Unique Morphological Changes Research Articles

CK-666 protects against ferroptosis and renal ischemia-reperfusion injury through a microfilament-independent mechanism

Ferroptosis is a type of regulated cell death driven by iron-dependent accumulation of lipid peroxidation, exhibiting unique morphological changes. While actin microfilaments are crucial for various cellular processes, including morphogenesis, motility, endocytosis, and cell death, their role in ferroptosis remains unclear. Here, our study reveals that actin microfilaments undergo remodeling and disassembly during ferroptosis. Interestingly, inhibitors that target actin microfilament remodeling do not affect cell sensitivity to ferroptosis, with the exception of CK-666 and its structural analogue CK-636. Mechanistically, CK-666 attenuates ferroptosis independently of its canonical function in inhibiting the Arp2/3 complex. Further investigation revealed that CK-666 modulates the ferroptotic transcriptome, prevents lipid degradation, and diminishes lipid peroxidation. In addition, CK-666 does not impact the labile iron pool within cells, nor does the inhibition of FSP1 impact its anti-ferroptosis activity. Notably, the results of DPPH assay and liposome leakage assay suggest that CK-666 mitigates ferroptosis by directly eliminating lipid peroxidation. Importantly, CK-666 significantly ameliorated renal ischemia-reperfusion injury and ferroptosis in renal tissue, underscoring its potential therapeutic impact.

Comparative morphology in the context of facial reduction: Modularity in primate, dog, and bat crania.

Biological variation in the mammalian skull is the product of a series of factors including changes in gene expression, developmental timing, and environmental pressures. When considering the diversity of extant mammalian crania, it is important to understand these mechanisms that contribute to cranial growth and in turn, how differences in cranial morphology have been attained. Various researchers, including Dr. Sue Herring, have proposed a variety of mechanisms to explain the process of cranial growth. This work has set the foundation on which modern analysis of craniofacial morphology happens today. This study focused on the analysis of modularity in three mammalian taxa, all of which exhibit facial reduction. Specifically, we examined facial reduction as a morphological phenomenon through the use of two-module and six-module modularity hypotheses. We recorded three-dimensional coordinate data for 55 cranial landmarks that allowed us to analyze differences in cranial shape in these three taxa (primates n = 88, bats n = 64, dogs n = 81). When assessing modularity within the two-module modularity hypothesis specifically, dogs exhibited the lowest levels of modularity, while bats and primates both showed a slightly more modular covariance structure. We further assessed modularity in the same sample using the Goswami six-module model, where again dogs exhibited a low degree of modularity, with bats and primates being more moderate. We then broke the sample into subsets by analyzing each morphotype separately. We hypothesized that the modularity would be more pronounced in the brachycephalic morphotype. Surprisingly, we found that in brachycephalic dogs, normocephalic dogs, brachycephalic primates, and normocephalic primates, there was a moderate degree of modularity. Brachycephalic bats had a low degree of modularity, while normocephalic bats were the most modular group observed in this study. Based on these results, it is evident that facial reduction is a complex and multifaceted phenomenon with unique morphological changes observed in each of the three taxa studied.

Morphology Control of Au-Ni Hybrid Nanoparticles: Exploring Heterostructures and Optical Tuning.

Hybrid nanoparticles (NPs) have attracted considerable attention because of their ability to provide diverse properties by integrating the inherent properties of multiple components; however, synthetic strategies to control their morphology remain unexplored. In this study, a new method was used to control the morphology and optical properties of Au-Ni heterostructure (ANH) NPs. Unique morphological changes were observed by varying the Au/Ni precursor ratio from 2:1 to 1:4, exhibiting a shape transformation from dumbbell-like to quasi-spherical owing to the Ni NP size expansion, whereas the Au NP maintained their size. Moreover, increasing the Ni ratio induced plasmonic band broadening and wavelength redshift, resulting in color changes from red to navy and black. In terms of the structure, the atomic orientation of the crystallite showed that even a large lattice mismatch can result in heterojunctions at the NPs. In addition, the reaction aliquots uncovered heterogeneous nucleation and growth of ANH NPs in the colloidal system, demonstrating Ni reduction on the preformed Au NP owing to the reduction in potential gap. This study provides new insights into controlling the morphology of hybrid NPs using colloidal synthesis and the design of optimized materials for various applications.

Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases.

