CLOCK Acetylates ASS1 to Drive Circadian Rhythm of Ureagenesis.

In addition to responding to environmental entrainment with diurnal variation, metabolism is also tightly controlled by cell-autonomous circadian clock. Extensive studies have revealed key roles of transcription in circadian control. Post-transcriptional regulation for the rhythmic gating of metabolic enzymes remains elusive. Here, we show that arginine biosynthesis and subsequent ureagenesis are collectively regulated by CLOCK (circadian locomotor output cycles kaput) in circadian rhythms. Facilitated by BMAL1 (brain and muscle Arnt-like protein), CLOCK directly acetylates K165 and K176 of argininosuccinate synthase (ASS1) to inactivate ASS1, which catalyzes the rate-limiting step of arginine biosynthesis. ASS1 acetylation by CLOCK exhibits circadian oscillation in human cells and mouse liver, possibly caused by rhythmic interaction between CLOCK and ASS1, leading to the circadian regulation of ASS1 and ureagenesis. Furthermore, we also identified NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 (NDUFA9) and inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) as acetylation substrates of CLOCK. Taken together, CLOCK modulates metabolic rhythmicity by acting as a rhythmic acetyl-transferase for metabolic enzymes.

Phosphoric Acid-Catalyzed Alkene Difunctionalization of 2-Vinylpyridines via HOMO/LUMO Biactivated Diels-Alder Reaction.

The difunctionalization of vinylpyridines based on the cyclization strategy remains rare and underdeveloped, in contrast to the well-developed hydrogen functionalization. Current exploration on [4 + 2] cyclization of vinylpyridines mainly relies on extremely high temperatures and the LUMO activation of vinylpyridines using boron trifluoride as a strong Lewis acid. Herein, we established a phosphoric acid-catalyzed [4 + 2] cyclization reaction of 3-vinyl-1H-indoles and 2-vinylpyridines by means of the LUMO/HOMO bifunctional activation model. This protocol features mild reaction conditions, high functional group tolerance, broad substrate compatibility, and high diastereoselectivity, enabling the efficient construction of various functionalized pyridine-substituted tetrahydrocarbazoles with prominent potential in drug discovery.

Potent inhibitors targeting cyclin-dependent kinase 9 discovered via virtual high-throughput screening and absolute binding free energy calculations.

Due to the crucial regulatory mechanism of cyclin-dependent kinase 9 (CDK9) in mRNA transcription, the development of kinase inhibitors targeting CDK9 holds promise as a potential treatment strategy for cancer. A structure-based virtual screening approach has been employed for the discovery of potential novel CDK9 inhibitors. First, compounds with kinase inhibitor characteristics were identified from the ZINC15 database via virtual high-throughput screening. Next, the predicted binding modes were optimized by molecular dynamics simulations, followed by precise estimation of binding affinities using absolute binding free energy calculations based on the free energy perturbation scheme. The binding mode of molecule 006 underwent an inward-to-outward flipping, and the new binding mode exhibited binding affinity comparable to the small molecule T6Q in the crystal structure (PDB ID: 4BCF), highlighting the essential role of molecular dynamics simulation in capturing a plausible binding pose bridging docking and absolute binding free energy calculations. Finally, structural modifications based on these findings further enhanced the binding affinity with CDK9. The results revealed that enhancing the molecule's rigidity through ring formation, while maintaining the major interactions, reduced the entropy loss during the binding process and, thus, enhanced binding affinities.

A density functional theory study on the mechanism of toluene from dimethylcyclopentane catalyzed by the [GaH]2+ active site of Ga-ZSM-5.

The ONIOM (ωb97xd/6-31G(d,p):pm6) method was used to study the reaction mechanism of dimethylcyclopentane to toluene by the [GaH]2+ active site of Ga-ZSM-5. The results showed that the rate-determining step in the dimethylcyclopentane aromatization process is the ring expansion process. Compared to those of methylcyclopentane to benzene (D. D. Zhang, H. Y. Liu, L. X. Ling, H. R. Zhang, R. G. Zhang, P. Liu and B. J. Wang, Phys. Chem. Chem. Phys., 2021, 23, 10988-11003.), the free energy barriers of dimethylcyclopentane to toluene are significantly decreased, indicating that toluene is easier to produce than benzene, which confirmed the experimental results that a higher proportion of toluene than benzene is produced in the MTA process.

Application and effect of tension-reducing suture in surgical treatment of hypertrophic scar.

