Prenatal immune activation in mice induces long-term alterations in brain mitochondrial function.

Prenatal exposure to infections is a risk factor for neurodevelopmental disorders in offspring, and alterations in mitochondrial function are discussed as a potential underlying factor. Here, using a mouse model of viral-like maternal immune activation (MIA) based on poly(I:C) (POL) treatment at gestational day (GD) 12, we show that adult offspring exhibit behavioral deficits, such as reduced levels of social interaction. In addition, we found increased nicotinamidadenindinucleotid (NADH)- and succinate-linked mitochondrial respiration and maximal electron transfer capacity in the prefrontal cortex (PFC) and in the amygdala (AMY) of males and females. The increase in respiratory capacity resulted from an increase in mitochondrial mass in neurons (as measured by complex IV activity and transcript expression), presumably to compensate for a reduction in mitochondrion-specific respiration. Moreover, in the PFC of control (CON) male offspring a higher excess capacity compared to females was observed, which was significantly reduced in the POL-exposed male offspring, and, along with a higher leak respiration, resulted in a lower mitochondrial coupling efficiency. Transcript expression of the uncoupling proteins (UCP4 and UCP5) showed a reduction in the PFC of POL male mice, suggesting mitochondrial dysfunction. In addition, in the PFC of CON females, a higher expression of the antioxidant enzyme superoxide dismutase (SOD1) was observed, suggesting a higher antioxidant capacity as compared to males. Finally, transcripts analysis of genes involved in mitochondrial biogenesis and dynamics showed reduced expression of fission/fusion transcripts in PFC of POL offspring of both sexes. In conclusion, we show that MIA causes alterations in neuronal mitochondrial function and mass in the PFC and AMY of adult offspring with some effects differing between males and females.

The U-shape Association between Population Agglomeration and Individual Depression: the Role of Dialect Diversity.

Depression is a relevant mental illness affecting hundreds of millions of people worldwide. As urbanization accelerates, agglomeration of populations has altered individual social network distances and life crowding, which in turn affects depressive prevalence. However, the association between depression and population agglomeration (PA) remains controversial. This study aims to explore whether and how PA could influence individual depression. Based on the China Health and Retirement Longitudinal Study (CHARLS) 2018, the empirical results showed that there was a U-shaped association between PA and individual CES-D scores. As PA increases, the risk of depression first decreases and then increases. CES-D was lowest at moderate aggregation. Dialect diversity (DD) was positively related to the incidence of individual depression. The higher the DD, the higher the risk of depression. Meanwhile, DD also played a moderating role in the association between PA and individual depression. Our observations suggest that the optimistic level of agglomeration for individual mental health is within 1500 to 2000 persons per square kilometer.

CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status.

Chaperonin-containing TCP1 (CCT) is a multi-subunit complex, known to participate the correct folding of many proteins. Currently, the mechanism underlying CCT subunits in cancer progression is incompletely understood. Based on data analysis, the expression of CCT subunit 6 A (CCT6A) is found higher than the other subunits of CCT and correlated with an unfavorable prognosis in colon cancer. Here, we find CCT6A silencing suppresses colon cancer proliferation and survival phenotype in vitro and in vivo. CCT6A plays a role in cellular process, including the cell cycle, p53, and apoptosis signaling pathways. Further investigations have shown direct binding between CCT6A and both Wtp53 and Mutp53, and BIRC5 is found to act downstream of CCT6A. The highlight is that CCT6A inhibition significantly reduces BIRC5 expression independent of Wtp53 levels in Wtp53 cells. Conversely, in Mutp53 cells, downregulation of BIRC5 by CCT6A inhibition mainly depends on Mutp53 levels. Additionally, combined CCT6A inhibition and Wtp53 overexpression in Mutp53 cell lines effectively suppresses cell proliferation. It is concluded CCT6A is a potential oncogene that influences BIRC5 through distinct pathways in Wtp53 and Mutp53 cells.

Exploring gingerol glucosides with enhanced anti-inflammatory activity through a newly identified α-glucosidase (ArG) from Agrobacterium radiobacter DSM 30147.

