Perception and response of skeleton to mechanical stress.

Mechanical stress stands as a fundamental factor in the intricate processes governing the growth, development, morphological shaping, and maintenance of skeletal mass. The profound influence of stress in shaping the skeletal framework prompts the assertion that stress essentially births the skeleton. Despite this acknowledgment, the mechanisms by which the skeleton perceives and responds to mechanical stress remain enigmatic. In this comprehensive review, our scrutiny focuses on the structural composition and characteristics of sclerotin, leading us to posit that it serves as the primary structure within the skeleton responsible for bearing and perceiving mechanical stress. Furthermore, we propose that osteocytes within the sclerotin emerge as the principal mechanical-sensitive cells, finely attuned to perceive mechanical stress. And a detailed analysis was conducted on the possible transmission pathways of mechanical stress from the extracellular matrix to the nucleus.

Tracking the effects of PLGA-based nanoparticles on protein expression in living cells through quantitative proteomics.

Mass spectrometry (MS)-based proteomics can identify and quantify the differential abundance of expressed proteins in parallel, and bottom-up proteomic approaches are even approaching comprehensive coverage of the complex eukaryotic proteome. Protein-nanoparticle (NP) interactions have been extensively studied owing to their importance in biological applications and nanotoxicology. However, the proteome-level effects of NPs on cells have received little attention, although changes in protein abundance can reflect the direct effects of nanocarriers on protein expression. Herein, we investigated the effect of PLGA-based NPs on protein expression in HepG2 cells using a label-free quantitative proteomics approach with data independent acquisition (DIA). The percentage of two-fold change in the protein expression of cells treated with PLGA-based NPs was less than 10.15% during a 6 hour observation period. Among the changed proteins, we found that dynamic proteins involved in cell division, localization, and transport are more likely to be more susceptible to PLGA-based NPs.

Cystatin C is a predictor for long-term All-Cause and Cardiovascular Mortality in US Adults with Metabolic Syndrome.

OBJECTIVE: This study examined the relationship between Cystatin C (CysC) levels and all-cause, CVD, and cancer mortality in US metabolic syndrome (MetS) patients. METHODS: The 1999-2002 National Health and Nutrition Examination Survey (NHANES) prospective cohort research included 1,980 MetS participants. To assess CysC levels and all-cause, CVD, and cancer mortality, fitted curves, Kaplan-Meier survival curves, cox regression analysis, and ROC curves were performed. RESULTS: During a mean follow-up of 15.3 ± 5.4 years, a total of 819 deaths occurred. The fitted and Kaplan-Meier survival curves revealed that greater CysC levels were linked to higher all-cause, CVD, and cancer mortality rates (P<0.05). After adjusting for variables, CysC level was associated with all-cause, CVD, and cancer mortality at 1.63 (1.42-1.88), 1.53 (1.19-1.95), and 1.53 (1∼2.32), respectively (P<0.05). Later tertile models showed consistent results. High CysC tertile participants showed higher risk of all-cause mortality (HR 1.87; 1.43-2.45), CVD mortality (HR 1.97, 1.15∼3.38), and cancer mortality (HR 1.72, 1.01∼2.91) compared to those in the lowest tertile (P<0.05). Subgroup studies by sex and other characteristics confirmed the findings. CysC demonstrated the higher predictive efficacy across mortality outcomes, followed by eGFR, outperforming Urea nitrogen, Creatinine, Uric acid, and CRP. CysC alone exhibited substantial predictive value for all-cause (AUC 0.773; P<0.05) and CVD mortality (AUC 0.726; P<0.05). Combining CysC with age enhanced the predictive value for all-cause mortality to 0.861 and CVD mortality to 0.771 (P<0.05). CONCLUSION: MetS patients with elevated CysC levels have a higher risk of all-cause, CVD, and cancer death. CysC may predict MetS all-cause and CVD mortality.

Proteomic analysis reveals that the co-ordination of cytosolic and mitochondrial pathways is beneficial for sabinene biosynthesis in engineered Saccharomyces cerevisiae.