PURPOSE: To investigate the application and effectiveness of tension-reducing suture in the repair of hypertrophic scars. METHODS: A retrospective analysis of clinical data was conducted on 82 patients with hypertrophic scars treated at the Department of Burns and Plastic Surgery of Nanjing Drum Tower Hospital from September 2021 to December 2022. Patients were operated with combination of heart-shaped tension-reducing suturing technique and looped, broad, and deep buried (LBD) suturing technique or conventional suture method. Outcomes of surgical treatment were assessed before and 6 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). RESULTS: Improvements were achieved on scar quality compared to that preoperatively, with a reduction in scar width (1.7 ± 0.6 cm vs. 0.7 ± 0.2 cm, P < 0.001). Assessment using the POSAS and VSS scales showed significant improvements in each single parameter and total score compared to preoperative values (P < 0.05). The Combination method group achieved better score in total score of VSS scale, in color, stiffness, thickness and overall opinion of PSAS scale, and in vascularity, thickness, pliability and overall opinion of OSAS scale. CONCLUSION: The amalgamation of the heart-shaped tension-reducing suturing technique and the LBD suturing technique has shown promising outcomes, garnering notably high levels of patient satisfaction in the context of hypertrophic scar repair. Patients have exhibited favorable postoperative recoveries, underscoring the clinical merit and the prospective broader applicability of this approach in the realm of hypertrophic scar management.

CXC chemokine ligand-10 promotes the accumulation of monocyte-like myeloid-derived suppressor cells by activating p38 MAPK signaling under tumor conditions.

CXC chemokine ligand-10 (CXCL10) is a small (10 kDa) secretory protein in the CXC subfamily of cytokines. CXCL10 has been reported to play an important role in antitumor immunity as a chemotactic factor. Tumor development is always accompanied by the formation of an immunosuppressive tumor microenvironment, and the role of CXCL10 in tumor immunosuppression remains unclear. Here, we reported that CXCL10 expression was significantly upregulated in mice with melanoma, and tumor cells secreted large amounts of CXCL10. Myeloid-derived suppressor cells (MDSCs) are an important part of the immunosuppressive tumor microenvironment. Our results showed that CXCL10 promoted the proliferation of monocyte-like (mo)-MDSCs by activating the p38 MAPK signaling pathway through CXCR3, which led to the abnormal accumulation of mo-MDSCs under tumor conditions. This finding provides a new understanding of the mechanism by which a tumor-induced immunosuppressive microenvironment forms and suggests that CXCL10 could be a potential intervention target for slowing tumor progression.

Cytokines as drivers: Unraveling the mechanisms of epithelial-mesenchymal transition in COVID-19 lung fibrosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like other viruses, can induce proliferation of myofibroblasts and even lead to fibrosis in the lung. Epithelial-mesenchymal transition (EMT) is thought to play an essential role in the pathogenesis of Coronavirus disease 19 (COVID-19). EMT is originally a critical process that regulates the development of different tissues in the embryo, but in inflammatory situations, EMT tries to be activated again to control inflammation or even heal inflammatory damage. However, in pathological situations, such as chronic viral infections (e.g., COVID-19) or pulmonary fibrosis initiation, this benign healing transforms into sinister nature, pushing the lung into the fibrotic process. Notably, the cytokines released by inflammatory cells and the chronic inflammatory microenvironment shared by fibrotic cells promote each other as critical factors in the induction of pathological EMT. In the induction of SARS-CoV-2 virus, cytokines are an essential mediator of EMT transformation, and a summary of whether COVID-19 patients, during the infection phase, have many persistent inflammatory mediators (cytokines) that are a causative factor of EMT has not yet appeared. The following common signaling drivers, including Transforming growth factor beta (TGF-ß), cytokines, Notch signaling pathway, Wnt and hypoxia signaling pathways, drive the regulation of EMT. In this review, we will focus on 3 key EMT signaling pathways: TGF-ß, Leucine zipper transcription factor like 1 (LZTFL1) and the common interleukin family expressed in the lung. TGF-ß-induced SNAIL and LZTFL1 were identified as regulatory EMT in COVID-19. For cytokines, the interleukin family is a common inducer of EMT and plays an essential role in the formation of the microenvironment of fibrosis. We sought to demonstrate that cytokines act as "communicators" and build the "microenvironment" of fibrosis together with EMT as a "bridge" to induce EMT in fibrosis. The mechanisms utilized by these two pathways could serve as templates for other mesenchymal transformations and provide new potential therapeutic targets.