Cerebrovascular diseases and their sequalae, such as ischemic stroke, chronic cerebral hypoperfusion, and vascular dementia are significant contributors to adult disability and cognitive impairment in the modern world. Astrocytes are an integral part of the neurovascular unit in the CNS and play a pivotal role in CNS homeostasis, including ionic and pH balance, neurotransmission, cerebral blood flow, and metabolism. Astrocytes respond to cerebral insults, inflammation, and diseases through unique molecular, morphological, and functional changes, collectively known as reactive astrogliosis. The function of reactive astrocytes has been a subject of debate. Initially, astrocytes were thought to primarily play a supportive role in maintaining the structure and function of the nervous system. However, recent studies suggest that reactive astrocytes may have both beneficial and detrimental effects. For example, in chronic cerebral hypoperfusion, reactive astrocytes can cause oligodendrocyte death and demyelination. In this review, we will summarize the (1) roles of ion transporter cascade in reactive astrogliosis, (2) role of reactive astrocytes in vascular dementia and related dementias, and (3) potential therapeutic approaches for dementing disorders targeting reactive astrocytes. Understanding the relationship between ion transporter cascade, reactive astrogliosis, and cerebrovascular diseases may reveal mechanisms and targets for the development of therapies for brain diseases associated with reactive astrogliosis.

Subphase Exchange Cell for Studying Fluid-Fluid Interfaces with Optical Microscopy.

A subphase exchange cell was designed to observe fluid-fluid interfaces with a conventional optical microscope while simultaneously changing the subphase chemistry. Materials including phospholipids, asphaltenes, and nanoparticles at fluid-fluid interfaces exhibit unique morphological changes as a function of the bulk-phase chemistry. These changes can affect their interfacial material properties and, ultimately, the emergent bulk material properties of the films, foams, and emulsions produced from such interfacial systems. In this work, we combine experiments, computational fluid dynamics simulations, and modeling to establish the operating parameters for a subphase exchange cell of this type to reach a desired concentration. We used the experimental setup to investigate changes to a graphene film during a common wet-etching transfer process. Observations reveal that capillary interactions can induce defects and deformations in the graphene film during the wet-etching process, an important finding that must be considered for any wet-etching transfer technique for 2D materials. More generally, conventional optical microscopy was shown to be able to image the dynamics of interfacial systems during a bulk-phase chemistry change. Potential applications for this equipment and technique include observing morphological dynamics of phospholipid film structure with subphase salinity, asphaltene film structure with subphase pH, and particle film synthesis with subphase chemistry.

Abstract 14454: Catheter Ablation of Atrial Fibrillation Reverses Morphological Changes of the Mitral Valve and Ameliorates Atrial Functional Mitral Regurgitation

Background: We previously reported that atrial functional mitral regurgitation (A-FMR) occurs with morphological changes of the mitral valve and can be improved by catheter ablation (CA) of atrial fibrillation (AF). However, it is unclear whether the unique morphological changes in the time-course of AF persistence are reversible with sinus rhythm restoration with CA. Aims: The aims of this study were 1) to compare morphological differences among paroxysmal AF (PAF) w/o MR, non-paroxysmal AF (NPAF) w/o MR, and A-FMR, and 2) to examine changes in degree of MR and morphology of the mitral valve after CA in patients with A-FMR. Methods: This is a multicenter (4 hospitals in Fukuoka) retrospective observational study. Protocol 1 : Eighty-four patients undergoing initial CA for AF (from 2010.January to 2021.May) were selected and divided into 3 groups after matching on age (68±8 y.o), sex (19 males), and body surface area (1.7±0,2 m 2 ); PAF w/o MR, NPAF w/o MR, and A-FMR (n=28 in each group). A-FMR was defined as at least mild MR accompanying with NPAF, preserved LVEF (≧ 50%), and no evidence of valve degeneration and other structurally heart diseases. Protocol 2 : Fifty-five patients with A-FMR (19 males, 71±9 y.o.) undergoing initial CA were enrolled. Clinical variables and echocardiographic parameters were analyzed. Results: In protocol 1, tethering angles of anterior and posterior mitral leaflet (AML and PML) were smaller in patients with A-FMR compared with PAF w/o MR (Table1). PML length was shorter in A-FMR than other groups (Table1). In protocol 2, the degree of MR was significantly reduced (Figure, p=0.0013) associated with reduction in MR vena contracta width and MR area (p<0.001) at 11±7 months after CA. Tethering angles of AML and PML were increased after CA (Table2). Conclusion: A-FMR occurs via unique morphological changes of the mitral apparatus along with AF persistence and can be improved by CA of AF with significant reversals of the morphological changes.

