Cep57 regulates human centrosomes through multivalent interactions.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.

Precise control of microtubule disassembly in living cells.

Microtubules tightly regulate various cellular activities. Our understanding of microtubules is largely based on experiments using microtubule-targeting agents, which, however, are insufficient to dissect the dynamic mechanisms of specific microtubule populations, due to their slow effects on the entire pool of microtubules. To overcome this technological limitation, we have used chemo and optogenetics to disassemble specific microtubule subtypes, including tyrosinated microtubules, primary cilia, mitotic spindles, and intercellular bridges, by rapidly recruiting engineered microtubule-cleaving enzymes onto target microtubules in a reversible manner. Using this approach, we show that acute microtubule disassembly swiftly halts vesicular trafficking and lysosomal dynamics. It also immediately triggers Golgi and ER reorganization and slows the fusion/fission of mitochondria without affecting mitochondrial membrane potential. In addition, cell rigidity is increased after microtubule disruption owing to increased contractile stress fibers. Microtubule disruption furthermore prevents cell division, but does not cause cell death during interphase. Overall, the reported tools facilitate detailed analysis of how microtubules precisely regulate cellular architecture and functions.

Independent insulin signaling modulators govern hot avoidance under different feeding states.

Thermosensation is critical for the survival of animals. However, mechanisms through which nutritional status modulates thermosensation remain unclear. Herein, we showed that hungry Drosophila exhibit a strong hot avoidance behavior (HAB) compared to food-sated flies. We identified that hot stimulus increases the activity of α'ß' mushroom body neurons (MBns), with weak activity in the sated state and strong activity in the hungry state. Furthermore, we showed that α'ß' MBn receives the same level of hot input from the mALT projection neurons via cholinergic transmission in sated and hungry states. Differences in α'ß' MBn activity between food-sated and hungry flies following heat stimuli are regulated by distinct Drosophila insulin-like peptides (Dilps). Dilp2 is secreted by insulin-producing cells (IPCs) and regulates HAB during satiety, whereas Dilp6 is secreted by the fat body and regulates HAB during the hungry state. We observed that Dilp2 induces PI3K/AKT signaling, whereas Dilp6 induces Ras/ERK signaling in α'ß' MBn to regulate HAB in different feeding conditions. Finally, we showed that the 2 α'ß'-related MB output neurons (MBONs), MBON-α'3 and MBON-ß'1, are necessary for the output of integrated hot avoidance information from α'ß' MBn. Our results demonstrate the presence of dual insulin modulation pathways in α'ß' MBn, which are important for suitable behavioral responses in Drosophila during thermoregulation under different feeding states.

Actin filaments form a size-dependent diffusion barrier around centrosomes.

The centrosome, a non-membranous organelle, constrains various soluble molecules locally to execute its functions. As the centrosome is surrounded by various dense components, we hypothesized that it may be bordered by a putative diffusion barrier. After quantitatively measuring the trapping kinetics of soluble proteins of varying size at centrosomes by a chemically inducible diffusion trapping assay, we find that centrosomes are highly accessible to soluble molecules with a Stokes radius of less than 5.8 nm, whereas larger molecules rarely reach centrosomes, indicating the existence of a size-dependent diffusion barrier at centrosomes. The permeability of this barrier is tightly regulated by branched actin filaments outside of centrosomes and it decreases during anaphase when branched actin temporally increases. The actin-based diffusion barrier gates microtubule nucleation by interfering with γ-tubulin ring complex recruitment. We propose that actin filaments spatiotemporally constrain protein complexes at centrosomes in a size-dependent manner.

Site-directed biochemical analyses reveal that the switchable C-terminus of Rpc31 contributes to RNA polymerase III transcription initiation.