Boosting Electrochemical Catalysis and Nonenzymatic Sensing Toward Glucose by Single-Atom Pt Supported on Cu@CuO Core-Shell Nanowires.

It is critical to develop high-performance electrocatalyst for electrochemical nonenzymatic glucose sensing. In this work, a single-atom Pt supported on Cu@CuO core-shell nanowires (Pt1 /Cu@CuO NWs) for electrochemical nonenzymatic glucose sensor is designed. Pt1 /Cu@CuO NWs exhibit excellent electrocatalytic oxidation toward glucose with 70 mV lower onset potential (0.131 V) and 2.4 times higher response current than Cu NWs. Sensors fabricated using Pt1 /Cu@CuO NWs also show high sensitivity (852.163 µA mM-1 cm-2 ), low detection limit (3.6 µM), wide linear range (0.01-5.18 µM), excellent selectivity, and great long-term stability. The outstanding sensing performance of Pt1 /Cu@CuO NWs, investigated by experiments and density functional theory (DFT) calculations, is attributed to the synergistic effect between Pt single atoms and Cu@CuO core-shell nanowires that generates strong binding energy of glucose on the nanowires. The work provides a new pathway for exploring highly active SACs for electrochemical nonenzymatic glucose sensor.

Biochemical propensity mapping for structural and functional anatomy of importin α IBB domain.

Importin α has been described as a nuclear protein transport receptor that enables proteins synthesized in the cytoplasm to translocate into the nucleus. Besides its function in nuclear transport, an increasing number of studies have examined its non-nuclear transport functions. In both nuclear transport and non-nuclear transport, a functional domain called the IBB domain (importin ß binding domain) plays a key role in regulating importin α behavior, and is a common interacting domain for multiple binding partners. However, it is not yet fully understood how the IBB domain interacts with multiple binding partners, which leads to the switching of importin α function. In this study, we have distinguished the location and propensities of amino acids important for each function of the importin α IBB domain by mapping the biochemical/physicochemical propensities of evolutionarily conserved amino acids of the IBB domain onto the structure associated with each function. We found important residues that are universally conserved for IBB functions across species and family members, in addition to those previously known, as well as residues that are presumed to be responsible for the differences in complex-forming ability among family members and for functional switching.

Automated design of freeform imaging systems for automotive heads-up display applications.

The freeform imaging system is playing a significant role in developing an optical system for the automotive heads-up display (HUD), which is a typical application of augmented reality (AR) technology. There exists a strong necessity to develop automated design algorithms for automotive HUDs due to its high complexity of multi-configuration caused by movable eyeballs as well as various drivers' heights, correcting additional aberrations introduced by the windshield, variable structure constraints originated from automobile types, which, however, is lacking in current research community. In this paper, we propose an automated design method for the automotive AR-HUD optical systems with two freeform surfaces as well as an arbitrary type of windshield. With optical specifications of sagittal and tangential focal lengths, and required structure constraints, our given design method can generate initial structures with different optical structures with high image quality automatically for adjusting the mechanical constructions of different types of cars. And then the final system can be realized by our proposed iterative optimization algorithms with superior performances due to the extraordinary starting point. We first present the design of a common two-mirror HUD system with longitudinal and lateral structures with high optical performances. Moreover, several typical double mirror off-axis layouts for HUDs were analyzed from the aspects of imaging performances and volumes. The most suitable layout scheme for a future two-mirror HUD is selected. The optical performance of all the proposed AR-HUD designs for an eye-box of 130 mm × 50 mm and a field of view of 13° × 5° is superior, demonstrating the feasibility and superiority of the proposed design framework. The flexibility of the proposed work for generating different optical configurations can largely reduce the efforts for the HUD design of different automotive types.