Reconstruction and optimization of biosynthetic pathways can help to overproduce target chemicals in microbial cell factories based on genetic engineering. However, the perturbation of biosynthetic pathways on cellular metabolism is not well investigated and profiling the engineered microbes remains challenging. The rapid development of omics tools has the potential to characterize the engineered microbial cell factory. Here, we performed label-free quantitative proteomic analysis and metabolomic analysis of engineered sabinene overproducing Saccharomyces cerevisiae strains. Combined metabolic analysis andproteomic analysis of targeted mevalonate (MVA) pathway showed that co-ordination of cytosolic and mitochondrial pathways had balanced metabolism, and genome integration of biosynthetic genes had higher sabinene production with less MVA enzymes. Furthermore, comparative proteomic analysis showed that compartmentalized mitochondria pathway had perturbation on central cellular metabolism. This study provided an omics analysis example for characterizing engineered cell factory, which can guide future regulation of the cellular metabolism and maintaining optimal protein expression levels for the synthesis of target products.

Improving water quality and mitigating CH4 and N2O production in urban landscape water simultaneously by optimizing calcium peroxide dosage.

Recent studies show that greenhouse gas (GHG) emissions from urban landscape water are significant and cannot be overlooked, underscoring the need to develop effective strategies for mitigating GHG production from global freshwater systems. Calcium peroxide (CaO2) is commonly used as an eco-friendly reagent for controlling eutrophication in water bodies, but whether CaO2 can reduce GHG emissions remains unclear. This study investigated the effects of CaO2 dosage on the production of methane (CH4) and nitrous oxide (N2O) in urban landscape water under anoxic conditions during summer. The findings reveal that CaO2 addition not only improved the physicochemical and organoleptic properties of simulated urban landscape water but also reduced N2O production by inhibiting the activity of denitrifying bacteria across various dosages. Moreover, CaO2 exhibited selective effects on methanogens. Specifically, the abundance of acetoclastic methanogen Methanosaeta and methylotrophic methanogen Candidatus_Methanofastidiosum increased whereas the abundance of the hydrogenotrophic methanogen Methanoregula decreased at low, medium, and high dosages, leading to higher CH4 production at increased CaO2 dosage. A comprehensive multi-objective evaluation indicated that an optimal dosage of 60 g CaO2/m2 achieved 41.21 % and 84.40 % reductions in CH4 and N2O production, respectively, over a 50-day period compared to the control. This paper not only introduces a novel approach for controlling the production of GHGs, such as CH4 and N2O, from urban landscape water but also suggests a methodology for optimizing CaO2 dosage, providing valuable insights for its practical application.

Comparison of knee joint and temporomandibular joint development in pig embryos.

Although the knee joint (KNJ) and temporomandibular joint (TMJ) all belong to the synovial joint, there are many differences in developmental origin, joint structure and articular cartilage type. Studies of joint development in embryos have been performed, mainly using poultry and rodents. However, KNJ and TMJ in poultry and rodents differ from those in humans in several ways. Very little work has been done on the embryonic development of KNJ and TMJ in large mammals. Several studies have shown that pigs are ideal animals for embryonic development research. Embryonic day 30 (E30), E35, E45, E55, E75, E90, Postnatal day 0 (P0) and Postnatal day 30 (P30) embryos/fetuses from the pigs were used for this study. The results showed that KNJ develops earlier than TMJ. Only one mesenchymal condensate of KNJ is formed on E30, while two mesenchymal condensates of TMJ are present on E35. All structures of KNJ and TMJ were formed on E45. The growth plate of KNJ begins to develop on E45 and becomes more pronounced from E55 to P30. From E75 to E90, more and more vascular-rich cartilage canals form in the cartilage regions of both joints. The cartilaginous canal of the TMJ divides the condyle into sections along the longitudinal axis of the condyle. This arrangement of cartilaginous canal was not found in the KNJ. The chondrification of KNJ precedes that of TMJ. Ossification of the knee condyle occurs gradually from the middle to the periphery, while that of the TMJ occurs gradually from the base of the mandibular condyle. In the KNJ, the ossification of the articular condyle is evident from P0 to P30, and the growth plate is completely formed on P30. In the TMJ, the cartilage layer of condyle becomes thinner from P0 to P30. There is no growth plate formation in TMJ during its entire development. There is no growth plate formation in the TMJ throughout its development. The condyle may be the developmental center of the TMJ. The chondrocytes and hypertrophic chondrocytes of the growth plate are densely arranged. The condylar chondrocytes of TMJ are scattered, while the hypertrophic chondrocytes are arranged. Embryonic development of KNJ and TMJ in pigs is an important bridge for translating the results of rodent studies to medical applications.

