Relationship of long-term exposure to air pollutant mixture with metabolic-associated fatty liver disease and subtypes: A retrospective cohort study of the employed population of Southwest China.

BACKGROUND: While evidence suggests that PM2.5 is associated with overall prevalence of Metabolic (dysfunction)-Associated Fatty Liver Disease (MAFLD), effects of comprehensive air pollutant mixture on MAFLD and its subtypes remain unclear. OBJECTIVE: To investigate individual and joint effects of long-term exposure to comprehensive air pollutant mixture on MAFLD and its subtypes. METHODS: Data of 27,699 participants of the Chinese Cohort of Working Adults were analyzed. MAFLD and subtypes, including overweight/obesity, lean, and diabetes MAFLD, were diagnosed according to clinical guidelines. Concentrations of NO3-, SO42-, NH4+, organic matter (OM), black carbon (BC), PM2.5, SO2, NO2, O3 and CO were estimated as a weighted average over participants' residential and work addresses for the three years preceding outcome assessment. Logistic regression and weighted quantile sum regression were used to estimate individual and joint effects of air pollutant mixture on presence of MAFLD. RESULTS: Overall prevalence of MAFLD was 26.6 % with overweight/obesity, lean, and diabetes MAFLD accounting for 92.0 %, 6.4 %, and 1.6 %, respectively. Exposure to SO42-, NO3-, NH4+, BC, PM2.5, NO2, O3and CO was significantly associated with overall MAFLD, overweight/obesity MAFLD, or lean MAFLD in single pollutant models. Joint effects of air pollutant mixture were observed for overall MAFLD (OR = 1.10 [95 % CI: 1.03, 1.17]), overweight/obesity (1.09 [1.02, 1.15]), and lean MAFLD (1.63 [1.28, 2.07]). Contributions of individual air pollutants to joint effects were dominated by CO in overall and overweight/obesity MAFLD (Weights were 42.31 % and 45.87 %, respectively), while SO42- (36.34 %), SO2 (21.00 %) and BC (12.38 %) were more important in lean MAFLD. Being male, aged above 45 years and smoking increased joint effects of air pollutant mixture on overall MAFLD. CONCLUSIONS: Air pollutant mixture was associated with MAFLD, particularly the lean MAFLD subtype. CO played a pivotal role in both overall and overweight/obesity MAFLD, whereas SO42- were associated with lean MAFLD.

Exploring the causal relationships and mediating factors between depression, anxiety, panic, and atrial fibrillation: A multivariable Mendelian randomization study.

BACKGROUND: Atrial fibrillation is a significant cardiovascular disease, and the increased risk of its occurrence may be influenced by mental disorders. Currently, the causal relationship between them remains controversial. Our aim is to ascertain the relationship between atrial fibrillation and mental disorders including depression, anxiety, and panic, as well as the risk factors mediating this relationship, through the judgment of genetic susceptibility. METHODS: We utilized the summarized statistics from nine large-scale genome-wide association studies (in European populations), including depression (PGC, N = 807,553), anxiety (FinnGen, N = 429,209), panic (PGC, N = 230,878), diabetes (UK Biobank, N = 655,666), smoking (IEU, 607,291), hypertension (UK biobank, N = 463,010), obstructive sleep apnea (IEU, N = 476,853), obesity (UK biobank, N = 463,010), and AF (IEU, N = 1,030,836). By applying bidirectional two-sample Mendelian randomization and multivariable Mendelian randomization to depression, anxiety, panic, and AF, we analyzed their causal relationships and the independent influence of specific risk factors. Furthermore, a two-step MR approach was used to assess the mediating effects of diabetes, smoking, hypertension, obstructive sleep apnea, and obesity. RESULTS: Results from the Two-Sample Mendelian Randomization Inverse Variance Weighted Random Effects Model show: the occurrence of genetically predicted depression is related to an increased risk of atrial fibrillation (AF) (OR: 1.073; [95 % CI: 1.005-1.146] P < 0.05), and panic is more significantly associated than depression (OR: 1.017; [95 % CI: 1.008-1.027] P < 0.001), while anxiety has no causal relationship with the occurrence of AF (OR: 1.023; [95 % CI: 0.960-1.092], P > 0.05), and AF is not significantly related to the occurrence of depression, anxiety, or panic (P > 0.05). After correcting for the other two risk factors using multivariable Mendelian randomization, depression remains significantly related to the occurrence of AF (ß: 0.075; 95 % CI: [0.006, 0.144], P < 0.05), while panic and anxiety are not related to the occurrence of AF. Among them, the risk factors for AF occurrence, hypertension and obesity, are mediators between depression and AF, with mediation proportions of 74.9 % and 14.3 %, respectively. The mediating effects of diabetes, smoking, and obstructive sleep apnea were found to be not statistically significant. The above results are robust after sensitivity analysis. CONCLUSION: Our results identified that the genetic susceptibility to depression is an independent risk factor for the occurrence of AF, and that hypertension and obesity can mediate this process. Panic also poses some risk to the onset of AF. This demonstrates that controlling hypertension and obesity for emotional management is of great importance in preventing the occurrence of AF.

