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.

Staphylococcus hsinchuensis sp. nov., Isolated from Soymilk.

A novel coagulase-negative Staphylococcus strain (H164T) was isolated from soymilk in Taiwan. Comparative sequence analysis of the 16S rRNA gene revealed that the H164T strain is a member of the genus Staphylococcus. We used multilocus sequence analysis (MLSA) and phylogenomic analyses to demonstrate that the novel strain was closely related to Staphylococcus gallinarum, Staphylococcus nepalensis, Staphylococcus cohnii, and Staphylococcus urealyuticus. The average nucleotide identity and digital DNA-DNA hybridization values between H164T and its closest relatives were <95% and <70%, respectively. The H164T strain could also be distinguished from its closest relatives by the fermentation of d-fructose, d-maltose, d-trehalose, and d-mannitol, as well as by the activities of α-glucosidase and alkaline phosphatase. The major cellular fatty acids were C15:0 iso and C15:0 anteiso, and the predominant menaquinones were MK-7 and MK-8, respectively. The major cellular fatty acids and predominant menaquinones were C15:0 iso and C15:0 anteiso and MK-7 and MK-8, respectively. In conclusion, this strain represents a novel species, named Staphylococcus hsinchuensis sp. nov., with the type strain H164T (=BCRC 81404T = NBRC 116174T).

The emerging tools for precisely manipulating microtubules.

Cells generate a highly diverse microtubule network to carry out different activities. This network is comprised of distinct tubulin isotypes, tubulins with different post-translational modifications, and many microtubule-based structures. Defects in this complex system cause numerous human disorders. However, how different microtubule subtypes in this network regulate cellular architectures and activities remains largely unexplored. Emerging tools such as photosensitive pharmaceuticals, chemogenetics, and optogenetics enable the spatiotemporal manipulation of structures, dynamics, post-translational modifications, and cross-linking with actin filaments in target microtubule subtypes. This review summarizes the design rationale and applications of these new approaches and aims to provide a roadmap for researchers navigating the intricacies of microtubule dynamics and their post-translational modifications in cellular contexts, thereby opening new avenues for therapeutic interventions.

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

A High Copper Concentration Copper-Quadrol Complex Electroless Solution for Chip Bonding Applications.

This article presents a novel bonding method for chip packaging applications in the semiconductor industry, with a focus on downsizing high-density and 3D-stacked interconnections to improve efficiency and performance. Microfluidic electroless interconnections have been identified as a potential solution for bonding pillar joints at low temperatures and pressures. However, the complex and time-consuming nature of their production process hinders their suitability for mass production. To overcome these challenges, we propose a tailored plating solution using an enhanced copper concentration and plating rate. By eliminating the need for fluid motion and reducing the process time, this method can be used for mass production. The Taguchi approach is first used to optimize the copper-quadrol complex solution with the plating rate and decomposition time. This solution exhibits a copper concentration that is over five times higher than that of conventional solutions, a plating rate of 22.2 µm/h, and a decomposition time of 8 min on a Cu layer substrate. This technique enables Cu pillars to be successfully bonded within 7 min at 35 °C. Planarizing the pillar surface yields a high bonding percentage of 99%. Mechanical shear testing shows a significant fracture strength of 76 MPa.

Impact of Residential Area Characteristics and Political Group Participation on Depression Among Middle-Aged and Older Adults: Results of an 11-Year Longitudinal Study.

Background and Objectives: The claim that political group attendance is associated with poor mental health among older adults may be conditioned on geographic conditions. This study examined the geographical context in which political group participation may be associated with depression. Research Design and Methods: The 11-year follow-up data from the Taiwan Longitudinal Study on Aging, covering 5,334 persons aged ≥50 years, were analyzed using random-effects panel logit models. Depression was assessed using 10 items on the Centre for Epidemiologic Studies Depression scale. Participants were asked to indicate whether they belonged to different social groups. We modeled depression as a function of political group participation (the independent variable) and geographical region (moderators), adjusting for individual-level characteristics. Results: Respondents in political groups were more likely to report depression than those in nonpolitical groups (adjusted odds ratio [AOR] = 1.90, 95% confidence interval [CI] = 1.34-2.68). Between urban and rural settlements, there were no statistically significant differences in mental health outcomes among older adults engaged in political groups (AOR = 1.72, 95% CI = 0.81-3.67). For those who remained politically engaged, living in areas with lower levels of electoral competition was associated with a lower likelihood of depression (AOR = 0.92, 95% CI = 0.86-0.98); this conditional effect was not prevalent among those who were solely engaged in nonpolitical groups (AOR = 1.02, 95% CI = 0.99-1.03). Discussion and Implications: Political group participation is associated with poor mental health among older adults living in politically competitive regions.