Rpc31 is a subunit in the TFIIE-related Rpc82/34/31 heterotrimeric subcomplex of Saccharomyces cerevisiae RNA polymerase III (pol III). Structural analyses of pol III have indicated that the N-terminal region of Rpc31 anchors on Rpc82 and further interacts with the polymerase core and stalk subcomplex. However, structural and functional information for the C-terminal region of Rpc31 is sparse. We conducted a mutational analysis on Rpc31, which uncovered a functional peptide adjacent to the highly conserved Asp-Glu-rich acidic C-terminus. This C-terminal peptide region, termed 'pre-acidic', is important for optimal cell growth, tRNA synthesis, and stable association of Rpc31 in the pre-initiation complex (PIC). Our site-directed photo-cross-linking to map protein interactions within the PIC reveal that this pre-acidic region specifically targets Rpc34 during transcription initiation, but also interacts with the DNA entry surface in free pol III. Thus, we have uncovered a switchable Rpc31 C-terminal region that functions in an initiation-specific protein interaction for pol III transcription.

Association of blood lipid profiles and asthma: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Observational studies and meta-analyses have indicated associations between blood lipid profiles and asthma. However, the causal association is unknown. Therefore, this study investigated the causal relationship between blood lipid profiles and asthma using bidirectional Mendelian randomization analysis. METHODS AND MATERIALS: Our analyses were performed using individual data from the Taiwan Biobank and summary statistics from the Asian Genetic Epidemiology Network (AGEN). The causal estimates between all genetic variants, exposures of interest and asthma were calculated using an inverse-variance weighted method based on Taiwan Biobank data from 24,853 participants (mean age, 48.8 years; 49.8% women). Sensitivity analyses, including the weighted median, MR Egger regression, MR-PRESSO, mode-based estimate, contamination mixture methods, and leave-one-out analysis, were applied to validate the results and detect pleiotropy. RESULTS: In the inverse-variance weighted (IVW) analyses, we found evidence of a significant causal effect of an increased level of low-density lipoprotein cholesterol on asthma risk (ßIVW = 1.338, p = 0.001). A genetically decreased level of high-density lipoprotein cholesterol was also associated with asthma risk (ßIVW = -0.338, p = 0.01). We also found that an increased level of total cholesterol was associated with an increased risk of asthma (ßIVW = 1.343, p = 0.001). Several sensitivity analyses generated consistent findings. We did not find evidence to support the causality between asthma and blood lipid profiles in either direction. CONCLUSION: Our results supported the causal relationship between higher levels of LDL cholesterol and total cholesterol and lower levels of HDL cholesterol with an increased risk of asthma.

Aflatoxin B1-exposed hepatocyte-derived extracellular vesicles: Initiating hepatic stellate cell-mediated liver fibrosis through a p53-Parkin-dependent mitophagy pathway.

Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.

Effects of Shoulder Corrective Training Program on Pitching Loads and Sonographic Morphology in Elbow Joint in Youth Baseball Players.

ABSTRACT: Chen, P-T, Lin, Y-C, Chang, H-Y, Chiu, C-H, Chen, C-Y, Chen, P, and Lin, Y-H. Effects of shoulder corrective training program on pitching loads and sonographic morphology in elbow joint in youth baseball players. J Strength Cond Res 38(8): e440-e447, 2024-We assessed the effects of a 12-week shoulder corrective training program for shoulder flexibility and strengthening on pitching loads and sonographic morphology of the elbow joints in youth baseball players. Seventeen subjects were recruited and underwent evaluations before and after the training program. We found that following training, subjects demonstrated significantly increased ranges of shoulder internal rotation (38.9 ± 12.9° vs. 69.2 ± 10.8°, p < 0.001), external rotation (91.2 ± 14.6° vs. 107.3 ± 9.5°, p = 0.004), and horizontal adduction (21.5 ± 8.0° vs. 32.7 ± 7.3°, p = 0.002); improved strength in the shoulder internal rotators (8.7 ± 1.6 kg vs. 9.8 ± 2.1 kg, p = 0.04), external rotators (6.5 ± 1.9 kg vs. 7.5 ± 2.8 kg, p = 0.04), middle trapezius (12.7 ± 2.1 kg vs. 14.3 ± 2.4 kg, p = 0.04), and middle deltoid muscles (10.8 ± 3.3 kg vs. 14.8 ± 3.2 kg, p = 0.001); and decreased thickness of the ulnar collateral ligament (6.1 ± 0.6 mm vs. 4.8 ± 0.7 mm, p = 0.002). Although there was no substantial change in elbow torque and arm speed, significantly increased ball speed (51.2 ± 4.6 mph vs. 54.1 ± 4.5 mph, p < 0.001) and decreased arm slot (63.8 ± 11.9° vs. 53.0 ± 12.7°, p = 0.02) were observed. We suggest that adequate corrective training should be performed regularly to minimize or mitigate adverse soft tissue changes at the elbow in youth baseball players. Balanced shoulder strength and flexibility may decrease medial elbow stress during pitching. Future studies should consider the kinetic and kinematic effects of other corrective training programs on the shoulder or elbow joint during pitching.

