Exploration of diverse secondary metabolites from Penicillium brasilianum by co-culturing with Armillaria mellea.

Bioinformatic analysis revealed that the genomes of ubiquitous Penicillium spp. might carry dozens of biosynthetic gene clusters (BGCs), yet many clusters have remained uncharacterized. In this study, a detailed investigation of co-culture fermentation including the basidiomycete Armillaria mellea CPCC 400891 and the P. brasilianum CGMCC 3.4402 enabled the isolation of five new compounds including two bisabolene-type sesquiterpenes (arpenibisabolanes A and B), two carotane-type sesquiterpenes (arpenicarotanes A and B), and one polyketide (arpenichorismite A) along with seven known compounds. The assignments of their structures were deduced by the extensive analyses of detailed spectroscopic data, electronic circular dichroism spectra, together with delimitation of the biogenesis. Most new compounds were not detected in monocultures under the same fermentation conditions. Arpenibisabolane A represents the first example of a 6/5-fused bicyclic bisabolene. The bioassay of these five new compounds exhibited no cytotoxic activities in vitro against three human cancer cell lines (A549, MCF-7, and HepG2). Moreover, sequence alignments and bioinformatic analysis to other metabolic pathways, two BGCs including Pb-bis and Pb-car, responsible for generating sesquiterpenoids from co-culture were identified, respectively. Furthermore, based on the chemical structures and deduced gene functions of the two clusters, a hypothetic metabolic pathway for biosynthesizing induced sesquiterpenoids was proposed. These results demonstrated that the co-culture approach would facilitate bioprospecting for new metabolites even from the well-studied microbes. Our findings would provide opportunities for further understanding of the biosynthesis of intriguing sesquiterpenoids via metabolic engineering strategies. KEY POINTS: • Penicillium and Armillaria co-culture facilitates the production of diverse secondary metabolites • Arpenibisabolane A represents the first example of 6/5-fused bicyclic bisabolenes • A hypothetic metabolic pathway for biosynthesizing induced sesquiterpenoids was proposed.

Global, regional, and national burden of hearing loss in children and adolescents, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021.

BACKGROUND: Hearing loss in children and adolescents is attracting increasing attention as a growing public health problem. This study aimed to analyze the burden of hearing loss in children and adolescents from 1990 to 2021 to provide a new basis for further epidemiological research, disease prevention, and public health policy development. METHODS: The prevalence and years lived with disability (YLDs) of hearing loss in children and adolescents from 1990 to 2021 at the global, regional, and national levels were extracted from the Global Burden of Disease 2021 database. The estimated annual percentage change (EAPC) was used to assess trends in prevalence and YLDs. Pearson correlation analysis was used to assess the relationships between sociodemographic index (SDI) and prevalence and YLDs. RESULTS: In 2021, approximately 97.83 million children and adolescents under the age of 20 years were affected by hearing loss globally, resulting in approximately 3.91 million YLDs. From 1990 to 2021, the prevalence rate increased from 3537 per 100,000 to 3711 per 100,000, with an EAPC of 0.15% (95% CI: 0.12-0.17). The burden of hearing loss was greater in low-middle-SDI region and low-SDI region. Mild hearing loss accounted for 62.1% of the total cases and was the predominant type of hearing loss. Otitis media was the leading preventable cause of hearing loss, with 46.9% of hearing loss attributed to otitis media. Moreover, in children under 5 years of age, 68.7% of hearing loss was attributed to otitis media. Pearson correlation analysis revealed that the prevalence rates and YLDs rates of hearing loss were negatively correlated with the SDI (R = -0.57, P < 0.001; R = -0.64, P < 0.001). CONCLUSIONS: The burden of hearing loss in children and adolescents has increased over the past three decades and remains high. The burden is greater in less economically developed countries or regions. Policymakers should pay attention to the increasing burden of hearing loss in children and adolescents and take targeted measures to control this burden.

Assessment of 3.0 Tesla magnetic resonance imaging in Madelung's deformity: findings and implications.