Recrystallized resistant starch by encapsulation with konjac glucomannan: Structural changes, digestibility, and its effect on glucose response and short-term satiety in mice.

The effects of the structure and digestibility of konjac glucomannan (KGM)-recrystallized resistant starch complex (KRS3) on the glycemic response and short-term satiety in mice were investigated. KRS3 samples were prepared by recrystallized debranched starch (RS3) at 50 °C, and then combined with KGM. The RS3 and KRS3 samples displayed an A-type pattern and maintained peak temperature values above 110 °C. With an increase in KGM, the swelling power and apparent viscosity of KRS3 increased. The results of in vitro and in vivo digestion revealed that KRS3 with a resistant starch content ranging from 69.4 % to 78.8 % could effectively maintain postprandial blood glucose levels. KRS3, particularly with 0.5 % KGM, slowed gastric emptying of mice from 82.7 % to 36.6 % and intestinal propulsion rate from 60.9 % to 35.3 %, resulting in strong satiety. RS3 combined with KGM could serve as a new approach to develop RS3 based foods with low glycemic responses and high-satiety.

Elemental-Doping-Induced Orbital Redistribution in Conjugated Polymer Boosts Charge-Transfer-Mediated Singlet Oxygen Production.

Beyond the traditional exciton-based energy transfer, carrier-involved charge transfer provides an alternative pathway to overcoming spin restriction in photocatalytic singlet oxygen (1O2) generation. However, the charge-transfer-mediated method usually suffers from insufficient charge-carrier concentration and distribution, which are related to the electronic band structure. Herein, exemplified by polymeric carbon nitride (PCN), we propose an orbital-redistribution strategy for facilitating charge-transfer-mediated 1O2 generation. On the basis of theoretical simulation and spectroscopic characterizations, we demonstrated that the incorporation of bromine could dramatically facilitate the redistribution of the HOMO and LUMO in PCN, resulting in promoted exciton dissociation and adjacent electron/hole distribution. Benefiting from those, bromine-doped polymeric carbon nitride (Br-PCN) exhibited an obvious enhancement in the production of 1O2 via a two-step charge-transfer process. This work not only uncovers a promising method for regulating photoexcitation in polymeric photocatalysts but also sheds new light on photocatalytic 1O2 generation.

Influences of long-term care insurance on pulmonary and urinary tract infections among older people with disability.

BACKGROUND: Pulmonary infection (PI) and urinary tract infection (UTI) have been the most common cause of hospitalization and most frequent infection respectively in older people with disability (OPWD). Long-term care insurance (LTCI) policy, intending to provide services to reduce the disease burden of OPWD, it remains unclear whether LTCI could reduce PI-, and UTI-related hospitalizations. This quasi-experimental study aimed to assess the influences of LTCI on all-cause, especially PI- and UTI-related hospitalizations among OPWD and the variation across sociodemographic characteristics. METHODS: 32,120 participants in the Chengdu Long-term Care Insurance cohort were considered the intervention group, and 2,704 not covered by the LTCI were in the control group. A total of 3,134,160 hospitalization records were collected between January 2014 and June 2021. A doubly robust difference-in-differences (DID) method was used to estimate the average treatment effect on the treated (ATT), indicating the average effect of LTCI on intervention group. RESULTS: The average monthly all-cause, PI-, and UTI-related hospitalization rates were 16.3%, 4.0% and 0.5% in the intervention group, respectively, and were 19.3%, 3.9% and 0.5% in the control group, respectively. Under LTCI, all-cause (ATT [95% CI]: 7.15% [6.41%, 7.88%]), PI- (3.25% [2.76%, 3.74%]), and UTI-related hospitalizations (0.46% [0.28%, 0.64%]) were decreased. The influences of LTCI became significant after 5 months since the LTCI implementation and remained stable over time. The impact was more pronounced among those with longer coverage. The overall reduction was stronger in those who were not married, lived alone, and resided in institutions. CONCLUSIONS: LTCI may reduce the occurrence of all-cause, PI-, and UTI-related hospitalizations in OPWD, with stronger influences observed over an extended period of implementation. The implementation of LTCI can play a role in reducing the burden of infectious diseases in OPWD and the care burden of families and society.