Gingerols are phenolic biomedical compounds found in ginger (Zingiber officinale) whose low aqueous solubility limits their medical application. To improve their solubility and produce novel glucosides, an α-glucosidase (glycoside hydrolase) from Agrobacterium radiobacter DSM 30147 (ArG) was subcloned, expressed, purified, and then confirmed to have additional α-glycosyltransferase activity. After optimization, the ArG could glycosylate gingerols into three mono-glucosides based on the length of their acyl side chains. Compound 1 yielded 63.0 %, compound 2 yielded 26.9 %, and compound 3 yielded 4.37 %. The production yield of the gingerol glucosides optimally increased in 50 mM phosphate buffer (pH 6) with 50 % (w/v) maltose and 1000 mM Li+ at 40 °C for an 24-h incubation. The structures of purified compound 1 and compound 2 were determined as 6-gingerol-5-O-α-glucoside (1) and novel 8-gingerol-5-O-α-glucoside (2), respectively, using nucleic magnetic resonance and mass spectral analyses. The aqueous solubility of the gingerol glucosides was greatly improved. Further assays showed that, unusually, 6-gingerol-5-O-α-glucoside had 10-fold higher anti-inflammatory activity (IC50 value of 15.3 ± 0.5 µM) than 6-gingerol, while the novel 8-gingerol-5-O-α-glucoside retained 42.7 % activity (IC50 value of 106 ± 4 µM) compared with 8-gingerol. The new α-glucosidase (ArG) was confirmed to have acidic α-glycosyltransferase activity and could be applied in the production of α-glycosyl derivatives. The 6-gingerol-5-O-α-glucoside can be applied as a clinical drug for anti-inflammatory activity.

Autosomal Recessive Hypophosphatemic Rickets Type 2 Associated with a Novel ENPP1 Variant in a Taiwanese Girl.

Autosomal recessive hypophosphatemic rickets (HR) type 2 (ARHR2) is a rare form of HR caused by variant of the gene encoding ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Our patient presented with a history of unsteady gait and progressively bowing legs that had commenced at the age of 1 year. Laboratory tests revealed an elevated level of fibroblast growth factor 23 (FGF23), hypophosphatemia, and a high urine phosphate level. Radiography revealed the typical features of rickets. Next-generation sequencing identified a previously reported c.783C>G (p.Tyr261Ter) and a novel c.1092-42A>G variant in the ENPP1 gene. The patient was prescribed oral phosphates and active vitamin D and underwent guided growth of both distal femora and proximal tibiae commencing at the age of 3 years. No evidence of generalized arterial calcification was apparent during follow-up, and growth rate was satisfactory.

Dual Roles of the Photooxidation of Organic Amines for Enhanced Triplet-Triplet Annihilation Upconversion in Nanoparticles.

Oxygen-mediated triplet-triplet annihilation upconversion (TTA-UC) quenching limits the application of such organic upconversion materials. Here, we report that the photooxidation of organic amines is an effective and versatile strategy to suppress oxygen-mediated upconversion quenching in both organic solvents and aqueous solutions. The strategy is based on the dual role of organic amines in photooxidation, i.e., as singlet oxygen scavengers and electron donors. Under photoexcitation, the photosensitizer sensitizes oxygen to produce singlet oxygen for the oxidation of alkylamine, reducing the oxygen concentration. However, photoinduced electron transfer among photosensitizers, organic amines, and oxygen leads to the production of superoxide anions that suppress TTA-UC. To observe oxygen-tolerating TTA-UC, we find that alkyl secondary amines can balance the production of singlet oxygen and superoxide anions. We then utilize polyethyleneimine (PEI) to synthesize amphiphilic polymers to encapsulate TTA-UC pairs for the formation of water-dispersible, ultrasmall, and multicolor-emitting TTA-UC nanoparticles.

Establishment of a Mitochondrial Metabolism-Related Diagnostic Model in Schizophrenia Based on LASSO Algorithm.