Morphological Changes on Neuromuscular Ultrasound in Nerves Distal to Gunshot Injuries (P14-8.003)

<h3>Objective:</h3> The aim of this study was to describe unique morphological changes on neuromuscular ultrasound in nerves distal to gunshot injuries and to identify the frequency with which these changes occur. <h3>Background:</h3> A spectrum of peripheral nerve injuries is seen secondary to gunshot wounds. The assessment of these injuries has traditionally been limited to clinical evaluation and supplemented by electrodiagnostic testing. Neuromuscular ultrasound is a versatile imaging technique that has been used to assess peripheral nerve structural integrity, neuroma formation or other structural abnormalities following trauma. The extent of sonographic changes at nerve segments distal to gunshot injuries has not been well described. <h3>Design/Methods:</h3> A retrospective chart review was performed on all patients referred to the electromyography laboratory with peripheral nerve injuries from gunshot wounds who also had neuromuscular ultrasound performed as part of their evaluation. <h3>Results:</h3> 17 patients were evaluated. All had either a nerve transection or neuroma in continuity of a major upper or lower extremity nerve at the site of the gunshot wound. 13 (76%), however, also had significant morphological changes in distal segments of the injured nerve and 12 (71%) had changes in other nearby distal nerves. Common findings included enlarged nerve cross sectional area, enlarged fascicles and hypoechogenicity. One patient had a repeat study nine months following the initial study which demonstrated improvement in sciatic nerve cross sectional area, decreasing from 130 mm² to 79 mm². <h3>Conclusions:</h3> Following gunshot injuries, major morphological changes commonly occur in nerve segments distal to the injury; both in the injured nerve and nearby nerves. Marked enlargement of hypoechoic fascicles is seen along with enlarged cross-sectional area of nerve. We hypothesize that ballistic trauma, such as gunshot injuries, can lead to concussive damage that disrupts the normal architecture of distal nerves. Follow up ultrasound studies suggest that these changes may be partially reversible. <b>Disclosure:</b> Dr. Fagan has nothing to disclose. Dr. Geiger has nothing to disclose. Dr. Preston has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for FBI, US Attorney, Insurance Fraud Investigative Units. Dr. Preston has received publishing royalties from a publication relating to health care.

Morphological guided sphere to dendrite BiVO4 for highly efficient organic pollutant removal and photoelectrochemical performance under solar light

Monoclinic BiVO4 (m-BiVO4) has been reported as promising phase for solar light driven photocatalysis. However, in the case of morphology guided BiVO4 with different synthetic conditions maintaining the m-BiVO4 phase remains a substantial challenge for achieving an efficient photocatalyst driven by solar light. Herein, a simple hydrothermal approach was used to produce well-defined template free m-BiVO4 dendrites with distinct branches for photo catalytically removal of organic pollutant and photocurrent generation. The development of monoclinic dendrite BiVO4 was confirmed after comprehensive structural, morphological, and optical examinations. FE-SEM images of m-BiVO4 revealed transformation of spherical to dendritic morphology with distinct branches by simply changing the HNO3 to NaOH ratios from 2:1 to 2:2, which are named as BVO 2-1 and BVO 2-2, respectively. The BVO 2-2 dendrites exhibited improved activity of 98% towards methylene blue (MB) photodegradation upon simulated solar light irradiation. The BVO 2-2 dendrites photoelectrode showed an outstanding photocurrent density of 1.4245 mAcm−2 than that of the BVO 2-1 spherical photoelectrode (0.7367 mAcm−2). Enhanced photocatalytic and photoelectrochemical action, could be ascribed to the unique morphological changes provides photoactive sites, harvest more light utilization together with higher separation of e−/h+ pairs. Furthermore, photocatalytic mechanism is investigated based on scavenger trapping agent, valence band XPS, UV Visible DRS and PL study. Our findings could pave the way for the development of dendritic nanostructure photocatalysts with improved photocatalytic activity.

