Discovery of an immunosuppressive functional metabolite from the insect-derived endophytic Aspergillus taichungensis SMU01.

Three p-terphenyl metabolites (1-3), three indole-diterpenoids (4-6), an herbicide sesquiterpene (7), a flavonoid (8), and five other small molecules containing nitrogen (9-13) were isolated from the medicinal insect (Periplaneta americana)-derived endophytic Aspergillus taichungensis SMU01. Their chemical structures were elucidated on the basis of spectroscopic data and quantum chemical computational methods. Biological activity of these isolates in the differentiation of mouse CD4+ T cell subsets was evaluated. Importantly, metabolites 2 targeting JAK-STAT signaling pathway could hold potential benefits in maintaining peripheral immune homeostasis and alleviating the progression of autoimmune diseases.

The effects of ambient temperature on road traffic injuries in Jinan city: a time-stratified case-crossover study based on distributed lag nonlinear model.

Objectives: The impact of climate change, especially extreme temperatures, on health outcomes has become a global public health concern. Most previous studies focused on the impact of disease incidence or mortality, whereas much less has been done on road traffic injuries (RTIs). This study aimed to explore the effects of ambient temperature, particularly extreme temperature, on road traffic deaths in Jinan city. Methods: Daily data on road traffic deaths and meteorological factors were collected among all residents in Jinan city during 2011-2020. We used a time-stratified case-crossover design with distributed lag nonlinear model to evaluate the association between daily mean temperature, especially extreme temperature and road traffic deaths, and its variation in different subgroups of transportation mode, adjusting for meteorological confounders. Results: A total of 9,794 road traffic deaths were collected in our study. The results showed that extreme temperatures were associated with increased risks of deaths from road traffic injuries and four main subtypes of transportation mode, including walking, Bicycle, Motorcycle and Motor vehicle (except motorcycles), with obviously lag effects. Meanwhile, the negative effects of extreme high temperatures were significantly higher than those of extreme low temperatures. Under low-temperature exposure, the highest cumulative lag effect of 1.355 (95% CI, 1.054, 1.742) for pedal cyclists when cumulated over lag 0 to 6 day, and those for pedestrians, motorcycles and motor vehicle occupants all persisted until 14 days, with ORs of 1.227 (95% CI, 1.102, 1.367), 1.453 (95% CI, 1.214, 1.740) and 1.202 (95% CI, 1.005, 1.438), respectively. Under high-temperature exposure, the highest cumulative lag effect of 3.106 (95% CI, 1.646, 5.861) for motorcycle occupants when cumulated over lag 0 to 12 day, and those for pedestrian, pedal cyclists, and motor vehicle accidents all peaked when persisted until 14 days, with OR values of 1.638 (95% CI, 1.281, 2.094), 2.603 (95% CI, 1.695, 3.997) and 1.603 (95% CI, 1.066, 2.411), respectively. Conclusion: This study provides evidence that ambient temperature is significantly associated with the risk of road traffic injuries accompanied by obvious lag effect, and the associations differ by the mode of transportation. Our findings help to promote a more comprehensive understanding of the relationship between temperature and road traffic injuries, which can be used to establish appropriate public health policies and targeted interventions.

BrBCAT1 mutation resulted in deficiency of epicuticular wax crystal in Chinese cabbage.