Effect of postprocessing parameters on the flexural strength of vat-polymerized additively manufactured interim fixed dental prostheses: A systematic review with postprocessing guidelines.

STATEMENT OF PROBLEM: Limited data exist regarding the effects of postprocessing on the flexural strength of vat-polymerized additively manufactured (AM) interim fixed dental prostheses. PURPOSE: The purpose of this systematic review was to determine how the postprocessing workflow affects the mechanical properties of vat-polymerized additively manufactured interim fixed dental prostheses and to establish clinical guidelines. MATERIAL AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The population, intervention, comparison, and outcome (PICO) question was "For vat-polymerized additively manufactured interim fixed dental prostheses (P), does varying the postprocessing workflow/ protocol (I and C) affect mechanical properties/physical properties/flexural strength (O)?" Searches were conducted in 3 databases: PubMed/Medline, EMBASE, and Web of Science, with 2 investigators performing the title and abstract screening and setting the inclusion and exclusion criteria to identify publications. The risk of bias was evaluated by applying the Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies (nonrandomized experimental studies). The reported independent variables of rinse solution, rinse time, and polymerization time on the flexural strength results were extracted for qualitative review. RESULTS: The initial search identified 149 records, with 12 in vitro studies meeting the inclusion criteria. Significant heterogeneity was observed in the manufacturing process and materials. Eleven of 12 included studies reported flexural strength above 100 MPa when following the manufacturer's recommendation. Postprocessing rinsing ranged from 5 seconds to 90 minutes, with potentially reduced flexural strength with extended rinsing. A rinse of 5 to 10 minutes was recommended for optimal mechanical properties, degree of conversion, and biocompatibility. Isopropyl alcohol (IPA) and tripropylene glycol monomethyl ether (TPM) were the most investigated rising solutions, while experimental solutions including 99.5% acetone and 100% bio-ethyl alcohol reportedly decreased flexural strength. Polymerization time and intensity correlated positively with the flexural strength, whereas an artificial aging process reduced the flexural strength. CONCLUSIONS: Heterogeneity existed in the reported postprocessing protocols for AM interim fixed prostheses, including manufacturer materials, methods, and study outcomes. While polymerization time and intensity correlated with greater strength, consistent patterns regarding rinsing solution or time were lacking. Rinsing solution, extended rinsing time, and artificial aging may reduce flexural strength. Further investigation is indicated.

Shade match comparison of CAD-CAM single crowns to a lithium disilicate crown.

PURPOSE: To assess the shade match ability of four varieties of all-ceramic crowns to a neighboring bilayered lithium disilicate crown. MATERIAL AND METHODS: A dentiform was used to fabricate a bilayered lithium disilicate crown on the maxillary right central incisor, following the anatomy and shade of a selected natural tooth. Two crowns (one full-contour, one cutback) were then designed on a prepared maxillary left central incisor, following the contour of the neighboring crown. The designed crowns were used to manufacture monolithic lithium disilicate, bilayered lithium disilicate, bilayered zirconia, and monolithic zirconia crowns, 10 each. An intraoral scanner and a spectrophotometer were used to assess the frequency of matched shades and to calculate the color difference (ΔE) between the two central incisors at the incisal, middle, and cervical thirds. Kruskal-Wallis and two-way ANOVA were used to compare the frequency of matched shades and ΔE values, respectively (α = 0.05). RESULTS: There was no significant (p > 0.05) difference in frequencies of matched shades for each group at the three sites; except bilayered lithium disilicate crowns. Bilayered lithium disilicate crowns had significantly (p < 0.05) higher match frequency than monolithic zirconia at the middle third. The ΔE value was not significantly (p > 0.05) different among the groups at the cervical third. However, monolithic zirconia had significantly (p < 0.05) higher ΔE values than bilayered lithium disilicate and zirconia at the incisal and middle thirds. CONCLUSIONS: Bilayered lithium disilicate and zirconia appeared to most closely match the shade of an existing bilayered lithium disilicate crown.