Assessment of Anatomical Changes in Advanced Chronic Venous Insufficiency Using Artificial Intelligence ) and Machine Learning Techniques

Advanced chronic venous insufficiency (CVI) is characterized by significant and unique morphological changes in the legs such as swelling, discoloration, loss of subcutaneous and muscle tissue in the lower part of the leg (inverted Champaign bottle appearance) and ulceration. These changes are not uniform and do not progress linearly with time. Widely used reporting tools like CEAP classification are descriptive. Currently, there are no reliable and objective methods to assess and monitor these soft tissue changes with time and after therapy.

Combining Spectral and Texture Features of UAV Images for the Remote Estimation of Rice LAI throughout the Entire Growing Season

Leaf area index (LAI) estimation is very important, and not only for canopy structure analysis and yield prediction. The unmanned aerial vehicle (UAV) serves as a promising solution for LAI estimation due to its great applicability and flexibility. At present, vegetation index (VI) is still the most widely used method in LAI estimation because of its fast speed and simple calculation. However, VI only reflects the spectral information and ignores the texture information of images, so it is difficult to adapt to the unique and complex morphological changes of rice in different growth stages. In this study we put forward a novel method by combining the texture information derived from the local binary pattern and variance features (LBP and VAR) with the spectral information based on VI to improve the estimation accuracy of rice LAI throughout the entire growing season. The multitemporal images of two study areas located in Hainan and Hubei were acquired by a 12-band camera, and the main typical bands for constituting VIs such as green, red, red edge, and near-infrared were selected to analyze their changes in spectrum and texture during the entire growing season. After the mathematical combination of plot-level spectrum and texture values, new indices were constructed to estimate rice LAI. Comparing the corresponding VI, the new indices were all less sensitive to the appearance of panicles and slightly weakened the saturation issue. The coefficient of determination (R2) can be improved for all tested VIs throughout the entire growing season. The results showed that the combination of spectral and texture features exhibited a better predictive ability than VI for estimating rice LAI. This method only utilized the texture and spectral information of the UAV image itself, which is fast, easy to operate, does not need manual intervention, and can be a low-cost method for monitoring crop growth.

TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis

How amphipathic phospholipids are shuttled between the membrane bilayer remains an essential but elusive process, particularly at the endoplasmic reticulum (ER). One prominent phospholipid shuttling process concerns the biogenesis of APOB-containing lipoproteins within the ER lumen, which may require bulk trans-bilayer movement of phospholipids from the cytoplasmic leaflet of the ER bilayer. Here, we show that TMEM41B, present in the lipoprotein export machinery, encodes a previously conceptualized ER lipid scramblase mediating trans-bilayer shuttling of bulk phospholipids. Loss of hepatic TMEM41B eliminates plasma lipids, due to complete absence of mature lipoproteins within the ER, but paradoxically also activates lipid production. Mechanistically, scramblase deficiency triggers unique ER morphological changes and unsuppressed activation of SREBPs, which potently promotes lipid synthesis despite stalled secretion. Together, this response induces full-blown nonalcoholic hepatosteatosis in the TMEM41B-deficient mice within weeks. Collectively, our data uncovered a fundamental mechanism safe-guarding ER function and integrity, dysfunction of which disrupts lipid homeostasis.

N-doped MWCNTs from catalyst-free, direct pyrolysis of commercial glue

We report a unique, catalyst-free, direct pyrolysis process to obtain nitrogen-doped multiwall carbon nanotubes (N-MWCNTs). The process includes the polymerization of ethyl cyanoacrylate (ECA) based commercial super glue with aqueous NaCl solution. The resultant poly-ethyl cyanoacrylate (PECA)-NaCl composite was washed to remove NaCl and subsequently calcined at 1000 °C in an inert atmosphere to obtain carbon nanotubes. The field emission scanning electron microscopy and high-resolution transmission electron microscopy studies confirm that these are nitrogen-doped multiwall carbon nanotubes (N-MWCNTs) with diameters in the range of 80–110 nm. Compared to conventional MWCNTs, these nanotubes exhibit distinct multilayer stacking of carbon with short-range ordering with interlayer spacing slightly larger than graphitic carbon. XPS studies reveal the presence of doped nitrogen substituting for carbon atoms, whereas Raman spectroscopy data shows that these nitrogen-doped nanotubes exhibit nanocrystalline, graphitic carbon. Washing of PECA-NaCl composite results in the removal of NaCl leading to the unique porous PECA intermediate structure. These unique morphological changes and structural transformations of PECA in DI water along with the peculiar degradation behavior of PECA during the heat treatment process may be responsible for the formation of N-MWCNTs.