Clinical Characteristics of Adrenal Hemangioma.

Objective: Adrenal hemangioma (AH) is a rare, benign adrenal tumor often detected incidentally by imaging. This retrospective study aimed to investigate the clinical characteristics of AH, including clinical and diagnostic imaging features, to improve the recognition and understanding of AH. Methods: We retrospectively analyzed the medical records of patients diagnosed with AH at Peking Union Medical College Hospital between 2008 and 2022. Clinical manifestations, adrenal hormone levels, imaging findings, treatment approaches, and pathological results were collected and analyzed. Results: Of the 7140 adrenal tumor patients, 40 (0.56%) had AH confirmed postoperatively. The mean age at diagnosis was 53.9 years, with a female predominance. Most (70%) were asymptomatic and diagnosed incidentally. Misdiagnosis before surgery was common, most frequently as pheochromocytoma. Imaging characteristics, especially enhanced computed tomography, revealed distinct features based on tumor size. Surgery was the main treatment, with laparoscopic adrenalectomy preferred. Conclusion: This study elucidates the clinical characteristics of AH, including demographics, diagnostic challenges, and imaging features. AH often presents incidentally and is frequently misdiagnosed preoperatively. Recognizing distinct imaging characteristics and appropriate surgical management can enable accurate diagnosis and optimal treatment.

Diet-derived circulating antioxidants and risk of epilepsy: A study combining metabolomics and mendelian randomization.

Background: Previous studies offer inconclusive results on the association between diet-derived circulating antioxidants and epilepsy. Objective: This study aims to assess oxidative stress presence in epilepsy patients' circulation and investigate the causal link between diet-derived circulating antioxidants and epilepsy. Methods: Untargeted metabolomics analysis was conducted on plasma samples from 62 epileptic patients and 20 healthy individuals to evaluate oxidative stress based on metabolite alterations in epilepsy patients' circulation. Two-sample Mendelian Randomization (MR) analysis examined the causation between diet-derived circulating antioxidants (measured by absolute levels and relative metabolite concentrations) and epilepsy, utilizing the inverse-variance weighted (IVW) method as the primary outcome, with complementary MR analysis methods (MR Egger, weighted median, weighted mode, and simple mode). Results: Untargeted metabolomics analysis revealed elevated circulating oxidizing metabolites (palmitic acid, oleic acid, linoleic acid, and myristic acid) and reduced reducing metabolites (glutamine) in epilepsy patients, providing robust evidence of oxidative stress. The IVW analysis indicated significantly reduced epilepsy risk (odds ratio: 0.552; 95% confidence interval: 0.335-0.905, P = 0.018) with genetically determined higher absolute circulating ß-carotene. However, other diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, and selenium) and antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbic acid, and retinol) did not significantly associate with epilepsy risk. Additional MR analysis methods and heterogeneity assessments confirmed the results' robustness. Conclusion: This study provides compelling evidence of oxidative stress in epilepsy patients' circulation. However, the majority of diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, vitamin E, and selenium) are unlikely to causally associate with reduced epilepsy risk, except for ß-carotene.

A Cell-Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome.