KEY MESSAGE: BrBCAT1 encoding a branched-chain amino acid aminotransferase was responsible for the glossy trait, which was verified by allelic mutants in Chinese cabbage. The glossy characteristic, thanks to the epicuticular wax crystal deficiency, is an excellent commodity character for leafy vegetables. Herein, two allelic glossy green mutants, wdm11 and wdm12, were isolated from an ethyl methane sulfonate (EMS)-mutagenized population of Chinese cabbage, and the mutant phenotype was recessive inherited. Cryo-SEM detected that epicuticular wax crystal in the mutant leaves was virtually absent. MutMap and Kompetitive allele-specific PCR analyses demonstrated that BraA06g006950.3C (BrBCAT1), homologous to AtBCAT1, encoding a branched-chain amino acid aminotransferase was the candidate gene. A SNP (G to A) on the fourth exon of BrBCAT1 in wdm11 caused the 233rd amino acid to change from glycine (G) to aspartic acid (D). A SNP (G to A) on the second exon of BrBCAT1 in wdm12 led to the 112th amino acid change from glycine (G) to arginine (R). Both of the allelic mutants had genetic structural variation in the candidate gene, which indicated that the mutant phenotype was triggered by the BrBCAT1 mutation. The expression levels of BrBCAT1 and genes related to fatty acid chain extension were decreased significantly in the mutant compared to the wild-type, which might result in epicuticular wax crystal deficiency in the mutants. Our findings proved that the mutation of BrBCAT1 induced the glossy phenotype and provided a valuable gene resource for commodity character improvement in Chinese cabbage.

Anisotropic optical property of ferroelectric Bi2O2X (X=S,Se,Te) monolayer and strain engineering.

Based on the first-principles calculations, ferroelectric Bi2O2X (X=S, Se, Te) monolayers with unequivalent in-plane lattice constants are confirmed to be the ground state, which is consistent with the experiment result (Nano Lett. 19, 5703(2019)), and the anisotropic optical property is firstly investigated. We find that the polarizations of Bi2O2X monolayers points along the direction of a-axis, and Bi2O2T e monolayer process the largest polarization. Furthermore, both the biaxial and uniaxial strains are favor for the enhancement of polarization of Bi2O2X monolayers. It should be mentioned that the type of band gap will convert from indirect to direct for Bi2O2T e monolayer when the a-axial tensile strain is larger than 2%. At last, the optical absorption coefficient for Bi2O2X monolayers are calculated, and we obtain that Bi2O2Te monolayer has the strongest optical absorption within the range of visible light, the anisotropy and possible strain engineering to improve the optical absorption are discussed in detail. Our findings are significant in fields of optoelectronics and photovoltaics. .

Immunization with a low dose of zymosan A confers resistance to depression-like behavior and neuroinflammatory responses in chronically stressed mice.

Stimulation of the innate immune system prior to stress exposure is a possible strategy to prevent depression under stressful conditions. Based on the innate immune system stimulating activities of zymosan A, we hypothesize that zymosan A may prevent the development of chronic stress-induced depression-like behavior. Our results showed that a single injection of zymosan A 1 day before stress exposure at a dose of 2 or 4 mg/kg, but not at a dose of 1 mg/kg, prevented the development of depression-like behaviors in mice treated with chronic social defeat stress (CSDS). The prophylactic effect of a single zymosan A injection (2 mg/kg) on CSDS-induced depression-like behaviors disappeared when the time interval between zymosan A and stress exposure was extended from 1 day or 5 days to 10 days, which was rescued by a second zymosan A injection 10 days after the first zymosan A injection and 4 days (4×, once daily) of zymosan A injections 10 days before stress exposure. Further analysis showed that a single zymosan A injection (2 mg/kg) 1 day before stress exposure could prevent the CSDS-induced increase in pro-inflammatory cytokines in the hippocampus and prefrontal cortex. Inhibition of the innate immune system by pretreatment with minocycline (40 mg/kg) abolished the preventive effect of zymosan A on CSDS-induced depression-like behaviors and CSDS-induced increase in pro-inflammatory cytokines in the brain. These results suggest that activation of the innate immune system triggered by zymosan A prevents the depression-like behaviors and neuroinflammatory responses in the brain induced by chronic stress.

[Facial nerve protection in surgery for rare tumors of the internal auditory canal].