OBJECTIVE: The aim of the study was to investigate the 3.0 Tesla magnetic resonance imaging (MRI) features of Madelung's deformity. MATERIALS AND METHODS: The wrist MRI scans of 19 patients clinically diagnosed with Madelung's deformity and 20 patients without deformity were consecutively selected from Beijing Jishuitan Hospital between April 2019 and December 2022 for observation, in the case group and control group, respectively. Multiple linear regression was used to analyze the factors affecting tilting angle and width of central disc (CD, also termed as triangular fibrocartilage, the main component of triangular fibrocartilage complex), while the chi-square test was used to compare the occurrences of CD (radial) attachment displacement, VL, and RTL. p < 0.05 indicated statistical significance. RESULTS: Madelung's deformity significantly contributed to the tilting and thickening of the CD. In the case group, the tilting angle and thickness of CD were (51.46 ± 1.33)° and (0.23 ± 0.01) cm, respectively, which was statistically significant (p < 0.05); the radial attachment of the CD significantly shifted away from the distal articular surface level (χ2 = 39.00, p < 0.001), with a mean displacement of (0.97 ± 0.38) cm. Furthermore, the cases demonstrated abnormally developed Vickers ligament (χ2 = 35.19, p < 0.001) and radiotriquetral ligament (χ2 = 25.66, p < 0.001). CONCLUSION: MRI provides a notable advantage in diagnosing Madelung's deformity. Compared with the control group, patients with Madelung's deformity exhibited tilting and thickening of the CD. Additionally, the radial attachment of the CD was significantly shifted proximally with abnormal development of Vickers and radiotriquetral ligaments.

FMCW Laser Fuze Structure with Multi-Channel Beam Based on 3D Particle Collision Scattering Model under Smoke Interference.

In the environment of smoke and suspended particles, the accurate detection of targets is one of the difficulties for frequency-modulated continuous-wave (FMCW) laser fuzes to work properly in harsh conditions. To weaken and eliminate the significant influence caused by the interaction of different systems in the photon transmission process and the smoke particle environment, it is necessary to increase the amplitude of the target echo signal to improve the signal-to-noise ratio (SNR), which contributes to enhancing the detection performance of the laser fuze for the ground target in the smoke. Under these conditions, the particle transmission of photons in the smoke environment is studied from the perspective of three-dimentional (3D) collisions between photons and smoke particles, and the modeling and Unity3D simulation of FMCW laser echo signal based on 3D particle collision is conducted. On this basis, a laser fuze structure based on multiple channel beam emission is designed for the combined effect of particle features from different systems and its impact on the target characteristics is researched. Simulation results show that the multiple channel laser emission enhances the laser target echo signal amplitude and also improves the anti-interference ability against the combined effects of multiple particle features compared with the single channel. Through the validation based on the laser prototype with four-channel beam emitting, the above conclusions are supported by the experimental results. Therefore, this study not only reveals the laser target properties under the 3D particle collision perspective, but also reflects the reasonableness and effectiveness of utilizing the target characteristics in the 3D particle collision mode to enhance the detection performance of FMCW laser fuze in the smoke.

Exosome-Mediated lncRNA LINC01140 Attenuates Breast Cancer Progression by Regulating the Wnt/ß-Catenin Pathway.

Exosome-delivered long non-coding RNAs have a role in the cancer control. It is unknown how exosomal LINC01140 contributes to the breast cancer (BC) growth. The purpose of this investigation is to identify exosomal LINC01140's function in the development of breast cancer. Using quantitative reverse transcripion polymerase chain reaction, the expression of LINC01140 was measured. To investigate how LINC01140 overexpression impacts BC cell proliferation, CCK-8 as well as colony formation assays (CFA) were employed. The expression of apoptosis-related proteins (Bax and Bcl-2) and Wnt/ß-catenin signal pathway-related proteins (Wnt, C-myc, ß-catenin, and p-GSK-3ß) was assessed through Western blotting. Exosomes from BC cells were verified by western blotting to measure CD63 and CD9 levels. To examine how exosomal LINC01140 affects Wnt/ß-catenin signaling pathway and xenograft tumor in nude mice, BC cell exosomes that were overexpressing LINC01140 were obtained and co-cultured with BC cells. In BC, it was discovered that LINC01140 had poor expression. BC cell proliferation was inhibited by overexpressing LINC01140, and the levels of the proteins Bcl-2, ß-catenin, C-myc, and Wnt were lowered while Bax and p-GSK-3 were increased. In addition, exosomal LINC01140 hindered the activation of the Wnt/ß-catenin signaling pathway, leading to a decrease in the growth of breast cancer cells in vivo. The presence of exosomal LINC01140 impedes the initiation of Wnt/ß-catenin and reduces the cancerous characteristics of BC cells.