Intracellular proteome aggregation is a ubiquitous disease hallmark with its composition associated with pathogenicity. Herein, this work reports on a cell-permeable photosensitizer (P8, Rose Bengal derivative) for selective photo induced proximity labeling and crosslinking of cellular aggregated proteome. Rose Bengal is identified out of common photosensitizer scaffolds for its unique intrinsic binding affinity to various protein aggregates driven by the hydrophobic effect. Further acetylation permeabilizes Rose Bengal to selectively image, label, and crosslink aggregated proteome in live stressed cells. A combination of photo-chemical, tandem mass spectrometry, and protein biochemistry characterizations reveals the complexity in photosensitizing pathways (both Type I & II), modification sites and labeling mechanisms. The diverse labeling sites and reaction types result in highly effective enrichment and identification of aggregated proteome. Finally, aggregated proteomics and interaction analyses thereby reveal extensive entangling of proteostasis network components mediated by HSP70 chaperone (HSPA1B) and active participation of autophagy pathway in combating proteasome inhibition. Overall, this work exemplifies the first photo induced proximity labeling and crosslinking method (namely AggID) to profile intracellular aggregated proteome and analyze its interactions.

Patient-specific factors for deformity after upper blepharoplasty in an Asian population.

BACKGROUND: The success of upper blepharoplasty depends on both surgeon experience and skill as well as patient factors. Therefore, we aimed to identify patient-specific characteristics that may contribute to poor prognoses by analyzing data derived from patients with various deformities after undergoing upper blepharoplasty. METHODS: This study included 202 patients who underwent revision surgery for upper blepharoplasty. We explored relationships between types of deformities before revisions and relevant patient factors before initial surgery using statistical analyses. RESULTS: Age > 30 years, thick upper lid skin, medial epicanthus, and other patient factors were significantly associated with the deformities. Asymmetrical, disappeared, shallow, and low creases were the most prevalent deformities. For these four most prevalent deformities, the concordance indices and 95% confidence limits of the risk prediction models were 0.654 (0.575-0.734), 0.724 (0.637-0.810), 0.783 (0.702-0.863), and 0.750 (0.655-0.844), respectively. CONCLUSIONS: Among the four most prevalent prognostic deformities, significant patient factors included medial epicanthus, thick upper eyelid skin, weak levator palpebrae superioris, age > 30 y, and a short gap between eyes and brows. We also attempted to clarify the clinical importance of these patient factors. Our findings provide a guide and reference for future investigations into upper blepharoplasty.

Liver transcriptome analysis reveal the metabolic and apoptotic responses of Trachinotus ovatus under acute cold stress.

Trachinotus ovatus is an economically important fish and has been recommended as a high-quality aquaculture fish breed for the high-quality development of sea ranches in the South China Sea. However, T. ovatus shows intolerance to low temperature, greatly limiting the extension of farming scale, reducing production efficiency in winter, and increasing farming risks. In this study, liver transcriptome analysis was investigated in T. ovatus under acute low temperature conditions (20 and 15 °C) using RNA sequencing (RNA-Seq) technology. Inter-groups differential expression analysis and trend analysis screened 1219 DEGs and four significant profiles (profiles 0, 3, 4, and 7), respectively. GO enrichment analysis showed that these DEGs were mainly related to metabolic process and cell growth and death process. KEGG enrichment analysis found that DEGs were mainly associated with lipid metabolism, carbohydrate metabolism, and cell growth and death, such as gluconeogenesis, glycolysis, fatty acid oxidation, cholesterol biosynthesis, p53 signaling pathway, cell cycle arrest, and apoptotic cell death. Moreover, protein-protein interaction networks identified two hub genes (FOS and JUNB) and some important genes related to metabolic process and cell growth and death process, that corresponding to enrichment analysis. Overall, gluconeogenesis, lipid mobilization, and fatty acid oxidation in metabolic process and cell cycle arrest and apoptotic cell death in cell growth and death process were enhanced, while glycolysis, liver glycogen synthesis and cholesterol biosynthesis in metabolic process were inhibited. The enhancement or attenuatment of metabolic process and cell growth and death process is conducive to maintain energy balance, normal fluidity of cell membrane, normal physiological functions of liver cell, enhancing the tolerance of T. ovatus to cold stress. These results suggested that metabolic process and cell growth and death process play important roles in response to acute cold stress in the liver of T. ovatus. Gene expreesion level analysis showed that acute cold stress at 15 °C was identified as a critical temperature point for T. ovatus in term of cellular metabolism alteration and apoptosis inducement, and rewarming intervention should be timely implemented above 15 °C. Our study can provide theoretical support for breeding cold-tolerant cultivars of T. ovatus, which is contributed to high-quality productions fish production.