Objective:To explore strategies for preserving facial nerve function during surgeries for rare tumors of the internal auditory canal. Methods:A total of 235 cases of internal auditory canal tumors treated between 2010 and 2023 were included, encompassing vestibular schwannomas, cavernous hemangiomas, meningiomas, and other rare tumors. Various data, including clinical presentations, imaging classifications, and treatment processes, were meticulously analyzed to delineate the characteristics of rare tumors and assess pre-and postoperative facial nerve function. Results:Among all internal auditory canal tumors, vestibular schwannomas accounted for 91.9%. In rare tumors, facial nerve schwannomas constituted 5.3%, cavernous hemangiomas 26.3%, meningiomas 15.8%, and arterial aneurysms 10.5%. Significantly, patients with cavernous hemangiomas displayed pronounced invasion of the facial nerve by the tumor, in contrast to other tumor types where clear boundaries with the facial nerve were maintained. During surgery, individualized approaches and strategies for facial nerve protection were implemented for different tumor types, involving intraoperative dissection, tumor excision, and facial nerve reconstruction. Conclusion:Preservation of the facial nerve is crucial in the surgical management of rare tumors of the internal auditory canal. Accurate preoperative diagnosis, appropriate timing of surgery, selective surgical approaches, and meticulous intraoperative techniques can maximize the protection of facial nerve function. Personalized treatment plans and strategies for facial nerve functional reconstruction are anticipated to enhance surgical success rates, reduce the risk of postoperative facial nerve dysfunction, and ultimately improve the quality of life for patients.

The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia.

The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML. In addition, we revealed that the regulation of CBP-DOT1L axis in MLLr-AML by ATM was independent of DNA damage activation. Our findings provide insight into the signalling pathways involoved in MLLr-AML and broaden the understanding of the role of DDR enzymes beyond processing DNA damage, as well as identigying them as potent cancer targets.

Analysis of the efficacy of separation surgery for severe neurological compression in multiple myeloma: a retrospective analysis of 35 cases.

PURPOSE: To investigate the effectiveness and safety of separation surgery for Epidural Spinal Cord Compression (ESCC) graded ≥ 2 in patients with Multiple Myeloma (MM), analyze factors influencing surgical outcomes, and develop a preliminary treatment decision framework for these patients. METHODS: A retrospective analysis was conducted on clinical data from 35 MM patients who underwent separation surgery for ESCC graded ≥ 2 between 2013 and 2018. Patient data, including baseline information, surgical details, complications, and pre-operative as well as one-month post-operative efficacy evaluation indicators were recorded. Statistical analysis was performed on pre-operative and post-operative efficacy indicators to determine if there were significant improvements (p < 0.05). Ordered logistic regression was utilized to assess factors associated with an unfavorable post-operative quality of life outcome. RESULTS: Compared to pre-operative values, at one-month post-surgery, patients showed significant improvements in Frankel Score Classification (4 vs 5, p < 0.05), Karnofsky Performance Score (30 vs 70, p < 0.05), and Visual Analogue Scale (8 vs 3, p < 0.05). Complications occurred in 7 cases (20%). The number of segments with ESCC (OR = 0.171, p < 0.05) and pre-operative chemotherapy (OR = 5.202, p = 0.05) were identified as independent factors influencing patient outcomes. Patients with more than two vertebral segments with ESCC exhibited significantly worse post-operative conditions. CONCLUSIONS: Separation surgery effectively alleviates pain, improves neurological function, and enhances the quality of life in patients with ESCC graded ≥ 2 due to MM.

Targeting aging and age-related diseases with vaccines.

Aging is a major risk factor for numerous chronic diseases. Vaccination offers a promising strategy to combat these age-related diseases by targeting specific antigens and inducing immune responses. Here, we provide a comprehensive overview of recent advances in vaccine-based interventions targeting these diseases, including Alzheimer's disease, type II diabetes, hypertension, abdominal aortic aneurysm, atherosclerosis, osteoarthritis, fibrosis and cancer, summarizing current approaches for identifying disease-associated antigens and inducing immune responses against these targets. Further, we reflect on the recent development of vaccines targeting senescent cells, as a strategy for more broadly targeting underlying causes of aging and associated pathologies. In addition to highlighting recent progress in these areas, we discuss important next steps to advance the therapeutic potential of these vaccines, including improving and robustly demonstrating efficacy in human clinical trials, as well as rigorously evaluating the safety and long-term effects of these vaccine strategies.