Triglyceride-Glucose Index is Related to Carotid Artery Plaque in Railway Workers: A Cross-Sectional Study.

Aim: China has the highest rail transportation density in the world. Compared to other occupational populations, railway workers in China face increased risk of chronic non-communicable diseases. This study aims to investigate the relationship between the triglyceride-glucose (TyG) index and carotid artery plaque (CAP) in a population of railway workers in southwest China. Methods: The cross-sectional study was conducted among 3169 railway workers who were categorized into four groups based on TyG index quartiles. The presence of CAP was assessed using carotid Doppler ultrasound. Logistic regression and restricted cubic spline analyses were used to estimate the association between TyG index and CAP, and subgroup analyses were performed based on age, blood pressure, metabolic dysfunction-associated fatty liver disease (MAFLD), smoking, drinking, and physical activity. Results: Participants with higher TyG index quartiles had a higher prevalence of CAP, with 11.63%, 14.11%, 20.20%, and 18.56% from the first to fourth quartile, respectively. The multi-adjusted logistic regression models showed a positive association between TyG index and the risk of CAP (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.06-1.41) when treated as a continuous variable. When analyzed as a categorical variable with increasing TyG index tertiles, the risk of CAP substantially increased with ORs (95% CIs) of 1.22 (0.90-1.65) for the second quartile, 1.70 (1.27-2.28) for the third quartile, and 1.46 (1.08-1.98) for the fourth quartile compared to the lowest quartile. Restricted cubic spline revealed that the association gradually strengthened with the increase of the TyG index below 9.56. Conclusion: TyG index was significantly associated with CAP, notably in populations with elevated quartiles of TyG index among railway workers. Monitoring the TyG index could be a useful risk management strategy for CAP in occupation population.

A Review of Intelligent Assembly Technology of Small Electronic Equipment.

Electronic equipment, including phased array radars, satellites, high-performance computers, etc., has been widely used in military and civilian fields. Its importance and significance are self-evident. Electronic equipment has many small components, various functions, and complex structures, making assembly an essential step in the manufacturing process of electronic equipment. In recent years, the traditional assembly methods have had difficulty meeting the increasingly complex assembly needs of military and civilian electronic equipment. With the rapid development of Industry 4.0, emerging intelligent assembly technology is replacing the original "semi-automatic" assembly technology. Aiming at the assembly requirements of small electronic equipment, we first evaluate the existing problems and technical difficulties. Then, we analyze the intelligent assembly technology of electronic equipment from three aspects: visual positioning, path and trajectory planning, and force-position coordination control technology. Further, we describe and summarize the research status and the application of the technology and discuss possible future research directions in the intelligent assembly technology of small electronic equipment.

Fat mass and obesity-associated factor (FTO)-mediated N6-methyladenosine regulates spermatogenesis in an age-dependent manner.

N6-methyladenosine (m6A) is the most prevalent reversible RNA modification in the mammalian transcriptome. It has recently been demonstrated that m6A is crucial for male germline development. Fat mass and obesity-associated factor (FTO), a known m6A demethylase, is widely expressed in human and mouse tissues and is involved in manifold biological processes and human diseases. However, the function of FTO in spermatogenesis and male fertility remains poorly understood. Here, we generated an Fto knockout mouse model using CRISPR/Cas9-mediated genome editing techniques to address this knowledge gap. Remarkably, we found that loss of Fto in mice caused spermatogenesis defects in an age-dependent manner, resulting from the attenuated proliferation ability of undifferentiated spermatogonia and increased male germ cell apoptosis. Further research showed that FTO plays a vital role in the modulation of spermatogenesis and Leydig cell maturation by regulating the translation of the androgen receptor in an m6A-dependent manner. In addition, we identified two functional mutations of FTO in male infertility patients, resulting in truncated FTO protein and increased m6A modification in vitro. Our results highlight the crucial effects of FTO on spermatogonia and Leydig cells for the long-term maintenance of spermatogenesis and expand our understanding of the function of m6A in male fertility.