The discrepancy in timing between synchronous signals and visual stimulation should not be underestimated.

Response latency is a critical parameter in studying human behavior, representing the time interval between the onset of stimulus and the response. However, different time between devices can introduce errors. Serial port synchronization signal can mitigate this, but limited information is available regarding their accuracy. Optical signals offer another option, but the difference in the positioning of optical signals and visual stimuli can introduce errors, and there have been limited reports of error reduction. This study aims to investigate methods for reducing the time errors. We used the Psychtoolbox to generate visual stimuli and serial port synchronization signals to explore their accuracy. Subsequently, we proposed a calibration formula to minimize the error between optical signals and visual stimuli. The findings are as follows: Firstly, the serial port synchronization signal presenting precedes visual stimulation, with a smaller lead time observed at higher refresh rates. Secondly, the lead time increases as the stimulus position deviates to the right and downwards. In Linux and IOPort(), serial port synchronization signals exhibited greater accuracy. Considering the poor accuracy and the multiple influencing factors associated with serial port synchronization signals, it is recommended to use optical signals to complete time synchronization. The results indicate that under the darkening process, the time error is - 0.23 ~ 0.08 ms (mean). This calibration formula can help measure the response latency accurately. This study provides valuable insights for optimizing experimental design and improving the accuracy of response latency. Although it only involves visual stimuli, the methods and results of this study can still serve as a reference.

Corydecusines A-H, new phthalideisoquinoline hemicetal alkaloids from the bulbs of Corydalis decumbens inhibit Tau pathology by activating autophagy mediated by AMPK-ULK1 pathway.

Twelve phthalideisoquinoline hemiacetal alkaloids including eight new ones (1-8) and one natural alkaloid characterized by an aziridine moiety with unassigned NMR data (9), were isolated and identified from the bulbs of Corydalis decumbens. Their structures were established by comprehensive analyses of HRESIMS, NMR, X-ray crystallography, and ECD analyses. The unambiguously established structures of the phthalideisoquinoline hemiacetal alkaloids indicated that the absolute configurations of C-1, C-9, and C-7' were confusable only relied on coupling constants. A summary of their ECD spectra was concluded and provided an insight for C-1, C-9, and C-7' absolute configuration assignment. These new compounds were evaluated to induce autophagy flux through flow cytometry analysis. Moreover, compounds 2 and 6 could significantly induce autophagy and inhibit Tau pathology by AMPK-ULK1 pathway activation, which provided an avenue for anti-AD lead compounds discovery.

Nomograms for predicting clinically significant prostate cancer in men with PI-RADS-3 biparametric magnetic resonance imaging.

This study aimed to construct nomograms for predicting the likelihood of clinically significant prostate cancer (csPCa) in patients with lesions rated as Prostate Imaging Reporting and Data System (PI-RADS) 3 on biparametric magnetic resonance imaging (bpMRI). We retrospectively analyzed a cohort of 457 patients from the Peking Union Medical College Hospital (January 2017-July 2021) to develop the model and externally validated it with a cohort of 238 patients from the Second Hospital of Tianjin Medical University (September 2017-September 2021). Univariate and multivariate logistic regression analyses identified significant predictors of csPCa, defined by tumor volumes ≥ 0.5 cm3, Gleason score ≥ 7, or presence of extracapsular extension. Diagnostic performance for the peripheral zone (PZ) and transitional zone (TZ) was compared using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Through univariate and multivariate logistic regression analyses, we identified age, prostate-specific antigen (PSA), and prostate volume (PV) as predictors of csPCa for the PZ, and age, serum-free to total PSA ratio (f/t PSA), and PSA density (PSAD) for the TZ. The nomograms demonstrated robust discriminative ability, with an area under the ROC curve (AUC) of 0.819 for PZ and 0.804 for TZ. The external validation corroborated the model's high predictive accuracy (AUC of 0.831 for PZ and 0.773 for TZ). Calibration curves indicated excellent agreement between predicted and observed outcomes, and DCA underscored the nomogram's clinical utility for both PZ and TZ. Overall, the nomograms offer high predictive accuracy for csPCa at initial biopsy, potentially reducing unnecessary biopsies in clinical settings.