Deep learning-enabled analysis reveals distinct neuronal phenotypes induced by aging and cold-shock

BackgroundAccess to quantitative information is crucial to obtain a deeper understanding of biological systems. In addition to being low-throughput, traditional image-based analysis is mostly limited to error-prone qualitative or semi-quantitative assessment of phenotypes, particularly for complex subcellular morphologies. The PVD neuron in Caenorhabditis elegans, which is responsible for harsh touch and thermosensation, undergoes structural degeneration as nematodes age characterized by the appearance of dendritic protrusions. Analysis of these neurodegenerative patterns is labor-intensive and limited to qualitative assessment.ResultsIn this work, we apply deep learning to perform quantitative image-based analysis of complex neurodegeneration patterns exhibited by the PVD neuron in C. elegans. We apply a convolutional neural network algorithm (Mask R-CNN) to identify neurodegenerative subcellular protrusions that appear after cold-shock or as a result of aging. A multiparametric phenotypic profile captures the unique morphological changes induced by each perturbation. We identify that acute cold-shock-induced neurodegeneration is reversible and depends on rearing temperature and, importantly, that aging and cold-shock induce distinct neuronal beading patterns.ConclusionThe results of this work indicate that implementing deep learning for challenging image segmentation of PVD neurodegeneration enables quantitatively tracking subtle morphological changes in an unbiased manner. This analysis revealed that distinct patterns of morphological alteration are induced by aging and cold-shock, suggesting different mechanisms at play. This approach can be used to identify the molecular components involved in orchestrating neurodegeneration and to characterize the effect of other stressors on PVD degeneration.

Molecular Mechanisms of Ferroptosis and Its Role in Pulmonary Disease.

Ferroptosis is a new mode of cell death that is characterized by the excessive accumulation of iron and lipid peroxides. It has unique morphological changes and disparate biochemical features and plays an intricate role in many pathophysiological processes. A great deal of researches confirms that ferroptosis can be regulated by numerous molecules through different mechanisms, supporting great potentials for novel pharmacological therapeutics. Recently, several studies reveal that ferroptosis is also closely associated with the initiation and development of respiratory disease. Understanding the specific mechanism, the molecular trait of ferroptosis and their relationship with pulmonary disease could provide significant references regarding effective treatment of these obstinate disease.

Multiscale Simulation for the Initial Stage of the Zn Electrodeposition with Kinetic Monte Carlo Based on First-Principle Calculation

Zn negative electrodes for the secondary battery are attractive for the grid-scale energy storage. One of the main issues for its application is a morphological change of Zn during the electrodeposition on the cathode. In particular, formation mechanism of the mossy structure has not been clarified yet. Our previous study observed the layer-like Zn deposits before the evolution of the mossy structure[1]. However, cause of the layer-like structure is still unclear. To reveal further detailed mechanism, molecular level understanding is significant. Kinetic Monte Carlo (KMC) simulation with first-principle calculation is a powerful tool to analyze the morphological formation from the molecular level. This study analyses the initial stage of the Zn electrodeposition by KMC with the parameters derived from first-principle calculations to provide insights into the cause of the unique morphological changes of Zn.In the KMC simulation code, the surface diffusion and deposition were taken into account. (a) surface diffusion on pure facets, (b) edge diffusion along islands, (c) interlayer diffusion were included as the surface diffusion events. All surface diffusion rates were estimated by the transition state theory from first principle calculations. The deposition rate corresponds to current density set in the actual electrochemical measurements. First-principle calculations with the solvation were performed by Vienna ab initio simulation package (VASP) with the polarized continuum model (PCM) and Quantum-ESPRESSO code with the effective screening medium + the reference interaction site model (ESM-RISM)[2]. ESM-RISM can describe the electrochemical interface with the applied potential and the surrounding electrolyte. Nudged elastic band was used to calculate the transition state. Cu(111) and Zn(0001) were utilized as a typical substrate species.The transition state of the surface diffusion of the Zn adatom on Cu(111) and Zn(0001) were calculated in the gas phase initially. The activation energy on Cu was much higher than on Zn, which were 4.38 and 0.58 kJ/mol, respectively. This tendency showed a good agreement with the general discussion of the surface diffusion[3]. To realize the solvation effects on each surface, transition state of the surface diffusion with PCM were calculated. The activation energy on Cu(111) was 4.79 kJ/mol, which was 0.41 kJ/mol higher than the gas phase. On the other hand, the activation energy on Zn(0001) in solvent was only 0.19 kJ/mol higher than the gas phase. The Zn adatom behavior was affected by not only the simple solvation but the interfacial structure among the adatom, solvents and surfaces, indicating that the interaction between the surfaces and solvent species is a significant factor for the surface diffusion behavior. These differences could derive from the difference of the surface electronic state. Since the surface electronic state depends on the facets, the interfacial interaction would affect and change the balance of the surface diffusion among the facets. This effect will cause the change of the initial deposition behavior. Combining these activation energies with KMC as the parameters, we could find the relationship between the morphological features of metals and the electronic state of the surface.Fig. The transition state of the surface diffusion of the Zn adatom in gas and solvent phases[1] T. Otani, Y. Fukunaka, T. Homma, Electrochim. Acta, 242, 364-372 (2017).[2] S. Nishihara, M. Otani, Phys. Rev. B, 96, 115429-115433 (2017).[3] K. Iokibe, K. Azumi, H. Tachikawa, J. Phys. Chem. C, 111, 13510-13516 (2007). Figure 1