Computer-aided diagnosis of early-stage colorectal cancer using nonmagnified endoscopic white-light images (with videos).

BACKGROUND AND AIMS: Differentiation of colorectal cancers (CRCs) with deep submucosal invasion (T1b) from CRCs with superficial invasion (T1a) or no invasion (Tis) is not straightforward. This study aimed to develop a computer-aided diagnosis (CADx) system to establish the diagnosis of early-stage cancers using nonmagnified endoscopic white-light images alone. METHODS: From 5108 images, 1513 lesions (Tis, 1074; T1a, 145; T1b, 294) were collected from 1470 patients at 10 academic hospitals and assigned to training and testing datasets (3:1). The ResNet-50 network was used as the backbone to extract features from images. Oversampling and focal loss were used to compensate class imbalance of the invasive stage. Diagnostic performance was assessed using the testing dataset including 403 CRCs with 1392 images. Two experts and 2 trainees read the identical testing dataset. RESULTS: At a 90% cutoff for the per-lesion score, CADx showed the highest specificity of 94.4% (95% confidence interval [CI], 91.3-96.6), with 59.8% (95% CI, 48.3-70.4) sensitivity and 87.3% (95% CI, 83.7-90.4) accuracy. The area under the characteristic curve was 85.1% (95% CI, 79.9-90.4) for CADx, 88.2% (95% CI, 83.7-92.8) for expert 1, 85.9% (95% CI, 80.9-90.9) for expert 2, 77.0% (95% CI, 71.5-82.4) for trainee 1 (vs CADx; P = .0076), and 66.2% (95% CI, 60.6-71.9) for trainee 2 (P < .0001). The function was also confirmed on 9 short videos. CONCLUSIONS: A CADx system developed with endoscopic white-light images showed excellent per-lesion specificity and accuracy for T1b lesion diagnosis, equivalent to experts and superior to trainees. (Clinical trial registration number: UMIN000037053.).

Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

OBJECTIVES: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). METHODS: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). RESULTS: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (ß, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. CONCLUSIONS: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. KEY POINTS: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

Is Hip Medial Ultrasound More Accurate Than Radiography for Determining the Status of Hip Reduction in Children Treated With a Spica Cast? A Retrospective Diagnostic Accuracy Study.