Dietary Sodium Restriction and Frailty among Middle-Aged and Older Adults: An 8-Year Longitudinal Study.

Frailty is a common geriatric syndrome. However, there is little information about the relationship between dietary sodium restriction (DSR) and frailty in later life. This study aimed to elucidate the relationship between DSR and frailty in middle-aged and older adults. The 8-year follow-up data from the Taiwan Longitudinal Study on Aging, including 5131 individuals aged ≥50 years, were analyzed using random-effects panel logit models. DSR was evaluated by assessing whether the participants were told by a physician to reduce or avoid sodium intake from food. Three indices were used to measure frailty: the Study of Osteoporotic Fractures (SOF) index, the Fried index, and the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) index. Individuals with DSR were more likely to report frailty compared with those with non-DSR (SOF: adjusted odds ratio [AOR] = 1.82, 95% confidence interval [CI] = 1.46-2.27; Fried: AOR = 2.55, 95% CI = 1.64-3.98; FRAIL: AOR = 2.66, 95% CI = 1.89-3.74). DSR was associated with a higher likelihood of SBF (AOR = 2.61, 95% CI = 1.61-4.22). We identified a temporal trajectory in our study, noting significant participant reactions to both short- and mid-term DSR. Future research should address the balance between frailty risk and cardiovascular risk related to DSR.

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.

Improved capacitive performances and electrocatalytic reduction activity by regulating the bonding interaction between Zn-bistriazole-pyrazine/pyridine units and diverse Anderson-type polyoxometalates.

Electrochemical performances can be effectively improved by introducing metal-organic units (MOUs) into polyoxometalates (POMs). However, regulating the bonding strength between POMs and MOUs at the molecular level to improve the electrochemical performance is a challenging task. Three new POM-based metal-organic complexes (MOCs), namely H{Zn2(Hpytty)2(H2O)8[CrMo6(OH)6O18]}·2H2O (1), H{Zn2(Hpyttz)2(H2O)6[CrMo6(OH)6O18]}·8H2O (2), and {(µ2-OH)2Zn6(pyttz)2(H2O)10[TeMo6O24]}·2H2O (3) (H2pytty = 3-(pyrazin-2-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl, H2pyttz = 3-(pyrid-2-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl), were obtained. Single-crystal X-ray diffraction shows that the bonding strength (from the hydrogen bond to the coordination bond) between Zn-bistriazole-pyrazine/pyridine units and diverse Anderson-type POMs gradually increases from complexes 1 to 3. Glassy carbon electrodes modified with complex 3 (3-GCE) has the highest specific capacitance, which is 930 F g-1 at 1 A g-1. Moreover, carbon paste electrodes (1-3-CPEs) modified with complexes 1-3 are used as electrochemical sensors for detecting Cr(VI) ions, with limits of detection well below the World Health Organization (WHO) maximum level in drinking water.

Interventing mitochondrial PD-L1 suppressed IFN-γ-induced cancer stemness in hepatocellular carcinoma by sensitizing sorafenib-induced ferroptosis.

Evidence recently showed that pleiotropic cytokine interferon-gamma (IFN-γ) in the tumor microenvironment (TME) plays a positive role in hepatocellular carcinoma (HCC) progression through the regulation of liver cancer stem cells (LCSCs) in HCC. The present study explored the role and potential mechanism of mitochondrial programmed cell death-ligand 1 (PD-L1) and its regulation of ferroptosis in modulating the cancer stemness of LCSCs. It was shown that mimicking TME IFN-γ exposure increased the LCSCs ratio and cancer stemness phenotypes in HCC cells. IFN-γ exposure inhibited sorafenib (Sora)-induced ferroptosis by enhancing glutathione peroxidase 4 (GPX4) expression as well reactive oxygen species (ROS) and lipid peroxidation (LPO) generation in LCSCs. Furthermore, IFN-γ exposure upregulated PD-L1 expression and its mitochondrial translocation, inducing dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and correlating with glycolytic metabolism reprogramming in LCSCs. The genetic intervention of PD-L1 promoted ferroptosis-dependent anti-tumor effects of Sora, reduced glycolytic metabolism reprogramming, and inhibited cancer stemness of HCC in vitro and in vivo. Our results revealed a novel mechanism that IFN-γ exposure-induced mitochondrial translocation of PD-L1 enhanced glycolytic reprogramming to mediate the GPX4-dependent ferroptosis resistance and cancer stemness in LCSCs. This study provided new insights into the role of mitochondrial PD-L1-Drp1-GPX4 signal axis in regulating IFN-γ exposure-associated cancer stemness in LCSCs and verified that PD-L1-targeted intervention in combination with Sora might achieve promising synergistic anti-HCC effects.