Prospective comparative clinical study: Efficacy evaluation of collagen combined with hyaluronic acid injections for tear trough deformity.

BACKGROUND: Tear trough filling is a popular facial rejuvenation procedure, and hyaluronic acid is typically used as the filler of choice. However, Tyndall's phenomenon, a common complication following hyaluronic acid injection, can occur, leading to skin discoloration of the lower eyelid. AIMS: This single-center, prospective, comparative clinical study aimed to evaluate the efficacy of collagen and hyaluronic acid injections in treating tear trough deformity. METHODS: Sixty patients were enrolled between June 2022 and January 2023. Patients were randomly allocated into three groups: Group A received hyaluronic acid, Group B received hyaluronic acid combined with collagen, and Group C received collagen alone. Baseline characteristics, including age, sex, and tear trough deformity grade were considered before therapy. Changes in tear trough deformity scores, Global Aesthetic Improvement Scores, and the presence of the Tyndall effect were analyzed at 1 and 3 months postinjection to determine differences among the three groups. RESULTS: Baseline profiles of the three groups were similar. In the first month postinjection, there was no difference in the Global Aesthetic Improvement Scores and tear trough deformity between the three groups. However, in the third-month postinjection, there was a significant difference in scores between patients in Group C and those in Groups A or B. The Tyndall effect manifested in three patients in Group A, which was significantly different from that in Groups B and C. CONCLUSION: The combined use of hyaluronic acid with collagen in injectable fillers corrected tear trough deformities and reduced the occurrence of the Tyndall phenomenon, which can be problematic with hyaluronic acid alone. Additionally, this combination may help overcome the disadvantage of a shorter retention period when using collagen alone.

Magnesium Depletion Score and Metabolic Syndrome in US Adults: Analysis of NHANES 2003-2018.

BACKGROUND: The association between magnesium status and metabolic syndrome remains unclear. This study aimed to examine the relationship between the kidney reabsorption-related magnesium depletion score (MDS) and metabolic syndrome among US adults. METHODS: We analyzed data from 15,565 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III report. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. Weighted univariate and multivariate logistic regression were used to assess the association between MDS and metabolic syndrome. Restricted cubic spline analysis was conducted to characterize dose-response relationships. Stratified analyses by sociodemographic and lifestyle factors were also performed. RESULTS: In both univariate and multivariate analyses, higher MDS was significantly associated with increased odds of metabolic syndrome. Each unit increase in MDS was associated with approximately a 30% higher risk for metabolic syndrome, even after adjusting for confounding factors (OR 1.31; 95% CI 1.17-1.45). Restricted cubic spline graphs depicted a linear dose-response relationship across the MDS range. This positive correlation remained consistent across various population subgroups and exhibited no significant interaction by age, gender, race, adiposity, smoking status, or alcohol consumption. CONCLUSIONS: Higher urinary magnesium loss as quantified by MDS may be an independent linear risk factor for metabolic syndrome in US adults, irrespective of sociodemographic and behavioral factors. Optimizing magnesium nutritional status could potentially confer benefits to patients with metabolic syndrome.

Explorations of using a convolutional neural network to understand brain activations during movie watching.