BACKGROUND: Developmental dysplasia of the hip (DDH) is the most common hip abnormality in children. Closed or open reduction and cast immobilization are the most commonly used treatments for patients aged 6 to 18 months with dislocation; they are also used in children younger than 6 months when brace treatment is not effective. During cast immobilization, surgeons need reliable and timely imaging methods to assess the status of hip reduction to ensure successful treatment and avoid complications. Several methods are used, but they have disadvantages. We developed and, in this study, evaluated a hip medial ultrasound method to evaluate the status of hip reduction in children treated with a spica cast. QUESTION/PURPOSE: Is hip medial ultrasound more accurate than radiography for determining the status of hip reduction in children treated with a spica cast? METHODS: Between November 2017 and December 2020, we treated 136 patients with closed or open reduction and spica casting for DDH in our department. These children were 3 to 18 months old at the time of surgical reduction and had a specific medical history, physical examination findings, or AP radiographic evidence of unilateral or bilateral DDH. None had a concomitant femoral/acetabular osteotomy procedure in these hips. All patients underwent hip medial ultrasound, AP radiography, and MRI under sedation within 2 to 7 days after open or closed reduction. The examination time was from the second day after reduction to enable the patient to recover from anesthesia. MRI was performed within 7 days after reduction because of a few long appointment times, and ultrasound and AP radiography were always performed 1 or 2 days before MRI. Based on that, 65% (88 of 136 [88 hips]) of patients were excluded due to the absence of MRI, ultrasound, or AP radiography; 3% (4 of 136 [4 hips]) of patients were excluded because of concurrent congenital spina bifida, Larson syndrome, or Prader-Willi syndrome; and 1% (1 of 136 [1 hip]) of patients were excluded because the patient underwent MRI before ultrasound. A total of 32% (43 of 136 [43 hips]) of patients were eligible for analysis in this cross-sectional diagnostic study, and these 43 patients underwent AP radiography, ultrasound, and MRI. In this retrospective study, the mean age at the time of surgery was 10 ± 4 months (male:female ratio 5:38; unilateral DDH: 34; bilateral DDH: 9). To ensure the independence of the results, the study was limited to one hip per patient (in patients with bilateral DDH, the right hip was evaluated). The reduction of 43 hips (left:right ratio 26:17; closed:open reduction ratio 30:13) was evaluated by MRI, hip medial ultrasound, and radiography. Children with spica casts were placed in the supine position, which is necessary to expose the perineum for ultrasound. We used a broad-spectrum, microconvex, and intracavitary probe. The acetabular medial wall was identified by the triradiate cartilage of the ischial tuberosity and the pubis superior, and the femoral head was identified by the femoral neck. Then, the acetabulum coronal midsectional plane was used to determine the positions of the femoral head and acetabulum and to measure the triradiate cartilage-femoral distance. MRI examinations were performed using a 1.5-T MRI system with an eight-channel body coil. Each reviewer evaluated each reduction independently. Additionally, to further assess the hip medial ultrasound method's reliability and reproducibility, we investigated the interobserver and intraobserver agreement in evaluating the reduction using hip medial ultrasound. Using ultrasound or radiography, the reviewers classified hips as reduced, uncertain status, or dislocated. MRI was considered the gold standard for assessing hip reduction, and the reviewers classified hips as reduced or dislocated by MRI. Patients with hips with an uncertain reduction status according to ultrasound or radiography were retained in the analysis. Thus, the test results of radiography and ultrasound were classified into three classifications (positive, negative, or uncertain) in the present study. The test was considered positive or negative when patients were assessed with dislocation or without dislocation, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ultrasound and radiography were calculated and compared. We combined uncertain and positive into the positive classification to be conservative in the statistical choices. The specificity, sensitivity, PPV, and NPV were analyzed based on this premise. Furthermore, a subgroup analysis was conducted by sex. MRI evaluation revealed that 41 hips were reduced and two hips were dislocated. RESULTS: The sensitivity, specificity, PPV, and NPV of ultrasound were 100% (95% CI 16% to 100%), 95% (95% CI 84% to 99%), 50% (95% CI 7% to 93%), and 100% (95% CI 91% to 100%), respectively. The sensitivity, specificity, PPV, and NPV of radiography were 50% (95% CI 1% to 99%), 68% (95% CI 52% to 82%), 7% (95% CI 0% to 34%), and 97% (95% CI 82% to 100%), respectively. Ultrasound showed a higher specificity (95% versus 68%; p < 0.001) and PPV (50% versus 7%; p = 0.02) than radiography. The sensitivity, specificity, PPV, and NPV of ultrasound were 100% (95% CI 16% to 100%), 94% (95% CI 81% to 99%), 50% (95% CI 7% to 93%), and 100% (95% CI 90% to 100%), respectively, for female patients (with only five male patients, we could not perform these analyses in this group). The sensitivity, specificity, PPV, and NPV of radiography were 50% (95% CI 1% to 99%), 64% (95% CI 46% to 79%), 7% (95% CI 0% to 34%), and 96% (95% CI 79% to 100%), respectively, for female patients. The κ values for intra- and interobserver reliability both were 1.0. CONCLUSION: Hip medial ultrasound can directly visualize the femoral head and acetabulum. Hip medial ultrasound is more reliable than radiography as a preliminary evaluation method and does not involve irradiation. We recommend using hip medial ultrasound during outpatient follow-up visits for patients younger than 2 years treated with hip reduction and cast immobilization. LEVEL OF EVIDENCE: Level III, diagnostic study.

Exploring the Role of Different Cell-Death-Related Genes in Sepsis Diagnosis Using a Machine Learning Algorithm.

Sepsis, a disease caused by severe infection, has a high mortality rate. At present, there is a lack of reliable algorithmic models for biomarker mining and diagnostic model construction for sepsis. Programmed cell death (PCD) has been shown to play a vital role in disease occurrence and progression, and different PCD-related genes have the potential to be targeted for the treatment of sepsis. In this paper, we analyzed PCD-related genes in sepsis. Implicated PCD processes include apoptosis, necroptosis, ferroptosis, pyroptosis, netotic cell death, entotic cell death, lysosome-dependent cell death, parthanatos, autophagy-dependent cell death, oxeiptosis, and alkaliptosis. We screened for diagnostic-related genes and constructed models for diagnosing sepsis using multiple machine-learning models. In addition, the immune landscape of sepsis was analyzed based on the diagnosis-related genes that were obtained. In this paper, 10 diagnosis-related genes were screened for using machine learning algorithms, and diagnostic models were constructed. The diagnostic model was validated in the internal and external test sets, and the Area Under Curve (AUC) reached 0.7951 in the internal test set and 0.9627 in the external test set. Furthermore, we verified the diagnostic gene via a qPCR experiment. The diagnostic-related genes and diagnostic genes obtained in this paper can be utilized as a reference for clinical sepsis diagnosis. The results of this study can act as a reference for the clinical diagnosis of sepsis and for target discovery for potential therapeutic drugs.