Comparison of the prognostic value of a comprehensive set of predictors in identifying risk of metabolic-associated fatty liver disease among employed adults.

OBJECTIVE: Metabolic-associated fatty liver disease (MAFLD) is of concern in employed adults, while the crucial indicators in predicting MAFLD are understudied in this population. We aimed to investigate and compare the prediction performance of a set of indicators for MAFLD in employed adults. METHODS: A cross-sectional study recruiting 7968 employed adults was conducted in southwest China. MAFLD was assessed by abdominal ultrasonography and physical examination. Comprehensive indicators of demographics, anthropometric, lifestyle, psychological, and biochemical indicators were collected by questionnaire or physical examination. All indicators were evaluated for importance in predicting MAFLD by random forest. A prognostic model based on multivariate regression model was constructed to obtain a prognostic index. All indicators and prognostic index were compared to evaluate their prediction performance in predicting MAFLD by the receiver operating characteristic (ROC) curve, calibration plot, and Decision curve analysis (DCA). RESULTS: Triglyceride Glucose-Body Mass Index (TyG-BMI), BMI, TyG, triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C), and TG ranked the top five important indicators, and TyG-BMI performed the most accurate prediction of MAFLD according to the ROC curve, calibration plot and DCA. The area under the ROC curves (AUCs) of the five indicators were all over 0.7, with TyG-BMI (cut-off value: 218.284, sensitivity: 81.7%, specificity: 78.3%) suggesting the most sensitive and specific indicator. All five indicators showed higher prediction performance and net benefit than the prognostic model. CONCLUSION: This epidemiological study firstly compared a set of indicators to evaluate their prediction performance in predicting MAFLD risk among employed adults. Intervention targeting powerful predictors can be helpful to reduce the MAFLD risk among employed adults.

The efficacy of anti-proteolytic peptide R7I in intestinal inflammation, function, microbiota, and metabolites by multi-omics analysis in murine bacterial enteritis.

Increased antibiotic resistance poses a major limitation in tackling inflammatory bowel disease and presents a large challenge for global health care. Antimicrobial peptides (AMPs) are a potential class of antimicrobial agents. Here, we have designed the potential oral route for antimicrobial peptide R7I with anti-proteolytic properties to deal with bacterial enteritis in mice. The results revealed that R7I protected the liver and gut from damage caused by inflammation. RNA-Seq analysis indicated that R7I promoted digestion and absorption in the small intestine by upregulating transmembrane transporter activity, lipid and small molecule metabolic processes and other pathways, in addition to upregulating hepatic steroid biosynthesis and fatty acid degradation. For the gut microbiota, Clostridia were significantly reduced in the R7I-treated group, and Odoribacteraceae, an efficient isoalloLCA-synthesizing strain, was the main dominant strain, protecting the gut from potential pathogens. In addition, we further discovered that R7I reduced the accumulation of negative organic acid metabolites. Overall, R7I exerted better therapeutic and immunomodulatory potential in the bacterial enteritis model, greatly reduced the risk of disease onset, and provided a reference for the in vivo application of antimicrobial peptides.

Dual-modal molecular imaging and therapeutic evaluation of coronary microvascular dysfunction using indocyanine green-doped targeted microbubbles.

Coronary microvascular dysfunction (CMD), which causes a series of cardiovascular diseases, seriously endangers human health. However, precision diagnosis of CMD is still challenging due to the lack of sensitive probes and complementary imaging technologies. Herein, we demonstrate indocyanine green-doped targeted microbubbles (named T-MBs-ICG) as dual-modal probes for highly sensitive near-infrared (NIR) fluorescence imaging and high-resolution ultrasound imaging of CMD in mouse models. In vitro results show that T-MBs-ICG can specifically target fibrin, a specific CMD biomarker, via the cysteine-arginine-glutamate-lysine-alanine (CREKA) peptide modified on the surface of microbubbles. We further employ T-MBs-ICG to achieve NIR fluorescence imaging of injured myocardial tissue in a CMD mouse model, leading to a signal-to-background ratio (SBR) of up to 50, which is 20 fold higher than that of the non-targeted group. Furthermore, ultrasound molecular imaging of T-MBs-ICG is obtained within 60 s after intravenous injection, providing molecular information on ventricular and myocardial structures and fibrin with a resolution of 1.033 mm × 0.466 mm. More importantly, we utilize comprehensive dual-modal imaging of T-MBs-ICG to evaluate the therapeutic efficacy of rosuvastatin, a cardiovascular drug for the clinical treatment of CMD. Overall, the developed T-MBs-ICG probes with good biocompatibility exhibit great potential in the clinical diagnosis of CMD.