Protein-Labeling Fluorescent Probe for Folate Receptor α.

GPI-anchored folate receptor α (FRα) is an attractive anticancer drug target and diagnosis marker in fundamental biology and medical research due to its significant expression on many cancer cells. Currently, analyses of FRα expression levels are usually achieved using immunological methods. Due to the continual FRα synthesis and degradation, immunological methods are not suitable for studying real-time dynamic activities of FRα in living cells. In this paper, we introduce a rapid and specific FRα protein-labeling fluorescent probe, FR1, to facilitate the study of the dynamics of expression and degradation processes of endogenous FRα in living cells. With this labeling probe, insights on FRα protein lifetime and shedding from the cell surface can be obtained using fluorescence live-cell imaging and electrophoresis techniques. We revealed that FRα undergoes soluble domain release and endocytosis degradation simultaneously. Imaging results showed that most of the membrane FRα are transported to the lysosomes after 2 h of incubation. Furthermore, we also showed that the secretion of a FRα soluble domain into the environment is most likely accomplished by phospholipase. We believe that this protein-labeling approach can be an important tool for analyzing various dynamic processes involving FRα.

Fully automated segmentation and radiomics feature extraction of hypopharyngeal cancer on MRI using deep learning.

OBJECTIVES: To use convolutional neural network for fully automated segmentation and radiomics features extraction of hypopharyngeal cancer (HPC) tumor in MRI. METHODS: MR images were collected from 222 HPC patients, among them 178 patients were used for training, and another 44 patients were recruited for testing. U-Net and DeepLab V3 + architectures were used for training the models. The model performance was evaluated using the dice similarity coefficient (DSC), Jaccard index, and average surface distance. The reliability of radiomics parameters of the tumor extracted by the models was assessed using intraclass correlation coefficient (ICC). RESULTS: The predicted tumor volumes by DeepLab V3 + model and U-Net model were highly correlated with those delineated manually (p < 0.001). The DSC of DeepLab V3 + model was significantly higher than that of U-Net model (0.77 vs 0.75, p < 0.05), particularly in those small tumor volumes of < 10 cm3 (0.74 vs 0.70, p < 0.001). For radiomics extraction of the first-order features, both models exhibited high agreement (ICC: 0.71-0.91) with manual delineation. The radiomics extracted by DeepLab V3 + model had significantly higher ICCs than those extracted by U-Net model for 7 of 19 first-order features and for 8 of 17 shape-based features (p < 0.05). CONCLUSION: Both DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images, whereas DeepLab V3 + had a better performance than U-Net. CLINICAL RELEVANCE STATEMENT: The deep learning model, DeepLab V3 + , exhibited promising performance in automated tumor segmentation and radiomics extraction for hypopharyngeal cancer on MRI. This approach holds great potential for enhancing the radiotherapy workflow and facilitating prediction of treatment outcomes. KEY POINTS: • DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images. • DeepLab V3 + model was more accurate than U-Net in automated segmentation, especially on small tumors. • DeepLab V3 + exhibited higher agreement for about half of the first-order and shape-based radiomics features than U-Net.

Protective Effect of Vaccine Doses and Antibody Titers Against SARS-CoV-2 Infection in Kidney Transplant Recipients.