Ferroelectric Nanogap-Based Steep-Slope Ambipolar Transistor.

The subthreshold swing (SS) of metal-oxide-semiconductor field-effect transistors is limited to 60 mV dec-1 at room temperature by the Boltzmann tyranny, which restricts the scaling of the supply voltage. A nanogap-based transistor employs a switchable nanoscale air gap as the channel, offering a steep-slope switching process. Meanwhile, nanogaps featuring even sub-3 nm can efficiently block the current flow, exhibiting the potential for tackling the short-channel effect. Here, an electrically switchable ferroelectric nanogap to construct steep-slope transistors, is exploited. An average SS of 15.9 mV dec-1 across 5 orders and a minimum SS of 13.23 mV dec-1 are obtained in the high current density range. The transistor exhibits excellent performance with near-zero off-state leakage current and a maximum on-state current of 202 µA µm-1 at VDS  = 0.5 V. In addition, the transistor can turn off with either a positive or negative increase in the gate voltage, exhibiting ambipolar characteristics.

Photonic generation of frequency-tunable biphase and quadriphase coded pulse signals without background interference enabled by vector modulation and balanced detection.

An approach to generating frequency-tunable biphase and quadriphase coded pulse signals without background interference based on a polarization division multiplexing dual-parallel Mach-Zehnder modulator (PDM-DPMZM) is presented and demonstrated. Two ternary baseband code sequences are separately encoded into a pair of orthogonal optical carriers by exploiting a polyphase encoder on the basis of the principle of vector modulation, which in turn can be mapped to the phase shifts of the generated phase coded waveforms after the balanced detection. The frequency tunability can also be achieved by controlling the bias voltage of the associated modulator, so that the carrier frequency can be tuned to either fundamental or doubled frequency. Additionally, by designing different phase codes, the generated pulse signals can be conveniently switched between the quadriphase and biphase coding waveforms. The major advantage of the proposed approach is that four phase shifts can be obtained by simply adjusting the polarity of the ternary code sequences, overcoming the power-dependent limitation of the previous work. A proof-of-principle experiment is conducted to assess the feasibility of the proposed approach built on the Barker code and Frank code phase coded pulse signals generation. Experimental results show the phase coded pulse signals at 12 and 24 GHz carrier frequency are well behaved in terms of peak-to-sidelobe ratio (PSR), range-Doppler coupling and Doppler tolerance.

Responses of the tree peony (Paeonia suffruticosa, Paeoniaceae) cultivar 'Yu Hong' to heat stress revealed by iTRAQ-based quantitative proteomics.

Horticulture productivity has been increasingly restricted by heat stress from growing global warming, making it far below the optimum production capacity. As a popular ornamental cultivar of tree peony, Paeonia suffruticosa 'Yu Hong' has also been suffering from heat stress not suitable for its optimal growth. To better understand the response mechanisms against heat stress of tree peony, investigations of phenotypic changes, physiological responses, and quantitative proteomics were conducted. Phenotypic and physiological changes indicated that 24 h of exposure to heat stress (40 °C) was the critical duration of heat stress in tree peony. The proteomic analyses revealed a total of 100 heat-responsive proteins (HRPs). According to bioinformatic analysis of HRPs, the heat tolerance of tree peony might be related to signal transduction, synthesis/degradation, heat kinetic proteins, antioxidants, photosynthesis, energy conversion, and metabolism. Our research will provide some new insights into the molecular mechanism under the response against the heat stress of tree peony, which will benefit the future breeding of heat-resistant ornamental plants.

BCL2L1 is identified as a target of naringenin in regulating ovarian cancer progression.