OBJECTIVE: Schizophrenia is a common mental disorder, and mitochondrial function represents a potential therapeutic target for psychiatric diseases. The role of mitochondrial metabolism-related genes (MRGs) in the diagnosis of schizophrenia remains unknown. This study aimed to identify candidate genes that may influence the diagnosis and treatment of schizophrenia based on MRGs. METHODS: Three schizophrenia datasets were obtained from the Gene Expression Omnibus database. MRGs were collected from relevant literature. The differentially expressed genes between normal samples and schizophrenia samples were screened using the limma package. Venn analysis was performed to identify differentially expressed MRGs (DEMRGs) in schizophrenia. Based on the STRING database, hub genes in DEMRGs were identified using the MCODE algorithm in Cytoscape. A diagnostic model containing hub genes was constructed using LASSO regression and logistic regression analysis. The relationship between hub genes and drug sensitivity was explored using the DSigDB database. An interaction network between miRNA-transcription factor (TF)-hub genes was created using the Network-Analyst website. RESULTS: A total of 1,234 MRGs, 172 DEMRGs, and 6 hub genes with good diagnostic performance were identified. Ten potential candidate drugs (rifampicin, fulvestrant, pentadecafluorooctanoic acid, etc.) were selected. Thirty-four miRNAs targeting genes in the diagnostic model (ANGPTL4, CPT2, GLUD1, MED1, and MED20), as well as 137 TFs, were identified. CONCLUSION: Six potential candidate genes showed promising diagnostic significance. rifampicin, fulvestrant, and pentadecafluorooctanoic acid were potential drugs for future research in the treatment of schizophrenia. These findings provided valuable evidence for the understanding of schizophrenia pathogenesis, diagnosis, and drug treatment.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Emergency room visits (ERVs) among occupational groups associated with ambient conditions in Taiwan.

OBJECTIVE: This population-based study explored emergency room visits (ERVs) from all-causes, circulatory and respiratory diseases among different occupational groups in Taiwan associated with ambient average temperature. METHOD: Daily area-age-sex specific ERVs records were obtained from the Taiwan's Ministry of Health and Welfare from 2009 to 2018. Distributed lag-nonlinear model (DLNM) was used to estimate the exposure-response relationships between daily average temperature and ERVs for all-causes, circulatory and respiratory diseases by occupational groups. Random-effects meta-analysis was used to pool the overall cumulative relative risk (RR) and 95% confidence interval (CI). RESULTS: The exposure-response curves showed ERVs of all-cause and respiratory diseases increased with rising temperature across all occupational groups. These effects were consistently stronger among younger (20-64 years old) and outdoor workers. In contrast, ERVs risk from circulatory diseases increased significantly during cold snaps, with a substantially higher risk for female workers. Interestingly, female workers, regardless of indoor or outdoor work, consistently showed a higher risk of respiratory ERVs during hot weather compared to males. Younger workers (20-64 years old) exhibited a higher risk of ERVs, likely due to job profiles with greater exposure to extreme temperatures. Notably, the highest risk of all-causes ERVs was observed in outdoor male laborers (union members), followed by farmers and private employees, with the lowest risk among indoor workers. Conversely, female indoor workers and female farmers faced the highest risk of respiratory ERVs. Again, female farmers with consistent outdoor exposure had the highest risk of circulatory ERVs during cold conditions. CONCLUSION: Our findings highlighted the complexity of temperature-related health risks associated with different occupational contexts. The population-level insights into vulnerable occupational groups could provide valuable comprehension for policymakers and healthcare practitioners.

Ultrafast Unidirectional On-Chip Heat Transfer.

Effective and rapid heat transfer is critical to improving electronic components' performance and operational stability, particularly for highly integrated and miniaturized devices in complex scenarios. However, current thermal manipulation approaches, including the recent advancement in thermal metamaterials, cannot realize fast and unidirectional heat flow control. In addition, any defects in thermal conductive materials cause a significant decrease in thermal conductivity, severely degrading heat transfer performance. Here, the utilization of silicon-based valley photonic crystals (VPCs) is proposed and numerically demonstrated to facilitate ultrafast, unidirectional heat transfer through thermal radiation on a microscale. Utilizing the infrared wavelength region, the approach achieves a significant thermal rectification effect, ensuring continuous heat flow along designed paths with high transmission efficiency. Remarkably, the process is unaffected by temperature gradients due to the unidirectional property, maintaining transmission directionality. Furthermore, the VPCs' inherent robustness affords defect-immune heat transfer, overcoming the limitations of traditional conduction methods that inevitably cause device heating, performance degradation, and energy waste. The design is fully CMOS compatible, thus will find broad applications, particularly for integrated optoelectronic devices.

Biomarkers Screening and Mechanisms Analysis of the Restraint Stress-Induced Myocardial Injury in Hyperlipidemia ApoE-/- Mice.

OBJECTIVES: To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/- mice. METHODS: The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers. RESULTS: Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model. CONCLUSIONS: Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death (SCD) caused by hyperlipidemia combined with the restraint stress.