Inhibition of ERK downregulates autophagy via mitigating mitochondrial fragmentation to protect SH-SY5Y cells from OGD/R injury.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is the main cause leading to high mortality and neurological disability in patients with cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Our previous study found that extracellular signal-regulated kinase (ERK) activation, dynamin-related protein1 (Drp1)/Mitofusin2 (Mfn2)-dependent mitochondrial dynamics imbalance, and excessive autophagy were involved in the mechanism of nerve injury after CA/CPR. However, the specific pathological signaling pathway is still unknown. This study aimed to explore the molecular function changes of ERK-Drp1/Mfn2-autophagy signaling pathway in SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, to further clarify the pathophysiological mechanism of CIRI, and to provide a new strategy for cerebral protection after CIRI. METHODS: SH-SY5Y cells were pretreated with drugs 24 h before OGD/R. The Drp1 and Mfn2 knockdown were adopted small interfering RNAs. The overexpression of p-Drp1S616 and Mfn2 were used recombinant plasmids. The expression levels of mitochondrial dynamics proteins (p-Drp1, Drp1, Mfn2, Mfn1 and Opa1) and autophagy markers (LC3, Beclin1 and p62) were measured with the Western blotting. The mRNA levels after transfection were determined by PCR. Cell injury and viability were evaluated with released LDH activity and CCK8 assay kits. Mitochondria morphology and autophagosome were observed under transmission electron microscopy. Mitochondrial function was detected by the mitochondrial permeability transition pore assay kit. The co-expression of p-ERK, p-Drp1 and LC3 was assessed with multiple immunofluorescences. One-way analysis of variance followed by least significance difference post hoc analysis (for equal homogeneity) or Dunnett's T3 test (for unequal homogeneity) were used for statistical tests. RESULTS: ERK inhibitor-PD98059 (PD) protects SH-SY5Y cells from OGD/R-induced injury; while ERK activator-TPA had the opposite effect. Similar to autophagy inhibitor 3-MA, PD downregulated autophagy to improve cell viability; while autophagy activator-rapamycin further aggravated cell death. PD and Drp1-knockdown synergistically attenuated OGD/R-induced Drp1 activation, mPTP opening and cell injury; overexpression of Drp1S616E or ablating Mfn2 partly abolished the protective effects of PD. Multiple immunofluorescences showed that p-ERK, p-Drp1 and LC3 were co-expressed. CONCLUSION: Inhibition of ERK downregulates autophagy via reducing Drp1/Mfn2-dependent mitochondrial fragmentation to antagonize mitochondrial dysfunction and promotes cell survival in the SH-SY5Y cells OGD/R model. Video Abstract.

Radiosensitization of Nasopharyngeal Carcinoma by Graphene Oxide Nanosheets to Reduce Bcl-2 Level.

There are many treatments for nasopharyngeal carcinoma (NPC), but none of them are very effective. Radiotherapy is used extensively in NPC treatment, but radioresistance is a major problem. Graphene oxide (GO) has been previously studied in cancer treatment, and this study is aimed to explore its role in radiosensitization of NPC. Therefore, graphene oxide nanosheets were prepared, and the relationship between GO and radioresistance was explored. The GO nanosheets were synthesized by a modified Hummers' method. The morphologies of the GO nanosheets were characterized by field-emission environmental scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The morphological changes and radiosensitivity of C666-1 and HK-1 cells with or without the GO nanosheets were observed by an inverted fluorescence microscopy and laser scanning confocal microscopy (LSCM). Colony formation assay and Western Blot were applied for analysis of NPC radiosensitivity. The as-synthesized GO nanosheets have lateral dimensions (sizes ∼1 µm) and exhibit a thin wrinkled two-dimensional lamellar structure with slight folds and crimped edges (thickness values ∼1 nm). C666-1 cells with the GO was significantly changed the morphology of cells postirradiation. The full field of view visualized by a microscope showed the shadow of dead cells or cell debris. The synthesized graphene oxide nanosheets inhibited cell proliferation, promoted cell apoptosis, and inhibited the expression of Bcl-2 in C666-1 and HK-1 cells but increased the level of Bax. The GO nanosheets could affect the cell apoptosis and reduce the pro-survival protein Bcl-2 related to the intrinsic mitochondrial pathway. The GO nanosheets could enhance radiosensitivity, which might be a radioactive material in NPC cells.

Impacts of the COVID-19 pandemic on life expectancy at birth in Asia.