Naringenin is a natural bioactive flavonoid with a wide spectrum of biological activities, including anti-carcinogenic ability. Our study aimed to investigate the effect of naringenin on ovarian cancer (OC) progression. Naringenin was input into PharmMapper and SwissTargetPrediction databases to predict its targets, and OC-related targets were obtained using MalaCards and GEPIA databases, which were imported into online Venn tool to identify the common targets. B-cell lymphoma-2 like 1 (BCL2L1) expression in OC tissues and cells was detected using GEPIA and HPA databases, qRT-PCR and Western blot analysis. The prognostic and diagnostic values of BCL2L1 in OC were determined using Kaplan-Meier plotter tool and receiver operating characteristic (ROC) curve analysis, respectively. Cell proliferation was evaluated using CCK-8 and EdU incorporation assays. Cell apoptosis was determined using TUNEL and caspase-3 activity assays. Effect of naringenin on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway was evaluated by Western blot analysis. BCL2L1 was identified as the candidate target of naringenin against OC. BCL2L1 was upregulated in OC tissues and cells. Naringenin decreased BCL2L1 expression and inactivated the PI3K/Akt pathway in OC cells. Naringenin inhibited cell proliferation and increased the apoptotic rate in OC cells, while these effects were partially abolished by BCL2L1 overexpression and treatment with 740Y-P, a PI3K activator. In conclusion, naringenin exerted an anti-tumor effect on OC progression via inactivation of the PI3K/Akt/BCL2L1 pathway.

Hepatic Steatosis: CT-Based Prevalence in Adults in China and the United States and Associations With Age, Sex, and Body Mass Index.

BACKGROUND. Calibrated CT fat fraction (FFCT) measurements derived from un-enhanced abdominal CT reliably reflect liver fat content, allowing large-scale population-level investigations of steatosis prevalence and associations. OBJECTIVE. The purpose of this study was to compare the prevalence of hepatic steatosis, as assessed by calibrated CT measurements, between population-based Chinese and U.S. cohorts, and to investigate in these populations the relationship of steatosis with age, sex, and body mass index (BMI). METHODS. This retrospective study included 3176 adults (1985 women and 1191 men) from seven Chinese provinces and 8748 adults (4834 women and 3914 men) from a single U.S. medical center, all drawn from previous studies. All participants were at least 40 years old and had undergone unenhanced abdominal CT in previous studies. Liver fat content measurements on CT were cross-calibrated to MRI proton density fat fraction measurements using phantoms and expressed as adjusted FFCT measurements. Mild, moderate, and severe steatosis were defined as adjusted FFCT of 5.0-14.9%, 15.0-24.9%, and 25.0% or more, respectively. The two cohorts were compared. RESULTS. In the Chinese and U.S. cohorts, the median adjusted FFCT for women was 4.7% and 4.8%, respectively, and that for men was 5.8% and 6.2%, respectively. In the Chinese and U.S. cohorts, steatosis prevalence for women was 46.3% and 48.7%, respectively, whereas that for men was 58.9% and 61.9%, respectively. Severe steatosis prevalence was 0.9% and 1.8% for women and 0.2% and 2.6% for men in the Chinese and U.S. cohorts, respectively. Adjusted FFCT did not vary across age decades among women or men in the Chinese cohort, although it increased across age decades among women and men in the U.S. cohort. Adjusted FFCT and BMI exhibited weak correlation (r = 0.312-0.431). Among participants with normal BMI, 36.8% and 38.5% of those in the Chinese and U.S. cohorts, respectively, had mild steatosis, and 3.0% and 1.5% of those in the Chinese and U.S. cohorts, respectively, had moderate or severe steatosis. Among U.S. participants with a BMI of 40.0 or greater, 17.7% had normal liver content. CONCLUSION. Steatosis and severe steatosis had higher prevalence in the U.S. cohort than in the Chinese cohort in both women and men. BMI did not reliably predict steatosis. CLINICAL IMPACT. The findings provide new information on the dependence of hepatic steatosis on age, sex, and BMI.

Computer-aided diagnosis of serrated colorectal lesions using non-magnified white-light endoscopic images.