Machine Learning Radiomics Signature for Differentiating Lymphoma versus Benign Splenomegaly on CT.

BACKGROUND: We aimed to develop and validate a preoperative CT-based radiomics signature for differentiating lymphoma versus benign splenomegaly. METHODS: We retrospectively analyzed CT studies from 139 patients (age range 26-93 years, 43% female) between 2011 and 2019 with histopathological diagnosis of the spleen (19 lymphoma, 120 benign) and divided them into developing (n = 79) and testing (n = 60) datasets. The volumetric radiomic features were extracted from manual segmentation of the whole spleen on venous-phase CT imaging using PyRadiomics package. LASSO regression was applied for feature selection and development of the radiomic signature, which was interrogated with the complete blood cell count and differential count. All p values < 0.05 were considered to be significant. RESULTS: Seven features were selected for constructing the radiomic signature after feature selection, including first-order statistics (10th percentile and Robust Mean Absolute Deviation), shape-based (Surface Area), and texture features (Correlation, MCC, Small Area Low Gray-level Emphasis and Low Gray-level Zone Emphasis). The radiomic signature achieved an excellent diagnostic accuracy of 97%, sensitivity of 89%, and specificity of 98%, distinguishing lymphoma versus benign splenomegaly in the testing dataset. The radiomic signature significantly correlated with the platelet and segmented neutrophil percentage. CONCLUSIONS: CT-based radiomics signature can be useful in distinguishing lymphoma versus benign splenomegaly and can reflect the changes in underlying blood profiles.

Thermosensation and Temperature Preference: From Molecules to Neuronal Circuits in Drosophila.

Temperature has a significant effect on all physiological processes of animals. Suitable temperatures promote responsiveness, movement, metabolism, growth, and reproduction in animals, whereas extreme temperatures can cause injury or even death. Thus, thermosensation is important for survival in all animals. However, mechanisms regulating thermosensation remain unexplored, mostly because of the complexity of mammalian neural circuits. The fruit fly Drosophila melanogaster achieves a desirable body temperature through ambient temperature fluctuations, sunlight exposure, and behavioral strategies. The availability of extensive genetic tools and resources for studying Drosophila have enabled scientists to unravel the mechanisms underlying their temperature preference. Over the past 20 years, Drosophila has become an ideal model for studying temperature-related genes and circuits. This review provides a comprehensive overview of our current understanding of thermosensation and temperature preference in Drosophila. It encompasses various aspects, such as the mechanisms by which flies sense temperature, the effects of internal and external factors on temperature preference, and the adaptive strategies employed by flies in extreme-temperature environments. Understanding the regulating mechanisms of thermosensation and temperature preference in Drosophila can provide fundamental insights into the underlying molecular and neural mechanisms that control body temperature and temperature-related behavioral changes in other animals.

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.

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.

Impact of dietary sodium restriction on falls among middle-aged and older adults: Results of an 8-year longitudinal study.

AIM: This study aimed to understand the relationship between dietary sodium restriction (DSR) and falling experiences in middle-aged and older adults. METHODS: The 8-year follow-up data from the Taiwan Longitudinal Study on Aging, covering 5131 individuals aged ≥50 years, were analyzed using random-effects panel logit models. Participants were asked to indicate whether they were told by a physician to reduce or avoid sodium intake from food and whether they had had fall experiences during the past year. We modelled falling experiences as a function of DSR (independent variable), involuntary body weight loss and walking difficulty (mediators), and chronic diseases (moderator), adjusting for individual-level characteristics. RESULTS: Individuals with DSR were at a higher risk of falls compared with those with no DSR (adjusted odds ratio [AOR] = 1.30, 95% confidence interval [CI] = 1.11-1.53). This effect was more prevalent in individuals with a history of stroke (AOR = 1.85, 95% CI = 1.19-2.87). Those told to reduce sodium intake by a physician were likely to lose weight involuntarily (AOR = 1.20, 95% CI = 1.05-1.36) and had difficulty walking up two or three flights of stairs alone (AOR = 2.38, 95% CI = 1.73-3.27), which mediated the effect of DSR on increased fall risk (AOR = 1.15, 95% CI = 0.95-1.38). We found a temporal effect: participant reactions to short- and mid-term DSR were significant. CONCLUSIONS: DSR was associated with a greater likelihood of falls among middle-aged and older adults, particularly those with a history of stroke. Geriatr Gerontol Int 2023; ••: ••-••.

Mesenchymal Stem Cell-Derived Exosomes Mitigate Acute Murine Liver Injury via Ets-1 and Heme Oxygenase-1 Up-regulation.