Morphological adjustment in free-living Steinernema feltiae infective juveniles to increasing concentration of Nemafric-BL phytonematicide.

Third-stage larvae (L3) of Steinernema feltiae exist as free-living infective juveniles (IJ), with suspended development activities. In contrast, parasitic stages (L1, L2, L4, adult) have mutualistic relations with Xenorhabdus species bacteria, along with unique morphological changes and development inside the cadaver of host insects and/or plant-parasitic nematodes. Commercial IJ strains are tolerant to cucurbitacin-containing phytonematicides, but we have scant information on how morphological adjustments in IJ are achieved. In this study, we investigated the nature of morphological adjustments in commercial S. feltiae IJ strains to Nemafric-BL phytonematicide, which contains cucurbitacin B as active ingredient. Post-72 h exposure to phytonematicide concentration, IJ specimens were fixed on mounting slides. Length (body, excretory pore to anterior end, pharynx, rectum, stoma, tail), diameter (head width, neck base, mid-body, anal body), cuticle thickness and De Man ratios were measured with a computer software programme attached to Omax light microscope. Morphometric data against increasing phytonematicide concentration exhibited either density-dependent quadratic, linear or neutral relations. Increase in body length at low phytonematicide concentration was accompanied by decrease in tail length and pharynx length during muscle contraction when IJ were still alive. After death at high phytonematicide concentration, the opposite morphometric effects ensued due to muscle relaxation. The observed changes in morphometric structures were explained on the basis of morphological adjustments that modulated volumes of pseudocoelom cavity in IJ. The modulation is intended to maintain hydrostatic pressure within permissible upper limits in order to avoid structural damage to internal organs embedded in the pseudocoelom fluids.

Cytopathological Diagnosis of Herpes Simplex Viral Mastitis: Three Rare Cases and a Review of the Literature.

Context:Virus infection has a unique morphological change in cell pathology. It is also of great significance in the diagnosis of herpes simplex mastitis.Aims:To evaluate the practicability and feasibility of cytological diagnosis of herpes simplex virus mastitis.Materials and Methods:Three cases of HSV mastitis diagnosed by cytology smears were collected. The papules were stained with Wright-Giemsa to observe the morphological characteristics of the cells.Statistical Analysis:The cytological characteristics of 3 cases were summarized and compared with the literature.Results:In the background of inflammatory cells in the smear, the cells with characteristic changes can be seen in the mass and scattered distribution. The nuclear size increased significantly, and mononuclear, binuclear, trinuclear and multinuclear nuclei appeared. The nuclei of multinuclear were crowded and mosaic. The chromatin of nucleus changed like frosted glass, and the chromatin became thicker at the edge of nucleus. Inclusion bodies were found in the nucleus, eosinophilic, with different sizes and irregular shapes. These characteristics are helpful to distinguish from other lesions.Conclusion:Scraper cytology is a diagnostic tool with simple operation, small trauma and pain, and it has important application value in the differential diagnosis of HSV infection, which deserves the attention of clinicians.