OBJECTIVE: To investigate the impact of the COVID-19 pandemic on life expectancy at birth (e0) for 51 Asian countries and territories from January 1, 2020 to December 31, 2021. METHOD: Based on age-sex-specific mortality used for estimating the changes in e0 for years 2019, 2020, and 2021 from the 2022 revision of the World Population Prospects, we employed Arriaga's discrete method to decompose changes in e0 into both absolute and relative contributions of changes in age-specific death rate, and further obtained the age-sex-specific contribution to changes in e0 by country/territory and period (i.e., 2019-2020 and 2020-2021) for Asia. FINDINGS: The COVID-19 pandemic reduced 1.66 years in e0 of the Asian population from 2019 to 2021, slightly lower than the world average of 1.74 years. South Asia had a high loss of 3.01 years, whereas Eastern Asia had almost no changes. Oman, Lebanon, India, Armenia, Azerbaijan, Indonesia, and the Philippines experienced a high loss of above 2.5 years in e0. Despite significant national and territorial variations, the decline of e0 in Asia was mostly from the age group of 60-79 years, followed by age groups of 80 + and 45-59 years; and age groups of children contributed little (i.e., 0-4 and 5-14 years old). Males suffered more losses than females in this pandemic. Asian nations saw less loss in e0 in the second year of the pandemic, i.e., 2020-2021, than in the first year, i.e., 2019-2020, but this recovery trend was not observed in Southern Asia and South-Eastern Asia. Countries from Central Asia and Western Asia, such as Kazakhstan, Armenia, Azerbaijan, Lebanon, and Oman, had extraordinarily more losses in e0 in the first year at ages around 70. CONCLUSION: The COVID-19 pandemic had significantly affected e0 of Asian populations, and most contribution to the reduction of e0 came from the three older age groups, 60-79 years, 80 + years, and 45-59 years, with great variations across countries/territories. Our findings could have important implications for development of more resilient public health systems in Asian societies with better policy interventions for vulnerable demographic groups.

Drinking water disinfection byproduct iodoacetic acid affects thyroid hormone synthesis in Nthy-ori 3-1 cells.

Iodoacetic acid (IAA) is an emerging and the most genotoxic iodinated disinfection byproduct to date. IAA can disrupt the thyroid endocrine function in vivo and in vitro, but the underlying mechanisms remain unclear. In this work, transcriptome sequencing was used to investigate the effect of IAA on the cellular pathways of human thyroid follicular epithelial cell line Nthy-ori 3-1 and determine the mechanism of IAA on the synthesis and secretion of thyroid hormone (TH) in Nthy-ori 3-1 cells. Results of transcriptome sequencing indicated that IAA affected the TH synthesis pathway in Nthy-ori 3-1 cells. IAA reduced the mRNA expression of thyroid stimulating hormone receptor, sodium iodide symporter, thyroid peroxidase, thyroglobulin, paired box 8 and thyroid transcription factor-2, inhibited the cAMP/PKA pathway and Na+-K+-ATPase, and decreased the iodine intake. The results were confirmed by our previous findings in vivo. Additionally, IAA downregulated glutathione and the mRNA expression of glutathione peroxidase 1, leading to increased reactive oxygen species production. This study is the first to elucidate the mechanisms of IAA on TH synthesis in vitro. The mechanisms are associated with down-regulating the expression of genes related to TH synthesis, inhibiting iodine uptake, and inducing oxidative stress. These findings may improve future health risk assessment of IAA on thyroid in human.

[Alterations in the intestinal microbiota of preterm infants with neurodevelopmental impairments: a prospective cohort study]. / ç¥žç»å‘è‚²æŸå®³æ—©äº§å„¿è‚ é“èŒç¾¤å˜åŒ–çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI. METHODS: In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups. RESULTS: Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05). CONCLUSIONS: There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.

Single-Atom Pt Boosting Electrochemical Nonenzymatic Glucose Sensing on Ni(OH)2/N-Doped Graphene.

Conventional nanomaterials in electrochemical nonenzymatic sensing face huge challenge due to their complex size-, surface-, and composition-dependent catalytic properties and low active site density. In this work, we designed a single-atom Pt supported on Ni(OH)2 nanoplates/nitrogen-doped graphene (Pt1/Ni(OH)2/NG) as the first example for constructing a single-atom catalyst based electrochemical nonenzymatic glucose sensor. The resulting Pt1/Ni(OH)2/NG exhibited a low anode peak potential of 0.48 V and high sensitivity of 220.75 µA mM-1 cm-2 toward glucose, which are 45 mV lower and 12 times higher than those of Ni(OH)2, respectively. The catalyst also showed excellent selectivity for several important interferences, short response time of 4.6 s, and high stability over 4 weeks. Experimental and density functional theory (DFT) calculated results reveal that the improved performance of Pt1/Ni(OH)2/NG could be attributed to stronger binding strength of glucose on single-atom Pt active centers and their surrounding Ni atoms, combined with fast electron transfer ability by the adding of the highly conductive NG. This research sheds light on the applications of SACs in the field of electrochemical nonenzymatic sensing.

Automatic design of an extreme ultraviolet lithography objective system based on the Seidel aberration theory.