BACKGROUND: Mesenchymal stem cells (MSCs)-derived exosomes have been previously demonstrated to promote tissue regeneration in various animal disease models. This study investigated the protective effect of exosome treatment in carbon tetrachloride (CCl4)-induced acute liver injury and delineated possible underlying mechanism. METHODS: Exosomes collected from conditioned media of previously characterized human umbilical cord-derived MSCs were intraperitoneally administered into male CD-1 mice with CCl4-induced acute liver injury. Biochemical, histological and molecular parameters were used to evaluate the severity of liver injury. A rat hepatocyte cell line, Clone-9, was used to validate the molecular changes by exosome treatment. RESULTS: Exosome treatment significantly suppressed plasma levels of AST, ALT, and pro-inflammatory cytokines, including IL-6 and TNF-, in the mice with CCl4-induced acute liver injury. Histological morphometry revealed a significant reduction in the necropoptic area in the injured livers following exosome therapy. Consistently, western blot analysis indicated marked elevations in hepatic expression of PCNA, c-Met, Ets-1, and HO-1 proteins after exosome treatment. Besides, the phosphorylation level of signaling mediator JNK was significantly increased, and that of p38 was restored by exosome therapy. Immunohistochemistry double staining confirmed nuclear Ets-1 expression and cytoplasmic localization of c-Met and HO-1 proteins. In vitro studies demonstrated that exosome treatment increased the proliferation of Clone-9 hepatocytes and protected them from CCl4-induced cytotoxicity. Kinase inhibition experiment indicated that the exosome-driven hepatoprotection might be mediated through the JNK pathway. CONCLUSION: Exosome therapy activates the JNK signaling activation pathway as well as up-regulates Ets-1 and HO-1 expression, thereby protecting hepatocytes against hepatotoxin-induced cell death.

Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Parameters Could Predict International Society of Urological Pathology Risk Groups of Prostate Cancers on Radical Prostatectomy.

BACKGROUND: The International Society of Urological Pathology (ISUP) grade and positive surgical margins (PSMs) after radical prostatectomy (RP) may reflect the prognosis of prostate cancer (PCa) patients. This study aimed to investigate whether DCE-MRI parameters (i.e., Ktrans, kep, and IAUC) could predict ISUP grade and PSMs after RP. METHOD: Forty-five PCa patients underwent preoperative DCE-MRI. The clinical characteristics and DCE-MRI parameters of the 45 patients were compared between the low- and high-risk (i.e., ISUP grades III-V) groups and between patients with or without PSMs after RP. Multivariate logistic regression analysis was used to identify the significant predictors of placement in the high-risk group and PSMs. RESULTS: The DCE parameter Ktrans-max was significantly higher in the high-risk group than in the low-risk group (p = 0.028) and was also a significant predictor of placement in the high-risk group (odds ratio [OR] = 1.032, 95% confidence interval [CI] = 1.005-1.060, p = 0.021). Patients with PSMs had significantly higher prostate-specific antigen (PSA) titers, positive biopsy core percentages, Ktrans-max, kep-median, and kep-max than others (all p < 0.05). Of these, positive biopsy core percentage (OR = 1.035, 95% CI = 1.003-1.068, p = 0.032) and kep-max (OR = 1.078, 95% CI = 1.012-1.148, p = 0.020) were significant predictors of PSMs. CONCLUSION: Preoperative DCE-MRI parameters, specifically Ktrans-max and kep-max, could potentially serve as preoperative imaging biomarkers for postoperative PCa prognosis based on their predictability of PCa risk group and PSM on RP, respectively.

NME3 binds to phosphatidic acid and mediates PLD6-induced mitochondrial tethering.

Mitochondria are dynamic organelles regulated by fission and fusion processes. The fusion of membranes requires elaborative coordination of proteins and lipids and is particularly crucial for the function and quality control of mitochondria. Phosphatidic acid (PA) on the mitochondrial outer membrane generated by PLD6 facilitates the fusion of mitochondria. However, how PA promotes mitochondrial fusion remains unclear. Here, we show that a mitochondrial outer membrane protein, NME3, is required for PLD6-induced mitochondrial tethering or clustering. NME3 is enriched at the contact interface of two closely positioned mitochondria depending on PLD6, and NME3 binds directly to PA-exposed lipid packing defects via its N-terminal amphipathic helix. The PA binding function and hexamerization confer NME3 mitochondrial tethering activity. Importantly, nutrient starvation enhances the enrichment efficiency of NME3 at the mitochondrial contact interface, and the tethering ability of NME3 contributes to fusion efficiency. Together, our findings demonstrate NME3 as a tethering protein promoting selective fusion between PLD6-remodeled mitochondria for quality control.

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.