Effect of table tennis balls with different materials and structures on the hardness and elasticity.

The new material introduced by the ITTF in 2014 for table tennis balls has attracted significant attention from players and coaches. Changes in both material selection and production procedures are likely to have affected the static performance of the ball. However, the raw data regarding the elasticity and hardness of these new material balls, encompassing various brands and structures, often lacks practical information crucial for players' rapid adaptation and daily training. The static properties tested in this study were provided by the ITTF, covering both hardness and elasticity. Based on computed variables, this study revealed that the hardness of seam balls at the equator was not consistently higher than that at the pole. Additionally, the study confirmed that the hardness and bounce height of new material balls exceeded those of celluloid. Furthermore, correlation analysis was conducted to examine the relationship between these two properties, revealing a significant correlation between the hardness of seamless balls and their elasticity. This study provides an analysis of the static performance of various types of new material balls, aiding players and coaches in better understanding official event balls and offering a theoretical foundation for the formulation of diverse training and game strategies.

Emission factors and source profiles of volatile organic compounds from the automobile manufacturing industry.

Controlling volatile organic compounds (VOCs) emitted from the automobile manufacturing industry requires establishing VOCs emission factors (EFs) and source profiles refinedly. In this study, 41 samples involved 32 VOCs discharge links were collected from three factories. The EFs and VOCs source profiles were estimated by the material balance method and weighted average method, respectively. The ozone formation potential (OFP) of the 110 VOCs species were calculated by the maximum incremental reactivity (MIR). According to estimations, the ranges of EFs were 0.23-1.66 kg VOCs/SUV car and 2.14-14.86 g VOCs/m2 painted area. EFs of six materials were firstly estimated, which are electrophoretic primer (152.31 ± 97.39 g VOCs/SUV car, 0.97 ± 0.38 g VOCs/m2 painted area), sealant (48.39 ± 26.20 g VOCs/SUV car, 0.46 ± 0.25 g VOCs/m2 painted area), floating coat (87.40 ± 75.63 g VOCs/SUV car, 0.86 ± 0.74 g VOCs/m2 painted area), colored paint (127.24 ± 168.24 g VOCs/SUV car, 1.25 ± 1.66 g VOCs/m2 painted area), varnish (205.46 ± 218.14 g VOCs/SUV car, 2.01 ± 2.15 g VOCs/m2 painted area), and cleaning solvent (328.54 ± 404.94 g VOCs/SUV car, 3.23 ± 3.98 g VOCs/m2 painted area). OVOCs (37.40-51.60 %) and aromatics (36.40-37.00 %) were the dominant components. n-Butyl acetate, 1,2,4-trimethylbenzene, undecane, n-hexanal, acetone, 1,2,3-trimethylbenzene, 1,3,5 -trimethylbenzene, m/p/o-xylene, 3-ethylbenzene, and 4-ethylbenzene were the major VOCs species, accounting for 68 % of total VOCs in the automobile manufacturing industry. Considering the OFP values of species, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene, 1,2,3-trimethylbenzene, m/p-xylene, acetaldehyde, methyl ethyl ketone are the key active species that should be prioritized for control.

Research on the slip deformation characteristics and improvement measures of concrete-faced rockfill dams on dam foundations with large dip angles.