A Pilot Optical Coherence Tomography Angiography Study on Superficial and Deep Capillary Plexus Foveal Avascular Zone in Patients With Beta-Thalassemia Major

To investigate foveal avascular zone (FAZ) changes in the superficial (SCP) and deep (DCP) capillary plexuses in beta-thalassemia major (BTM) patients, as shown in optical coherence tomography angiography. Nonrandomized, comparative case series of 54 eyes of 27 BTM patients and 46 eyes of 23 healthy controls, utilizing an automated FAZ detection algorithm. Measurements included FAZ area and FAZ shape descriptors (convexity, circularity, and contour temperature). Results were compared between the two groups, and correlated to iron load and chelation therapy parameters. SCP and DCP FAZ area were not significantly different between the control and BTM groups (P = 0.778 and P = 0.408, respectively). The same was true regarding SCP FAZ convexity (P = 0.946), circularity (P = 0.838), and contour temperature (P = 0.907). In contrast, a statistically significant difference was detected between controls and BTM group regarding DCP FAZ convexity (P = 0.013), circularity (P = 0.010), and contour temperature (P = 0.014). Desferrioxamine dosage was strongly correlated to the DCP area (r = 0.650, P = 0.05) and liver magnetic resonance imaging/T2-star to DCP circularity (r = -0.492, P = 0.038). Correlations were also revealed between urine Fe excretion and DCP convexity (r = 0.531, P = 0.019), circularity (r = 0.661, P = 0.002), and contour temperature (r = -0.591, P = 0.008). Retinal capillary plexuses and especially DCP seem to present unique morphologic changes in BTM patients, not in the FAZ area, but in specific shape descriptors, indicating minor but detectable FAZ changes. These changes correlate well with iron load and chelation therapy parameters. Their clinical importance and pathophysiologic implications remain to be elucidated through further studies.

Morphology-based classification of mycobacteria-infected macrophages with convolutional neural network: reveal EsxA-induced morphologic changes indistinguishable by naked eyes

EsxA is an essential virulence factor for Mycobacterium tuberculosis (Mtb) pathogenesis as well as an important biomarker for Mtb detection. In this study, we use light microscopy and deep learning-based image analysis to classify the morphologic changes of macrophages infected by Mycobacterium marinum (Mm), a surrogate model for Mtb. Macrophages were infected either with the mCherry-expressing Mm wild type strain (Mm(WT)), or a mutant strain with deletion of the esxA-esxB operon (Mm(ΔEsxA:B)). The mCherry serves as an infection marker to train the convolution neural network (CNN) and to validate the classification results. Data show that CNN can distinguish the Mm(WT)-infected cells from uninfected cells with an accuracy of 92.4% at 2 hours postinfection (hpi). However, the accuracy at 12 and 24 hpi is decreased to ∼75% and ∼83%, respectively, suggesting dynamic morphologic changes through different stages of infection. The accuracy of discriminating Mm(ΔEsxA:B)-infected cells from uninfected cells is lower than 80% at all time, which is consistent to attenuated virulence of Mm(ΔEsxA:B). Interestingly, CNN distinguishes Mm(WT)-infected cells from Mm(ΔEsxA:B)-infected cells with ∼90% accuracy, implicating EsxA induces unique morphologic changes in macrophages. Deconvolutional analysis successfully reconstructed the morphologic features used by CNN for classification, which are indistinguishable to naked eyes and distinct from intracellular mycobacteria. This study presents a deep learning-aided imaging analytical tool that can accurately detect virulent mycobacteria-infected macrophages by cellular morphologic changes. The observed morphologic changes induced by EsxA warrant further studies to fill the gap from molecular actions of bacterial virulence factors to cellular morphology.

Infection-Induced Peroxisome Biogenesis Is a Metabolic Strategy for Herpesvirus Replication

Viral proteins have evolved to target cellular organelles and usurp their functions for virus replication. Despite the knowledge of these critical functions for several organelles, little is known about peroxisomes during infection. Peroxisomes are primarily metabolic organelles with important functions in lipid metabolism. Here, we discovered that the enveloped viruses human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) induce the biogenesis of and unique morphological changes to peroxisomes to support their replication. Targeted proteomic quantification revealed a global virus-induced upregulation of peroxisomal proteins. Mathematical modeling and microscopy structural analysis show that infection triggers peroxisome growth and fission, leading toincreased peroxisome numbers and irregular disc-like structures. HCMV-induced peroxisome biogenesis increased the phospholipid plasmalogen, thereby enhancing virus production. Peroxisome regulation and dependence were not observed for the non-enveloped adenovirus. Our findings uncover a role of peroxisomes in viral pathogenesis, with likely implications for multiple enveloped viruses.