Patterning of morphogenetic anisotropy fields.

Orientational order, encoded in anisotropic fields, plays an important role during the development of an organism. A striking example of this is the freshwater polyp Hydra, where topological defects in the muscle fiber orientation have been shown to localize to key features of the body plan. This body plan is organized by morphogen concentration gradients, raising the question how muscle fiber orientation, morphogen gradients and body shape interact. Here, we introduce a minimal model that couples nematic orientational order to the gradient of a morphogen field. We show that on a planar surface, alignment to a radial concentration gradient can induce unbinding of topological defects, as observed during budding and tentacle formation in Hydra, and stabilize aster/vortex-like defects, as observed at a Hydra's mouth. On curved surfaces mimicking the morphologies of Hydra in various stages of development-from spheroid to adult-our model reproduces the experimentally observed reorganization of orientational order. Our results suggest how gradient alignment and curvature effects may work together to control orientational order during development and lay the foundations for future modeling efforts that will include the tissue mechanics that drive shape deformations.

Integrated analysis of ferroptosis-related gene signature for overall survival prediction in Asian patients with hepatocellular carcinoma

Purpose Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancers in Asia. Accumulating evidence suggests that ferroptosis is a non-apoptotic form of cell death, and has played an important role in cancer biology. Methods Based on the manually curated ferroptosis-related gene set and TCGA-LIHC dataset of Asian patients, we used DESeq2, Kaplan–Meier analysis, and univariate Cox regression to identify differentially expressed ferroptosis-related genes with significantly prognostic capacity. A risk signature was constructed based on the selected genes for predicting the survival of HCC patients in Asia. The survival prediction accuracy was confirmed by the time-dependent receiver operating characteristic (ROC) curve analysis. Gene set variation analysis (GSVA) was used to explore the functional associations of the signature. Ferroptosis potential index (FPI) and xCell algorithm was applied to quantify ferroptosis and immune cell infiltration, respectively. Two independent datasets from the GEO and the ICGC database were used for external validation. Results The ferroptosis-related signature could accurately predict the survival outcomes of HCC patients in Asian (p value < 0.0001). We showed that the signature was an independent factor and was beneficial in elevating risk stratification of current clinicopathologic features, such as the amount of alpha-fetoprotein (AFP) and residual tumor classification. Functional characterization showed that critical processes in tumorigenesis belonged to the high-risk groups, for example inflammatory response, which may be the main driver of HCC. The high-risk group had higher FPIs and infiltrations of macrophages and T-helper cells than the low-risk group. Furthermore, two independent cohorts confirmed the prognostic value of our signature (AU)

Gelsolin Inhibits the Proliferation of Colon Cancer Cells by Enhancing the Expression of TNFR2/CASP10 as a Death Receptor Pathway.

BACKGROUND: Colon cancer has the second highest incidence rate of digestive system tumors. It relies on surgical treatment, radiotherapy and chemotherapy, and targeted drug therapy. OBJECTIVE: To study the mechanism of GSN in the proliferation of colon cancer cells. MATERIALS AND METHODS: The expression of gelsolin (GSN) was analyzed with the data of colon cancer patients in the TCGA database. SW620 cells were treated by GSN in vitro and the gene expression was detected by immunoblotting and quantitative PCR. RESULTS: The expression of GSN was found significantly low in colon cancer cells and correlated with the prognosis of patients. The SW620 cell line cultured in vitro was treated with exogenous GSN. SW620 can be significantly inhibited above the concentration of 250 µg/ml. The results of immunoblotting and quantitative PCR showed that exogenous GSN can effectively improve the transcription level of death receptor-related pathway genes such as TNFR2 and CASP10. CONCLUSION: This study found that GSN inhibited the proliferation of SW620 cells in vitro by upregulating the expression of death receptor pathway-related proteins.