PURPOSE: Computer-aided diagnosis systems for polyp characterization are commercially available but cannot recognize subtypes of sessile lesions. This study aimed to develop a computer-aided diagnosis system to characterize polyps using non-magnified white-light endoscopic images. METHODS: A total of 2249 non-magnified white-light images from 1030 lesions including 534 tubular adenomas, 225 sessile serrated adenoma/polyps, and 271 hyperplastic polyps in the proximal colon were consecutively extracted from an image library and divided into training and testing datasets (4:1), based on the date of colonoscopy. Using ResNet-50 networks, we developed a classifier (1) to differentiate adenomas from serrated lesions, and another classifier (2) to differentiate sessile serrated adenoma/polyps from hyperplastic polyps. Diagnostic performance was assessed using the testing dataset. The computer-aided diagnosis system generated a probability score for each image, and a probability score for each lesion was calculated as the weighted mean with a log10-transformation. Two experts (E1, E2) read the identical testing dataset with a probability score. RESULTS: The area under the curve of classifier (1) for adenomas was equivalent to E1 and superior to E2 (classifier 86%, E1 86%, E2 69%; classifier vs. E2, p < 0.001). In contrast, the area under the curve of classifier (2) for sessile serrated adenoma/polyps was inferior to both experts (classifier 55%, E1 68%, E2 79%; classifier vs. E2, p < 0.001). CONCLUSION: The classifier (1) developed using white-light images alone compares favorably with experts in differentiating adenomas from serrated lesions. However, the classifier (2) to identify sessile serrated adenoma/polyps is inferior to experts.

Identifying the neural basis for rosacea using positron emission tomography-computed tomography cerebral functional imaging analysis: A cross-sectional study.

BACKGROUND: The neural basis of rosacea is not well understood. This study aimed to determine whether cerebral glucose metabolism (CGM) changes on 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET)/computed tomography (CT) scans can detect functional network changes in specific brain areas in patients with rosacea. MATERIALS AND METHODS: Eight adults with rosacea and 10 age/sex-matched healthy adults (controls) were enrolled in the study. 18 F-FDG PET/CT brain images for all eight patients and whole-body images for two of the patients were analyzed qualitatively and semi-quantitatively. Differences between the study groups were examined using Fischer's exact test and a Student's t-test. A voxel-based analysis using statistical parametric mapping was performed to compare the brain metabolism of the patients with that of the controls. RESULTS: Compared with the controls, the patients with rosacea showed extensive changes in the CGM signals in the cerebral cortex and limbic system, with less CGM shown in the right superior parietal lobule, right postcentral gyrus, right parahippocampal gyrus, left superior frontal gyrus, and lateral posterior thalamic nucleus and more CGM in the right precentral gyrus, left inferior frontal gyrus, and cerebellar tonsil. No dysmetabolic lesions were found in the whole-body 18 F-FDG PET/CT images. CONCLUSION: Specific neural functional changes occur in patients with rosacea that may explain its pathogenesis.

Species Difference in the Metabolism of Mulberrin in Vitro and Its Inhibitory Effect on Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes.

This study aimed to evaluate the interspecies difference in metabolism of mulberrin and examine the interaction between mulberrin and CYP enzymes or recombinant human uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT) enzymes. Liver microsomes from human (HLMs), Beagle dog (DLMs), minipig (PLMs), monkey (MLMs), rabbit (RLMs), rat (RAMs), and mouse (MIMs) were used to investigate metabolic diversity among different species. Additionally, recombinant human supersomes were used to confirm that metabolic enzymes are involved in the biotransformation of mulberrin. We also evaluated the influence of mulberrin on protein expression by Western blot analysis. Mulberrin metabolism showed significant interspecies differences. We found four and two metabolites in phase I and II reaction systems, respectively. In phase I metabolism profiles of mulberrin for HLMs, PLMs and MLMs conformed to the classic Michaelis-Menten kinetics, RAMs and MIMs followed biphasic kinetics; phase II reaction of mulberrin in HLMs, DLMs, PLMs, MLMs, RLMs, RAMs and MIMs followed biphasic kinetics. UGT1A1 were the major CYP isoforms responsible for the metabolism of mulberrin. Mulberrin showed potent inhibitory effects against CYP3A4, CYP2C9, CYP2E1, UGT1A1, UGT1A3 and UGT2B7 with IC50 values of 54.21, 9.93, 39.12, 3.84, 2.01, 16.36 µM, respectively. According to Western blot analysis, mulberrin can upregulate the protein expression of CYP2C19, and downregulate the expression levels of CYP3A5 and CYP2C9 in HepG2 cells as concentration increased. The interspecies comparisons can help find other species with metabolic pathways similar to those in humans for future in vivo studies.

In vitro differences in toddalolactone metabolism in various species and its effect on cytochrome P450 expression.