The pumped storage power station (PSPS) is an important measure to achieve the strategic goal of "dual carbon". As one of the preferred types for the upper reservoir dams of PSPSs, the concrete-faced rockfill dam (CFRD) often has a dam foundation on a steep transverse slop and is prone to produce slip deformation along the slope, resulting in poor anti-sliding stability of the dam slope. It is dangerous for the operation safety of PSPSs. Therefore, the slip deformation of CFRDs on dam foundations with large dip angles is investigated. The mechanism for the initiation of slip deformation is revealed. The design measures of physical mechanic and geometric structure are proposed to reduce slip deformation. The results show that the larger sliding forces and smaller anti-sliding forces are the fundamental reasons that CFRDs on dam foundations with large dip angles are prone to produce slip deformation. The larger the dip angle of the dam foundation, the larger the slip deformation of the dam body and face slab, and the smaller the safety factor of the dam slope. When the dip angle of the dam foundation is greater than 15°, the safety factor of the dam slope is less than the minimum value of 1.5 required by codes. The addition of pressure slopes can effectively reduce the slip deformation of the dam body or face slab and significantly improve the anti-sliding stability of the dam slope. When the height or width of the pressure slope platform is greater and the cohesion or internal friction angle of the pressure slope is larger, the slip deformations of the dam body and face slab are smaller, and the safety factor of the dam slope is greater. It is recommended that the height and width of the pressure slope platform be 1/2 times the maximum height of the main dam, and the density (cohesion and internal friction angle) of the pressure slope be equivalent to that of the main dam's rockfill material. The research results can provide theoretical and technical support for the design and construction of CFRDs for the upper reservoir of PSPSs.

Causes and global, regional, and national burdens of traumatic brain injury from 1990 to 2019.

PURPOSE: Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI. METHODS: A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region (n = 21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. RESULTS: In 2019, there were 27.16 million (95% uncertainty intervals (UI): 23.36 - 31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298-401) and 599 per 100,000 population (95% UI: 573-627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% - -0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% - 0.06%). TBI caused 7.08 million (95% UI: 5.00 - 9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 - 117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. CONCLUSIONS: The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

Case report and literature review of rezvilutamide in the treatment of hormone-sensitive prostate cancer.

Background: Prostate cancer represents a major health concern worldwide, with the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and locally advanced prostate cancer posing a particular challenge. Rezvilutamide, a new androgen receptor antagonist from China, has shown early promise; however, its real-world effectiveness and safety profile require further evidence. This case series evaluates the preliminary clinical outcomes of rezvilutamide in combination with androgen deprivation therapy (ADT), focusing on PSA response and radiological findings across various stages of prostate cancer in four patients. Case description: Case 1 details a 68-year-old male with low-volume mHSPC who exhibited a positive therapeutic response, demonstrated by decreasing PSA levels and improved radiographic results, despite experiencing mild side effects related to the drug. Case 2 describes a 71-year-old male with high-volume mHSPC who had a favorable outcome, with no significant changes in tumor size or metastatic spread and no negative reactions to the drug. Case 3 involves a 55-year-old male with locally advanced prostate cancer, who saw a reduction in PSA levels and a small decrease in tumor volume, yet with ongoing bladder involvement. Genetic testing showed no significant mutations. Case 4 presents a 74-year-old male with extensive metastatic disease who initially responded to the treatment but later exhibited disease advancement and an ATM gene mutation, signaling a shift to metastatic castration-resistant prostate cancer (mCRPC). This finding underscores the crucial role of genetic testing in directing future treatment, with therapies such as olaparib or chemotherapy being advised. Conclusions: Rezvilutamide has shown a potential benefit in the management of mHSPC and locally advanced prostate cancer, generally with a mild safety profile. Initial positive responses, particularly in PSA decline and radiographic progression, are promising. Nevertheless, the varying responses, notably concerning genetic mutations, highlight the necessity for tailored treatment approaches. Due to the small cohort and brief follow-up period, more extensive research with larger populations and prolonged monitoring is essential to conclusively determine the benefits and safety of rezvilutamide. The utilization of genetic insights is key to refining treatment decisions and enhancing outcomes for patients with advanced prostate cancer.