Mining Polyethylene Glycol-Based Thermosensitive Hydrogel Materials: Preparation and Flame Retardant Properties.

A new type of efficient and anti-extinguishing materials to inhibit coal spontaneous combustion is required because of the current situation of the short activity cycle of existing anti-extinguishing technology. Now, polyethylene glycol (PEG) was used as a water-absorbing monomer to polymerize various substances to prepare an AB-type mining thermosensitive hydrogel that was obviously thermoresponsive. The thermosensitive hydrogel, which is low-cost and stable, can be stored for a long time, and it is prepared by compounding A and B components. The orthogonal experiments determined the optimal ratio of component A, while the controlling variable experiments determined the optimal ratio of component B. The thermal stability and flame-retardant properties of the AB-type thermosensitive hydrogel were analyzed during the process of natural oxidation of coal, and the temperature responsiveness of thermosensitive hydrogels was investigated at different temperatures. The results showed that the optimal ratio of polyethylene glycol:methyl cellulose:sodium carboxymethyl cellulose:guar gum of component A was 6:6:1.2:1.5; and the ratio of bentonite:kaolin:Mg(OH)2 of component B was 2:1:1. When the ratio of component A to component B was 1:2, the AB-type thermosensitive hydrogel shows the best flame retardant properties. When this ratio of gel was applied to coal samples, the weight loss was just 6%, and the reduction of CO was as high as 72.6%. The gel, which was convenient for transportation in mining pipelines, had strong fluidity at low temperatures and rapid temperature response. As the temperature rose, a phase transition occurred gradually, and after the phase transition, a high-viscosity solid substance was formed, whose viscosity was approximately 11 times that of the room temperature. It plugged the pores effectively, and in the high-temperature region, the occurred phase transition gathered to extinguish the fire. It is a new type of high-efficiency anti-extinguishing material with excellent properties.

Sensitive biosensors based on topological insulator Bi2Se3 and peptide.

In this work, we designed a facile and label-free electrochemical biosensor based on intrinsic topological insulator (TI) Bi2Se3 and peptide for the detection of immune checkpoint molecules. With topological protection, Bi2Se3 could have robust surface states with low electronic noise, which was beneficial for the stable and sensitive electron transport between electrode and electrolyte interface. The peptides are easily synthesized and chemically modified, and have good biocompatibility and bioavailability, which is a suitable candidate as the recognition units for immune checkpoint molecules. Therefore, the peptide/Bi2Se3 was developed as a suitable working electrode for the electrochemical biosensor. The basic performance of the designed peptide/Bi2Se3 biosensor was investigated to determine the Anti-HA Tag Antibody and PD-L1 molecules. The linear detection range was from 3.6 × 10-10 mg mL-1 to 3.6 × 10-5 mg mL-1, and the detection limit was 1.07 × 10-11 mg mL-1. Moreover, the biosensor also displayed good selectivity and stability.

Integrated analysis of ferroptosis-related gene signature for overall survival prediction in Asian patients with hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancers in Asia. Accumulating evidence suggests that ferroptosis is a non-apoptotic form of cell death, and has played an important role in cancer biology. METHODS: Based on the manually curated ferroptosis-related gene set and TCGA-LIHC dataset of Asian patients, we used DESeq2, Kaplan-Meier analysis, and univariate Cox regression to identify differentially expressed ferroptosis-related genes with significantly prognostic capacity. A risk signature was constructed based on the selected genes for predicting the survival of HCC patients in Asia. The survival prediction accuracy was confirmed by the time-dependent receiver operating characteristic (ROC) curve analysis. Gene set variation analysis (GSVA) was used to explore the functional associations of the signature. Ferroptosis potential index (FPI) and xCell algorithm was applied to quantify ferroptosis and immune cell infiltration, respectively. Two independent datasets from the GEO and the ICGC database were used for external validation. RESULTS: The ferroptosis-related signature could accurately predict the survival outcomes of HCC patients in Asian (p value < 0.0001). We showed that the signature was an independent factor and was beneficial in elevating risk stratification of current clinicopathologic features, such as the amount of alpha-fetoprotein (AFP) and residual tumor classification. Functional characterization showed that critical processes in tumorigenesis belonged to the high-risk groups, for example inflammatory response, which may be the main driver of HCC. The high-risk group had higher FPIs and infiltrations of macrophages and T-helper cells than the low-risk group. Furthermore, two independent cohorts confirmed the prognostic value of our signature. CONCLUSION: Overall, our results demonstrated potential application of ferroptosis-related genes as independent biomarkers in Asian HCC patients. Targeting ferroptosis may be clinically useful beyond known clinicopathological factors and provide benefit in immunotherapy.