Patients undergoing kidney transplantation have a poor response to vaccination and a higher risk of disease progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of vaccine doses and antibody titer tests against the mutant variant in these patients remains unclear. We retrospectively analyzed the risk of SARS-CoV-2 infection in a single medical center according to vaccine doses and immune responses before the outbreak. Among 622 kidney transplant patients, there were 77 patients without vaccination, 26 with one dose, 74 with two doses, 357 with three, and 88 with four doses. The vaccination status and infection rate proportion were similar to the general population. Patients undergoing more than three vaccinations had a lower risk of infection (odds ratio = 0.6527, 95% CI = 0.4324-0.9937) and hospitalization (odds ratio = 0.3161, 95% CI = 0.1311-0.7464). Antibody and cellular responses were measured in 181 patients after vaccination. Anti-spike protein antibody titer of more than 1,689.3 BAU/mL is protective against SARS-CoV-2 infection (odds ratio = 0.4136, 95% CI = 0.1800-0.9043). A cellular response by interferon-γ release assay was not correlated with the disease (odds ratio = 1.001, 95% CI = 0.9995-1.002). In conclusion, despite mutant strain, more than three doses of the first-generation vaccine and high antibody titers provided better protection against the omicron variant for a kidney transplant recipient.

Prenatal exposure to phthalates and polybrominated diphenyl ethers on neonatal health: A birth cohort study in Guangxi, China.

Few epidemiological studies have focused on prenatal phthalates (PAEs) and polybrominated diphenyl ethers (PBDEs) exposure to neonatal health in China. This study aimed to assess the associations between prenatal PAEs and PBDEs exposure and neonatal health in Guangxi, a Zhuang autonomous region of China. Concentrations of 4 PAEs metabolites (mPAEs) and 5 PBDEs congeners were measured in the serum of 267 healthy pregnant women. Birth outcomes and clinical data of neonates were collected after delivery. Mono-(2-Ethylhexyl) phthalate (MEHP) (81.52%) and BDE47 (35.21%) were the mPAEs and PBDEs congeners with the highest detection rate in serum. Prenatal exposures to mono-n-butyl phthalate (MBP), MEHP, and ΣmPAEs were negatively associated with birth weight (BW), birth length (BL), and gestational age (GA). Higher exposures to MBP, MEHP, and ΣmPAEs were associated with an increased odds ratio (OR) for low birth weight (LBW), but exposure to BDE28 exhibited the opposite effect. Moreover, higher exposures to MBP, MEHP, ΣmPAEs, BDE99, and ΣPBDEswere associated with an increased OR for premature birth (PTB) (P < 0.05). In contrast to MBP exposure, BDE28 exposure was associated with a higher OR for neonatal jaundice (NNJ) (P < 0.05). The interaction analysis showed a positive interaction between monoethyl phthalate (MEP) and BDE28 on the risk of NNJ and positive interaction between ΣmPAEs and BDE47 on the risk of NNJ. In addition, there are ethnicity-specific associations of prenatal PBDEs exposure with neonatal health in individuals of Zhuang and Han nationalities, and boy neonates were more sensitive to prenatal PBDEs exposure than girl neonates. The results revealed that prenatal exposure to mPAEs and PBDEs might have adverse effects on neonatal development, and the effects might be ethnicity- and sex-specific.

Fully automated film mounting in dental radiography: a deep learning model.

BACKGROUND: Dental film mounting is an essential but time-consuming task in dental radiography, with manual methods often prone to errors. This study aims to develop a deep learning (DL) model for accurate automated classification and mounting of both intraoral and extraoral dental radiography. METHOD: The present study employed a total of 22,334 intraoral images and 1,035 extraoral images to train the model. The performance of the model was tested on an independent internal dataset and two external datasets from different institutes. Images were categorized into 32 tooth areas. The VGG-16, ResNet-18, and ResNet-101 architectures were used for pretraining, with the ResNet-101 ultimately being chosen as the final trained model. The model's performance was evaluated using metrics of accuracy, precision, recall, and F1 score. Additionally, we evaluated the influence of misalignment on the model's accuracy and time efficiency. RESULTS: The ResNet-101 model outperformed VGG-16 and ResNet-18 models, achieving the highest accuracy of 0.976, precision of 0.969, recall of 0.984, and F1-score of 0.977 (p < 0.05). For intraoral images, the overall accuracy remained consistent across both internal and external datasets, ranging from 0.963 to 0.972, without significant differences (p = 0.348). For extraoral images, the accuracy consistently achieved the highest value of 1 across all institutes. The model's accuracy decreased as the tilt angle of the X-ray film increased. The model achieved the highest accuracy of 0.981 with correctly aligned films, while the lowest accuracy of 0.937 was observed for films exhibiting severe misalignment of ± 15° (p < 0.001). The average time required for the tasks of image rotation and classification for each image was 0.17 s, which was significantly faster than that of the manual process, which required 1.2 s (p < 0.001). CONCLUSION: This study demonstrated the potential of DL-based models in automating dental film mounting with high accuracy and efficiency. The proper alignment of X-ray films is crucial for accurate classification by the model.