Identifying gray matter alterations in Cushing's disease using machine learning: An interpretable approach.

BACKGROUND: Cushing's Disease (CD) is a rare clinical syndrome characterized by excessive secretion of adrenocorticotrophic hormone, leading to significant functional and structural brain alterations as observed in Magnetic Resonance Imaging (MRI). While traditional statistical analysis has been widely employed to investigate these MRI changes in CD, it has lacked the ability to predict individual-level outcomes. PURPOSE: To address this problem, this paper has proposed an interpretable machine learning (ML) framework, including model-level assessment, feature-level assessment, and biology-level assessment to ensure a comprehensive analysis based on structural MRI of CD. METHODS: The ML framework has effectively identified the changes in brain regions in the stage of model-level assessment, verified the effectiveness of these altered brain regions to predict CD from normal controls in the stage of feature-level assessment, and carried out a correlation analysis between altered brain regions and clinical symptoms in the stage of biology-level assessment. RESULTS: The experimental results of this study have demonstrated that the Insula, Fusiform gyrus, Superior frontal gyrus, Precuneus, and the opercular portion of the Inferior frontal gyrus of CD showed significant alterations in brain regions. Furthermore, our study has revealed significant correlations between clinical symptoms and the frontotemporal lobes, insulin, and olfactory cortex, which also have been confirmed by previous studies. CONCLUSIONS: The ML framework proposed in this study exhibits exceptional potential in uncovering the intricate pathophysiological mechanisms underlying CD, with potential applicability in diagnosing other diseases.

Cortical specialization associated with native speech category acquisition in early infancy.

This study investigates neural processes in infant speech processing, with a focus on left frontal brain regions and hemispheric lateralization in Mandarin-speaking infants' acquisition of native tonal categories. We tested 2- to 6-month-old Mandarin learners to explore age-related improvements in tone discrimination, the role of inferior frontal regions in abstract speech category representation, and left hemisphere lateralization during tone processing. Using a block design, we presented four Mandarin tones via [ta] and measured oxygenated hemoglobin concentration with functional near-infrared spectroscopy. Results showed age-related improvements in tone discrimination, greater involvement of frontal regions in older infants indicating abstract tonal representation development and increased bilateral activation mirroring native adult Mandarin speakers. These findings contribute to our broader understanding of the relationship between native speech acquisition and infant brain development during the critical period of early language learning.

Degradation Behavior and Lifetime Prediction of Polyurea Anti-Seepage Coating for Concrete Lining in Water Conveyance Tunnels.

In the lining of water conveyance tunnels, the expansion joint is susceptible to leakage issues, significantly impacting the long-term safety of tunnel operations. Polyurea is a type of protective coating commonly used on concrete surfaces, offering multiple advantages such as resistance to seepage, erosion, and wear. Polyurea coatings are applied by spraying them onto the surfaces of concrete linings in water conveyance tunnels to seal the expansion joint. These coatings endure prolonged exposure to environmental elements such as water flow erosion, internal and external water pressure, and temperature variations. However, the mechanism of polyurea coating's long-term leakage prevention failure in tunnel operations remains unclear. This study is a field investigation to assess the anti-seepage performance of polyurea coating in a water conveyance tunnel project located in Henan Province, China. The testing apparatus can replicate the anti-seepage conditions experienced in water conveyance tunnels. An indoor accelerated aging test plan was formulated to investigate the degradation regular pattern of the cohesive strength between polyurea coating and concrete substrates. This study specifically examines the combined impacts of temperature, water flow, and water pressure on the performance of cohesive strength. The cohesive strength serves as the metric for predicting the service lifetime based on laboratory aging test data. This analysis aims to evaluate the polyurea coating's cohesive strength on the tunnel lining surface after five years of operation.