Polystyrene microplastics weaken the predator-induced defenses of Daphnia magna: Evidences from the changes in morphology and behavior.

Polystyrene microplastics are ubiquitous in freshwater ecosystems and have significant impacts on freshwater organisms. Stable interspecific relationships, including the predation and defense relationships between predator and prey, play an extremely important role in maintaining the health of aquatic ecosystems. However, it still remains unknown whether polystyrene microplastics can interfere with predator-induced defenses of prey, especially in behavior change. Therefore, we studied the effects of different particle sizes and concentrations of polystyrene microplastics on the induced defenses related to morphology, reproduction, and behavior of Daphnia magna exposed to the predation risks from a species of zooplanktivorous fish Rhodeus ocellatus. Results showed that polystyrene microplastics weakened the predator-induced defenses of D. magna, including morphology, reproduction, and behavior. Polystyrene microplastics did not affect the beat rate of the second antennae (swimming activity) and thoracic appendage (filter-feeding activity) of D. magna, but R. ocellatus kairomone reduced Daphnia swimming activity. Moreover, in the absence of R. ocellatus predation risks, polystyrene microplastics did not alter the vertical distribution of D. magna in the water column, whereas D. magna exposed to R. ocellatus kairomone stayed deeper in the water; however, when both polystyrene microplastics and fish kairomone were present, D. magna inhabited in shallower water. Furthermore, small-sized microplastics interfered with the inducible behavioral defense of D. magna more strongly than large-sized polystyrene microplastics. Such findings suggested that polystyrene microplastics can weaken the predator-induced defenses of Daphnia, which may increase their risk of predation and alter the population dynamics of zooplankton.

Association between obese phenotypes and risk of carotid artery plaque among chinese male railway drivers.

BACKGROUND: China has the world's highest rail transportation network density, and the prevalence of obesity among railway workers in China is more than twice that of adults in the world. Carotid artery plaque (CAP) is a simple and noninvasive predictor of early atherosclerosis, while the association between different obese phenotypes and CAP risk among Chinese male railway drivers is unclear. METHODS: This cross-sectional study was performed among 8,645 Chinese male railway drivers. Obese phenotypes were assessed based on the obesity status (the body mass index ≥ 28 kg/m2 as obesity vs. < 28 kg/m2 as non-obesity) and metabolic status (metabolically healthy vs. metabolically unhealthy). Metabolically unhealthy was defined as the presence of at least one dysfunction, including elevated blood pressure, elevated fasting blood glucose, elevated triglyceride, and reduced high-density-lipoprotein cholesterol. Four obese phenotypes were defined based on the body mass index and metabolic status, i.e., metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), and metabolically unhealthy non-obesity (MUNO). Multivariable logistic regression was employed to estimate the association between different obese phenotypes and the risk of CAP. Subgroup analysis was performed to examine the variation of the association by age, circadian rhythm disorders, and history of smoking and drinking. RESULTS: The prevalence of CAP among male railway drivers in MHO, MUO, MUNO, and MHNO was 8.75%, 18.67%, 17.82%, and 5.36%, respectively. Compared to those with MHNO, an increased risk for CAP was observed among those with MHO (OR = 2.18, 95% CI: 0.82, 5.10), MUO (OR = 1.78, 95% CI:1.44, 2.21), and MUNO (OR = 2.20, 95% CI: 1.67, 2.89). The subgroup analysis showed that both of the metabolically unhealthy groups (MUNO and MUO) aged < 45 years were prone to a higher risk of CAP (for the MUNO group, OR = 4.27, 95% CI:2.71, 7.10; for the MUO group, OR = 4.00, 95%CI: 2.26, 7.17). CONCLUSION: The obese phenotypes are associated with CAP risk in male railway drivers, especially those with metabolically unhealthy conditions aged < 45 years.