Prevalence of skin diseases in Taiwan prisons: a population-based study.

BACKGROUND: The prevalence of skin diseases among prisoners in Taiwan has rarely been investigated. This study aimed to estimate the prevalence of skin diseases by sex in a sample of prisoners in Taiwan. METHODS: We included 83,048 participants from the National Health Insurance Program. The outcomes were measured using the clinical version of the International Classification of Diseases, Ninth Revision. For prevalence, we presented absolute values as well as percentages. We also conducted an X2 test to assess sex differences and age group differences in the percentages of skin and subcutaneous tissue diseases. RESULTS: The prevalence of skin diseases was 42.25%, higher than that in the general population. The prevalence of skin diseases among male prisoners was higher than that among female prisoners (p < 0.001), and the prevalence of skin diseases among prisoners who were ≤ 40 was higher than that among prisoners who were > 40. Among all cases diagnosed with skin disease, the top three diseases were contact dermatitis and other types of eczema, cellulitis and abscess, pruritus, and related conditions. Male prisoners had a significantly higher prevalence of all types of skin diseases than female prisoners. CONCLUSIONS: Skin diseases are common in prisoners in Taiwan. Therefore, early prevention and appropriate treatment are needed. Male-specific skin products are also needed, given the differences in the prevalence of skin diseases among male and female prisoners.

Cyclodextrin-Mediated Cholesterol Depletion Induces Adiponectin Secretion in 3T3-L1 Adipocytes.

Adipocytes store a significant amount of cholesterol and triglycerides. However, whether cholesterol modulates adipocyte function remains largely unknown. We modulated the cholesterol level in adipocytes to examine its effect on the secretion of adiponectin, an important hormone specifically secreted by adipocytes. Treating differentiated 3T3-L1 adipocytes with 4 mM methyl-ß-cyclodextrin (MßCD), a molecule with a high affinity for cholesterol, rapidly depleted cholesterol in adipocytes. Interestingly, MßCD treatment increased adiponectin in the medium without affecting its intracellular level, suggesting a modulation of secretion. By contrast, cholesterol addition did not affect adiponectin secretion, suggesting that cholesterol-depletion-induced intracellular cholesterol trafficking, but not reduced cholesterol level, accounted for MßCD-induced adiponectin secretion. MßCD-induced adiponectin secretion was reduced after 10 µg/mL U18666A treatment that suppressed cholesterol transport out of late endosomes/lysosomes. Depleting Niemann-Pick type C1 (NPC1) or NPC2 proteins, which mediate endosomal/lysosomal cholesterol export, consistently reduced MßCD-induced adiponectin secretion. Furthermore, treatment with 1 µM bafilomycin A1, which neutralized acidic endosomes/lysosomes, also attenuated MßCD-induced adiponectin secretion. Finally, MßCD treatment redistributed cellular adiponectin to lower-density fractions in sucrose gradient fractionation. Our results show that MßCD-mediated cholesterol depletion elevates the secretion of adiponectin, highlighting the involvement of endosomes and lysosomes in adiponectin secretion in adipocytes.

PIP3 depletion rescues myoblast fusion defects in human rhabdomyosarcoma cells.