Triclosan inhibits testosterone biosynthesis in adult rats via inducing m6A methylation-mediated autophagy.

Triclosan is a potent antibacterial compound widely used in everyday products. Whether triclosan affects Leydig cell function in adult male rats remains unknown. In this study, 0, 50, 100, or 200 mg/kg/day triclosan was gavaged to Sprague-Dawley male rats from 56 to 63 days postpartum. Triclosan significantly reduced serum testosterone levels at ≥ 50 mg/kg/day via downregulating the expression of Leydig cell gene Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3 and regulatory transcription factor Nr3c2 at 100-200 mg/kg. Further analysis showed that triclosan markedly increased autophagy as shown by increasing LC3II and BECN1 and decreasing SQSTM1. The mRNA m6A modification analysis revealed that triclosan significantly downregulated Fto expression at 200 mg/kg while upregulating Ythdf1 expression at 100 and 200 mg/kg, leading to methylation of Becn1 mRNA as shown by MeRIP assay. Triclosan significantly inhibited testosterone output in rat R2C Leydig cells at ≥ 5 µM via downregulating Fto and upregulating Ythdf1. SiRNA Ythdf1 knockdown can reverse triclosan-mediated mitophagy in R2C cells, thereby reversing the reduction of testosterone output. In summary, triclosan caused Becn1 m6A methylation by downregulating Fto and upregulating Ythdf1, which accelerated Becn1 translation, thus leading to the occurrence of autophagy and the decrease of testosterone biosynthesis.

Anthropogenic events and responses to environmental stress are shaping the genomes of Ethiopian indigenous goats.

Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We analyzed 57 Ethiopian indigenous domestic goat genomes alongside 67 equivalents of east, west, and north-west African, European, South Asian, Middle East, and wild Bezoar goats. Cluster, ADMIXTURE (K = 4) and phylogenetic analysis revealed four genetic groups comprising African, European, South Asian, and wild Bezoar goats. The Middle Eastern goats had an admixed genome of these four genetic groups. At K = 5, the West African Dwarf and Moroccan goats were separated from East African goats demonstrating a likely historical legacy of goat arrival and dispersal into Africa via the coastal Mediterranean Sea and the Horn of Africa. FST, XP-EHH, and Hp analysis revealed signatures of selection in Ethiopian goats overlaying genes for thermo-sensitivity, oxidative stress response, high-altitude hypoxic adaptation, reproductive fitness, pathogen defence, immunity, pigmentation, DNA repair, modulation of renal function and integrated fluid and electrolyte homeostasis. Notable examples include TRPV1 (a nociception gene); PTPMT1 (a critical hypoxia survival gene); RETREG (a regulator of reticulophagy during starvation), and WNK4 (a molecular switch for osmoregulation). These results suggest that human-mediated translocations and adaptation to contrasting environments are shaping indigenous African goat genomes.

Heterostructure g-C3N4/Bi2MoO6 PVDF nanofiber composite membrane for the photodegradation of steroid hormone micropollutants.

Photocatalytic membrane reactors (PMRs) are a promising technology for micropollutant removal. Sunlight utilization and catalyst surface sites limit photodegradation. A poly(vinylidene fluoride) (PVDF) nanofiber composite membrane (NCM) with immobilized visible-light-responsive g-C3N4/Bi2MoO6 (BMCN) were developed. Photodegradation of steroid hormones with the PVDF-BMCN NCM was investigated with varying catalyst properties, operating conditions, and relevant solution chemistry under solar irradiation. Increasing CN ratio (0-65 %) enhanced estradiol (E2) degradation from 20 ± 10 to 75 ± 7 % due to improved sunlight utilization and photon lifetime. PVDF nanofibers reduced self-aggregation of catalysts. Hydraulic residence time and light intensity enhanced the photodegradation. With the increasing pH value, the E2 removal decreased from 84 ± 4 to 67 ± 7 % owing to electrical repulsion and thus reduced adsorption between catalysts and E2. A removal of 96 % can be attained at environmentally relevant feed concentration (100 ng.L-1) with a flux of 60 L.m-2.h-1, irradiance of 100 mW.cm-2, and 1 mg.cm-2 BMCN65 loading. This confirmed that heterojunction photocatalysts can enhance micropollutants degradation in PMRs.

A distinct dimer configuration of a diatom Get3 forming a tetrameric complex with its tail-anchored membrane cargo.

