlated with deep sleep percentage. Indoor air quality was correlated with sleep quality as indicated by statistically significant correlations between odor intensity assessment, air quality acceptability, average nightly CO2 concentration, and measures of sleep quality. For naturally ventilated bedrooms during transition seasons with a mild outdoor climate, present findings suggest that a bedroom with slightly warm pre-sleep environment than neutral, and with high ventilation as indicated by low indoor CO2 concentration, could be beneficial for sleep quality of residents.

Environmental perceptions, mental performance, and physiological responses of people with respiratory allergies exposed to reduced Indoor Air Quality.

To investigate the need of allergic population for indoor environment quality, exposure effects of poor air quality on subjects with respiratory allergies were compared with those on healthy people, including perceptual responses, health symptoms, mental performance, and physiological responses. The experimental intervention was with and without ventilation at thermally neutral rooms, creating two exposure conditions indicated by CO2 concentration ranges of 502 to 3297 ppm (2438 ± 1527 ppm) and 517 to 5687 ppm (3615 ± 1527 ppm). 63 subjects (32 allergic subjects and 31 non-allergic subjects) were exposed to both conditions for 3 hours. The main results suggested that, compared with healthy people, people with respiratory allergy seem to be more sensitive or less acceptable to reduced air quality polluted by occupants during instantaneous exposure. Besides, the allergic group performed worse in cognitive tests than non-allergic group. After 3 hours of continuous exposure, people with respiratory allergy reported stronger intensity of respiratory irritations and seemed to suffer more inflammation indicated by a higher level of interleukin 1L-1ß.

Investigation on the Effect of Hydroxyapatite Nanorod on Cement Hydration and Strength Development.

This work investigated the effect of hydroxyapatite (HA) nanorods on the strength development and hydration of cement. Undispersed HA nanorods (HA-UD) and dispersed HA nanorods (HA-DN) were prepared by atom-efficient neutralization. The strength of mortars modified by HA nanorods was tested, as well as their compatibility with supplementary cementitious material. The hydration of HA-modified cement pastes was characterized via in situ X-ray diffraction, isothermal calorimetry and scanning electron microscopy. As the results suggest, the undispersed HA-DN caused a considerable increase in superplasticizer demand to achieve the same level of flow. Both HA nanorods showed a significant accelerating effect on early hydration, with approximately 100% strength enhancement at 12 h at 2.0% dosage. The effect on early strength of the nanorods is retained in systems with up to 30% fly ash in the binder mass. According to the characterizations, the rate of the hydration reaction in the acceleration period was enhanced by HA nanorods, and C3S consumption was also increased. In all of the testing situations, HA-DN showed superior performance, likely due to improved spatial distribution of the hydroxyapatites. The results suggest that proper dispersion of the nanorods is necessary to optimize its performance.

Comparison of Different Approaches for Testing Sorption by a Superabsorbent Polymer to Be Used in Cement-Based Materials.

The absorption and desorption behavior of superabsorbent polymer (SAP) can influence various properties of cementitious materials. Therefore, it is essential to know these performances of SAP prior to implementation in cement-based materials. In this paper, two types of SAP with different chemical compositions were tested in free liquid (deionized water and cement filtrate) and cement paste. Five absorption test methods were considered, including the tea-bag method, the filtration method, the centrifuge method, the suction filtration method, and the slump flow method. The results show that the absorptivity of SAP A73 and SAP N in cement paste by the slump flow method are about 21 g/g and 7 g/g, respectively. In addition, the centrifuge method and suction filtration method give more accurate absorption values when compared to the tea-bag method and filtration method due to their effectiveness in removing inter-particle liquid. Though the absorptivity obtained by the tea-bag method is higher than the centrifuge method and suction filtration method, it is still a good pre-test method to reveal the performance of SAP used in cementitious materials due to time-saving and simple setups.