Neuroimaging studies increasingly use naturalistic stimuli like video clips to trigger complex brain activations, but the complexity of such stimuli makes it difficult to assign specific functions to the resulting brain activations, particularly for higher-level content like social interactions. To address this challenge, researchers have turned to deep neural networks, e.g., convolutional neural networks (CNNs). CNNs have shown success in image recognition due to their different levels of features enabling high performance. In this study, we used pre-trained VGG-16, a popular CNN model, to analyze video data and extract hierarchical features from low-level shallow layers to high-level deeper layers, linking these activations to different levels of activation of the human brain. We hypothesized that activations in different layers of VGG-16 would be associated with different levels of brain activation and visual processing hierarchy in the brain. We were also curious about which brain regions would be associated with deeper convolutional layers in VGG-16. The study analyzed a functional MRI (fMRI) dataset where participants watched the cartoon movie Partly Cloudy. Frames of the videos were fed into VGG-16, and activation maps from different kernels and layers were extracted. Time series of the average activation patterns for each kernel were created and fed into a voxel-wise model to study brain activations. Results showed that lower convolutional layers (1st convolutional layer) were mostly associated with lower visual regions, but some kernels (6, 19, 24, 42, 55, and 58) surprisingly showed associations with activations in the posterior cingulate cortex, part of the default mode network. Deeper convolutional layers were associated with more anterior and lateral portions of the visual cortex (e.g., the lateral occipital complex) and the supramarginal gyrus. Analyzing activation features associated with different brain regions showed the promise and limitations of using CNNs to link video content to brain functions.

Whole-Genome Sequencing Analyses Reveal the Whip-like Tail Formation, Innate Immune Evolution, and DNA Repair Mechanisms of Eupleurogrammus muticus.

Smallhead hairtail (Eupleurogrammus muticus) is an important marine economic fish distributed along the northern Indian Ocean and the northwest Pacific coast; however, little is known about the mechanism of its genetic evolution. This study generated the first genome assembly of E. muticus at the chromosomal level using a combination of PacBio SMRT, Illumina Nova-Seq, and Hi-C technologies. The final assembled genome size was 709.27 Mb, with a contig N50 of 25.07 Mb, GC content of 40.81%, heterozygosity rate of 1.18%, and repetitive sequence rate of 35.43%. E. muticus genome contained 21,949 protein-coding genes (97.92% of the genes were functionally annotated) and 24 chromosomes. There were 143 expansion gene families, 708 contraction gene families, and 4888 positively selected genes in the genome. Based on the comparative genomic analyses, we screened several candidate genes and pathways related to whip-like tail formation, innate immunity, and DNA repair in E. muticus. These findings preliminarily reveal some molecular evolutionary mechanisms of E. muticus at the genomic level and provide important reference genomic data for the genetic studies of other trichiurids.

Histone FRET reports the spatial heterogeneity in nanoscale chromatin architecture that is imparted by the epigenetic landscape at the level of single foci in an intact cell nucleus.

Genome sequencing has identified hundreds of histone post-translational modifications (PTMs) that define an open or compact chromatin nanostructure at the level of nucleosome proximity, and therefore serve as activators or repressors of gene expression. Direct observation of this epigenetic mode of transcriptional regulation in an intact single nucleus, is however, a complex task. This is because despite the development of fluorescent probes that enable observation of specific histone PTMs and chromatin density, the changes in nucleosome proximity regulating gene expression occur on a spatial scale well below the diffraction limit of optical microscopy. In recent work, to address this research gap, we demonstrated that the phasor approach to fluorescence lifetime imaging microscopy (FLIM) of Förster resonance energy transfer (FRET) between fluorescently labelled histones core to the nucleosome, is a readout of chromatin nanostructure that can be multiplexed with immunofluorescence (IF) against specific histone PTMs. Here from application of this methodology to gold standard gene activators (H3K4Me3 and H3K9Ac) versus repressors (e.g., H3K9Me3 and H3K27Me), we find that while on average these histone marks do impart an open versus compact chromatin nanostructure, at the level of single chromatin foci, there is significant spatial heterogeneity. Collectively this study illustrates the importance of studying the epigenetic landscape as a function of space within intact nuclear architecture and opens the door for the study of chromatin foci sub-populations defined by combinations of histone marks, as is seen in the context of bivalent chromatin.