BACKGROUND: Most tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown. RESULTS: Here, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition. CONCLUSIONS: Our study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom's cell membrane.

High-frequency monitoring during rainstorm events reveals nitrogen sources and transport in a rural catchment.

Rural areas lacking essential sewage treatment facilities and collection systems often experience eutrophication due to elevated nutrient loads. Understanding nitrogen (N) sources and transport mechanisms in rural catchments is crucial for improving water quality and mitigating downstream export loads, particularly during storm events. To further elucidate the sources, pathways, and transport mechanisms of N from a rural catchment with intensive agricultural activities during storm events, we conducted an analysis of 21 events through continuous sampling over two rainy seasons in a small rural catchment from the lower reaches of the Yangtze River. The results revealed that ammonia-N (NH4+-N) and nitrate-N (NO3--N) exhibited distinct behaviors during rainstorm events, with NO3--N accounting for the primary nitrogen loss, its load being approximately forty times greater than that of NH4+-N. Through examinations of the concentration-discharge (c-Q) relationships, the findings revealed that, particularly in prolonged rainstorms, NH4+-N exhibited source limited pattern (b = -0.13, P < 0.01), while NO3--N displayed transport limited pattern (b = -0.21, P < 0.01). The figure-eight hysteresis pattern was prevalent for both NH4+-N and NO3--N (38.1% and 52.0%, respectively), arising from intricate interactions among diverse sources and pathways. For NO3--N, the hysteresis pattern shifted from clockwise under short-duration rainstorms to counter-clockwise under long-duration rainstorms, whereas hysteresis remained consistently clockwise for NH4+-N. The hysteresis analysis further suggests that the duration of rainstorms modifies hydrological connectivity, thereby influencing the transport processes of N. These insights provide valuable information for the development of targeted management strategies to reduce storm nutrient export in rural catchments.

Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study.

BACKGROUND: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance. METHODS: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC. RESULTS: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC. CONCLUSIONS: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.

Enhancing safety in conditionally automated driving: Can more takeover request visual information make a difference in hazard scenarios with varied hazard visibility?

Autonomous driving technology has the potential to significantly reduce the number of traffic accidents. However, before achieving full automation, drivers still need to take control of the vehicle in complex and diverse scenarios that the autonomous driving system cannot handle. Therefore, appropriate takeover request (TOR) designs are necessary to enhance takeover performance and driving safety. This study focuses on takeover tasks in hazard scenarios with varied hazard visibility, which can be categorized as overt hazards and covert hazards. Through ergonomic experiments, the impact of TOR interface visual information, including takeover warning, hazard direction, and time to collision, on takeover performance is investigated, and specific analyses are conducted using eye-tracking data. The following conclusions are drawn from the experiments: (1) The visibility of hazards significantly affects takeover performance. (2) Providing more TOR visual information in hazards with different visibility has varying effects on drivers' visual attention allocation but can improve takeover performance. (3) More TOR visual information helps reduce takeover workload and increase human-machine trust. Based on these findings, this paper proposes the following TOR visual interface design strategies: (1) In overt hazard scenarios, only takeover warning is necessary, as additional visual information may distract drivers' attention. (2) In covert hazard scenarios, the TOR visual interface should better assist drivers in understanding the current hazard situation by providing information on hazard direction and time to collision to enhance takeover performance.

Limitations and Innovative Application Methods of Surfactants for Solubilization of Poorly Water-Soluble Drugs.

Poor solubility of drugs leads to poor bioavailability and therapeutic efficiency. A large proportion of drugs that are not developed and marketed for use by patients are due to their extremely low solubility. Therefore, improving the solubility of poorly water-soluble drugs is one of the most important aspects of the field of drug research. With the continuous development of more and more formulation techniques and excipient applications, the solubility of poorly water-soluble drugs can be improved to a certain extent to obtain better pharmacokinetics and pharmacodynamics, including pH microenvironment regulation technology, inclusion complex, solid dispersion, nanotechnology, and application of surfactants. However, the most widely used among them is the application of surfactants. This technique can reduce the surface tension, improve wettability, and have a remarkable solubilizing ability after forming micelles. However, surfactants have also been found to possess certain limitations in solubilization. In this review, the factors affecting the solubilization of surfactants and limiting their application have been summarized from several aspects. These factors include drugs, additives, and media. Some ideas to solve these application limitations have also been put forward, which can lay a foundation for the wider application of surfactants in the future.