CONTEXT: Toddalolactone, the main component of Toddalia asiatica (L.) Lam. (Rutaceae), has anticancer, antihypertension, anti-inflammatory, and antifungal activities. OBJECTIVE: This study investigated the metabolic characteristics of toddalolactone. MATERIALS AND METHODS: Toddalolactone metabolic stabilities were investigated by incubating toddalolactone (20 µM) with liver microsomes from humans, rabbits, mice, rats, dogs, minipigs, and monkeys for 0, 30, 60, and 90 min. The CYP isoforms involved in toddalolactone metabolism were characterized based on chemical inhibition studies and screening assays. The effects of toddalolactone (0, 10, and 50 µM) on CYP1A1 and CYP3A5 protein expression were investigated by immunoblotting. After injecting toddalolactone (10 mg/kg), in vivo pharmacokinetic profiles using six Sprague-Dawley rats were investigated by taking 9-time points, including 0, 0.25, 0.5, 0.75, 1, 2, 4, 6 and 8 h. RESULTS: Monkeys showed the greatest metabolic capacity in CYP-mediated and UGT-mediated reaction systems with short half-lives (T1/2) of 245 and 66 min, respectively, while T1/2 of humans in two reaction systems were 673 and 83 min, respectively. CYP1A1 and CYP3A5 were the major CYP isoforms involved in toddalolactone biotransformation. Induction of CYP1A1 protein expression by 50 µM toddalolactone was approximately 50% greater than that of the control (0 µM). Peak plasma concentration (Cmax) for toddalolactone was 0.42 µg/mL, and Tmax occurred at 0.25 h post-dosing. The elimination t1/2 was 1.05 h, and the AUC0-t was 0.46 µg/mL/h. CONCLUSIONS: These findings demonstrated the significant species differences of toddalolactone metabolic profiles, which will promote appropriate species selection in further toddalolactone studies.

TWIST1 transcriptionally regulates glycolytic genes to promote the Warburg metabolism in pancreatic cancer.

Reprogrammed glucose metabolism is essential for tumor initiation and development, especially for pancreatic ductal adenocarcinoma (PDAC). Most cancer cells rely on aerobic glycolysis, a phenomenon termed "the Warburg effect", to support uncontrolled proliferation and evade apoptosis. However, the direct regulators of the Warburg effect remain areas of active investigation. In this study, we found that the highly conserved transcription factor, TWIST1, is a crucial regulator of aerobic glycolysis in PDAC. Genetic silencing of TWIST1 significantly inhibited the glycolytic phenotypes of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate, which can be restored by re-expression of siRNA-resistant TWIST1. Moreover, tamoxifen-inducible expression of TWIST1 promoted the Warburg metabolism of PDAC cells. Mechanistically, by luciferase reporter assay and chromatin immunoprecipitation experiment, we showed that TWIST1 can directly increase the expression of several glycolytic genes, including SLC2A1, HK2, ENO1, and PKM2. Of note, the transcriptional regulation by TWIST1 was not dependent on HIF1α or c-Myc. In The Cancer Genome Atlas and Gene Expression Omnibus accession GSE15471, we confirmed that TWIST1 was closely associated with the glycolysis pathway. Collectively, our findings indicate that TWIST1 is likely to act as important regulator of the Warburg effect in PDAC.

The differential effects of vowel and onset consonant lengthening on speech segmentation: Evidence from Taiwanese Southern Min.

A review of previous speech segmentation research suggests the prediction that listeners of Taiwanese Southern Min (TSM), a lexical tone language, would exploit vowel lengthening and syllable-onset consonant lengthening to locate word ends and beginnings, respectively. Yet, correlations between segment duration and tone identity in tone languages along with some TSM-specific phonological phenomena may work against such use. Two artificial language learning experiments examined TSM listeners' use of the lengthening cues. The listeners heard the words of an artificial language (e.g., /ba.nu.me/) repeated continuously and identified them in a subsequent two-alternative forced-choice test. Experiment I revealed that their segmentation benefits from and only from word-initial onset lengthening or word-final vowel lengthening, supporting the prediction. Experiment II further demonstrated that these two cues in combination synergistically support segmentation at least when compared to word-initial onset lengthening alone, consistent with previous findings regarding complementary cues. These results furnish additional evidence that vowel and onset consonant lengthening affect segmentation in different ways, possibly reflecting a functional division between vowels and consonants that is supported by some prosody-computing mechanism. Additionally, vowel lengthening seems to affect segmentation to a greater extent than onset consonant lengthening. Possible explanations for this and further issues are discussed.