US-based Sequential Algorithm Integrating an AI Model for Advanced Liver Fibrosis Screening.

Background Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B-mode US of the liver between January 2014 and September 2022 at three health care facilities. A US-based DL network (FIB-Net) was trained on US images to predict whether the shear-wave elastography (SWE) value was 8.7 kPa or higher, indicative of advanced fibrosis. In the internal and external test sets, a two-step algorithm (Two-step#1) using the Fibrosis-4 Index (FIB-4) followed by FIB-Net and a three-step algorithm (Three-step#1) using FIB-4 followed by FIB-Net and SWE were used to simulate screening scenarios where liver stiffness measurements were not or were available, respectively. Measures of diagnostic accuracy were calculated using liver biopsy as the reference standard and compared between FIB-4, SWE, FIB-Net, and European Association for the Study of the Liver guidelines (ie, FIB-4 followed by SWE), along with sequential algorithms. Results The training, validation, and test data sets included 3067 (median age, 42 years [IQR, 33-53 years]; 2083 male), 1599 (median age, 41 years [IQR, 33-51 years]; 1124 male), and 1228 (median age, 44 years [IQR, 33-55 years]; 741 male) patients, respectively. FIB-Net obtained a noninferior specificity with a margin of 5% (P < .001) compared with SWE (80% vs 82%). The Two-step#1 algorithm showed higher specificity and positive predictive value (PPV) than FIB-4 (specificity, 79% vs 57%; PPV, 44% vs 32%) while reducing unnecessary referrals by 42%. The Three-step#1 algorithm had higher specificity and PPV compared with European Association for the Study of the Liver guidelines (specificity, 94% vs 88%; PPV, 73% vs 64%) while reducing unnecessary referrals by 35%. Conclusion A sequential algorithm combining FIB-4 and a US DL model showed higher diagnostic accuracy and improved referral management for all-cause advanced liver fibrosis compared with FIB-4 or the DL model alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ghosh in this issue.

PAX1 represses canonical Wnt signaling pathway and plays dual roles during endoderm differentiation.

BACKGROUND: Paired box 1 (PAX1) is a transcription factor and essential for the development of pharyngeal pouches-derived tissues, including thymus. PAX1 mutations are identified in Severe Combined Immunodeficiency (SCID) patients with Otofaciocervical Syndrome Type 2 (OTFCS2). However, despite the critical roles of PAX1 in embryonic development and diseases, detailed insights into its molecular mode of action are critically missing. METHODS: The repressing roles of PAX1 and SCID associated mutants on Wnt signaling pathway were investigated by luciferase reporter assays, qRT-PCR and in situ hybridization in HEK293FT, HCT116 cells and zebrafish embryos, respectively. Co-immunoprecipitation (co-IP) and western blotting assays were carried out to identify the molecular mechanisms underlying PAX1's role on Wnt signaling pathway. hESC based endoderm differentiation, flow cytometry, high-throughput sequencing data analysis, and qRT-PCR assays were utilized to determine the roles of PAX1 during endoderm differentiation. RESULTS: Here, we show that PAX1 represses canonical Wnt signaling pathway in vertebrate cells. Mechanically, PAX1 competes with SUMO E3 ligase PIASy to bind to TCF7L2, thus perturbing TCF7L2 SUMOylation level, further reducing its transcriptional activity and protein stability. Moreover, we reveal that PAX1 plays dual roles in hESC-derived definitive and foregut/pharyngeal endoderm cells, which give rise to the thymus epithelium, by inhibiting Wnt signaling. Importantly, our data show PAX1 mutations found in SCID patients significantly compromise the suppressing ability of PAX1 on Wnt signaling. CONCLUSIONS: Our study presents a novel molecular mode of action of PAX1 in regulation of canonical Wnt signaling and endoderm differentiation, thus providing insights for the molecular basis of PAX1 associated SCID, offering better understanding of the behavior of PAX1 in embryogenesis.