Myoblast fusion is required for myotube formation during myogenesis, and defects in myoblast differentiation and fusion have been implicated in a number of diseases, including human rhabdomyosarcoma. Although transcriptional regulation of the myogenic program has been studied extensively, the mechanisms controlling myoblast fusion remain largely unknown. This study identified and characterized the dynamics of a distinct class of blebs, termed bubbling blebs, which are smaller than those that participate in migration. The formation of these bubbling blebs occurred during differentiation and decreased alongside a decline in phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) at the plasma membrane before myoblast fusion. In a human rhabdomyosarcoma-derived (RD) cell line that exhibits strong blebbing dynamics and myoblast fusion defects, PIP3 was constitutively abundant on the membrane during myogenesis. Targeting phosphatase and tensin homolog (PTEN) to the plasma membrane reduced PIP3 levels, inhibited bubbling blebs and rescued myoblast fusion defects in RD cells. These findings highlight the differential distribution and crucial role of PIP3 during myoblast fusion and reveal a novel mechanism underlying myogenesis defects in human rhabdomyosarcoma.

Clinical impact of a deep learning system for automated detection of missed pulmonary nodules on routine body computed tomography including the chest region.

OBJECTIVES: To evaluate the clinical impact of a deep learning system (DLS) for automated detection of pulmonary nodules on computed tomography (CT) images as a second reader. METHODS: This single-centre retrospective study screened 21,150 consecutive body CT studies from September 2018 to February 2019. Pulmonary nodules detected by the DLS on axial CT images but not mentioned in initial radiology reports were flagged. Flagged images were scored by four board-certificated radiologists each with at least 5 years of experience. Nodules with scores of 2 (understandable miss) or 3 (should not be missed) were then categorised as unlikely to be clinically significant (2a or 3a) or likely to be clinically significant (2b or 3b) according to the 2017 Fleischner guidelines for pulmonary nodules. The miss rate was defined as the total number of studies receiving scores of 2 or 3 divided by total screened studies. RESULTS: Among 172 nodules flagged by the DLS, 60 (35%) missed nodules were confirmed by the radiologists. The nodules were further categorised as 2a, 2b, 3a, and 3b in 24, 14, 10, and 12 studies, respectively, with an overall positive predictive value of 35%. Missed pulmonary nodules were identified in 0.3% of all CT images, and one-third of these lesions were considered clinically significant. CONCLUSIONS: Use of DLS-assisted automated detection as a second reader can identify missed pulmonary nodules, some of which may be clinically significant. CLINICAL RELEVANCE/APPLICATION: Use of DLS to help radiologists detect pulmonary lesions may improve patient care. KEY POINTS: • DLS-assisted automated detection as a second reader is feasible in a large consecutive cohort. • Performance of combined radiologists and DLS was better than DLS or radiologists alone. • Pulmonary nodules were missed more frequently in abdomino-pelvis CT than the thoracic CT.

The Power of Women: Does increasing women's parliamentary representation reduce intake of sugar-sweetened beverages among children and adolescents?

OBJECTIVE: Consumption of sugar-sweetened beverages (SSBs) is associated with overweight and obesity in children and adolescents. Although existing research confirms the significance of economic and social factors as determinants of SSB intake, comparative studies on political factors and cross-national analyses are lacking. Research indicates that including women in the process of political decision-making promotes healthcare and child protection. This study examined how women's parliamentary representation influences children's and adolescents' SSB intake compared to adults. DESIGN: The study used cross-national food and beverage intake data from the Global Dietary Database. The outcome measurement was SSB consumption (g/day) for different population groups. We modeled SSB intake as a function of age groups, women's parliamentary representation at the national level (the independent variable), regime types (the contextual factor), and import tariffs on SSBs (the mediator) using country and time fixed effects regression models. SETTING: 185 countries across three waves from 2005 to 2015. PARTICIPANTS: Different population groups. RESULTS: The impact of female representation on reducing SSB consumption is more prevalent in children and adolescents than in adults. Furthermore, the effect of women's parliamentary representation on SSB consumption among children and adolescents is conditional on a country's democratic status. Finally, the marginal effect decreases when import tariffs on SSBs are considered a link in a causal chain. No changes in adult SSB intake are statistically significant. CONCLUSIONS: The findings suggest that the presence of women in the legislature can have a substantial impact on child and adolescent health.