In this paper, a method is proposed to solve the initial optical structure of an off-axis multimirror system for an extreme ultraviolet lithography (EUVL) application. By tracing the characteristic rays, the primary aberration can be expressed as a function of the distance and curvature based on the Seidel aberration theory. The initial structure with a favorable aberration performance is calculated when the function value is 0. We solve two different initial structures with an off-axis, six-mirror configuration with different optical powers. The NA of the finally optimized optical system is 0.25, the wavefront aberration rms value is less than 0.04λ, and the absolute distortion is below 1.2 nm.

Pak2 kinase promotes cellular senescence and organismal aging.

Cellular senescence defines an irreversible cell growth arrest state linked to loss of tissue function and aging in mammals. This transition from proliferation to senescence is typically characterized by increased expression of the cell-cycle inhibitor p16INK4a and formation of senescence-associated heterochromatin foci (SAHF). SAHF formation depends on HIRA-mediated nucleosome assembly of histone H3.3, which is regulated by the serine/threonine protein kinase Pak2. However, it is unknown if Pak2 contributes to cellular senescence. Here, we show that depletion of Pak2 delayed oncogene-induced senescence in IMR90 human fibroblasts and oxidative stress-induced senescence of mouse embryonic fibroblasts (MEFs), whereas overexpression of Pak2 accelerated senescence of IMR90 cells. Importantly, depletion of Pak2 in BubR1 progeroid mice attenuated the onset of aging-associated phenotypes and extended life span. Pak2 is required for expression of genes involved in cellular senescence and regulated the deposition of newly synthesized H3.3 onto chromatin in senescent cells. Together, our results demonstrate that Pak2 is an important regulator of cellular senescence and organismal aging, in part through the regulation of gene expression and H3.3 nucleosome assembly.

Machine Learning Based Non-Enhanced CT Radiomics for the Identification of Orbital Cavernous Venous Malformations: An Innovative Tool.

PURPOSE: To evaluate the capability of non-enhanced computed tomography (CT) images for distinguishing between orbital cavernous venous malformations (OCVM) and non-OCVM, and to identify the optimal model from radiomics-based machine learning (ML) algorithms. METHODS: A total of 215 cases of OCVM and 120 cases of non- OCVM were retrospectively analyzed in this study. A stratified random sample of 268 patients (80%) was used as the training set (172 OCVM and 96 non-OCVM); the remaining data were used as the testing set. Six feature selection techniques and thirteen ML models were evaluated to construct an optimal classification model. RESULTS: There were statistically significant differences between the OCVM and non-OCVM groups in the density and tumor location (P  < 0.05), whereas other indicators were comparable (age, gender, sharp, P > 0.05). Linear regression (area under the curve [AUC] = 0.9351; accuracy = 0.8657) and Stochastic Gradient Descent (AUC = 0.9448; accuracy = 0.8806) classifiers, both of which coupled with the f test and L1-based feature selection method, achieved optimal performance. The support vector machine (AUC = 0.9186; accuracy = 0.8806), Random Forest (AUC = 0.9288; accuracy = 0.8507) and eXtreme Gradient Boosting (AUC = 0.9147; accuracy = 0.8507) classifier combined with f test method showed excellent average performance among our study, respectively. CONCLUSIONS: The effect of non-enhanced CT images in OCVM not only can help ophthalmologist to find and locate lesion, but also bring great help for the qualitative diagnosis value using radiomic- based ML algorithms.

Multi-Scale Superpixel-Guided Structural Profiles for Hyperspectral Image Classification.

Hyperspectral image classification has received a lot of attention in the remote sensing field. However, most classification methods require a large number of training samples to obtain satisfactory performance. In real applications, it is difficult for users to label sufficient samples. To overcome this problem, in this work, a novel multi-scale superpixel-guided structural profile method is proposed for the classification of hyperspectral images. First, the spectral number (of the original image) is reduced with an averaging fusion method. Then, multi-scale structural profiles are extracted with the help of the superpixel segmentation method. Finally, the extracted multi-scale structural profiles are fused with an unsupervised feature selection method followed by a spectral classifier to obtain classification results. Experiments on several hyperspectral datasets verify that the proposed method can produce outstanding classification effects in the case of limited samples compared to other advanced classification methods. The classification accuracies obtained by the proposed method on the Salinas dataset are increased by 43.25%, 31.34%, and 46.82% in terms of overall accuracy (OA), average accuracy (AA), and Kappa coefficient compared to recently proposed deep learning methods.