Small Cells Research Articles

Simultaneous degradation of cyanobacteria and cyanotoxins by catalytic wet peroxide oxidation: Impact of morphology and growth stage

The widespread proliferation of potentially toxic cyanobacteria in source waters for drinking water treatment plants (DWTPs) presents a pressing contemporary challenge. Although catalytic wet peroxide oxidation (CWPO) has been recognized as a highly effective and environmentally friendly technology for removing cyanotoxins from water, the simultaneous degradation of cyanobacteria and cyanotoxins has been scarcely investigated. Considering their great morphological diversity, in this work, the impact of the presence of pure strains of several species of toxic and non-toxic cyanobacteria on the degradation of relevant cyanotoxins has been evaluated considering also the main stages of their life cycle. In each studied scenario, achieving a full eradication of the cyanobacteria also led to the complete elimination of the cyanotoxin, including both intra and extracellular fractions. Morphological factors, including filament and cell sizes, play a crucial role in the efficiency of the process. Small cells and long filaments entail a higher presence of particulate organic matter, which consumes hydroxyl radicals considerably in competence with the cyanotoxin degradation. Moreover, the growth stage emerges as a pivotal factor in understanding the CWPO process performance, with cyanobacteria in their early life stages, exhibiting more pronounced interference compared to later stages, probably due to their higher cell viability and accelerated metabolism. All these understandings are essential for the successful implementation of the technology in treating surface waters affected by toxic cyanobacterial blooms.

Spectroscopy-Guided Discovery of Three-Dimensional Structures of Disordered Materials with Diffusion Models

Abstract Spectroscopy techniques such as X-ray absorption near edge structure (XANES) provide valuable insights into the atomic structures of materials, yet the inverse prediction of precise structures from spectroscopic data remains a formidable challenge. In this study, we introduce a framework that combines generative artificial intelligence (AI) models with XANES spectroscopy to predict three-dimensional atomic structures of disordered systems, using amorphous carbon ($a$-C) as a model system. In this work, we introduce a new framework based on the diffusion model, a recent generative machine learning method, to predict 3D structures of disordered materials from a target property.For demonstration, we apply the model to identify the atomic structures of $a$-C as a representative material system from the target XANES spectra. We show that conditional generation guided by XANES spectra reproduces key features of the target structures. Furthermore, we show that our model can steer the generative process to tailor atomic arrangements for a specific XANES spectrum. Finally, our generative model exhibits a remarkable scale-agnostic property, thereby enabling generation of realistic, large-scale structures through learning from a small-scale dataset (i.e., with small unit cells). Our work represents a significant stride in bridging the gap between materials characterization and atomic structure determination; in addition, it can be leveraged for materials discovery in exploring various material properties as targeted.

The Tmem16a chloride channel is required for mucin maturation after secretion from goblet-like cells in the Xenopus tropicalis tadpole skin

The TMEM16A chloride channel is proposed as a therapeutic target in cystic fibrosis, where activation of this ion channel might restore airway surface hydration and mitigate respiratory symptoms. While TMEM16A is associated with increased mucin production under stimulated or pro-inflammatory conditions, its role in baseline mucin production, secretion and/or maturation is less well understood. Here, we use the Xenopus tadpole skin mucociliary surface as a model of human upper airway epithelium to study Tmem16a function in mucus production. We found that Xenopus tropicalis Tmem16a is present at the apical membrane surface of tadpole skin small secretory cells that express canonical markers of mammalian “goblet cells” such as Foxa1 and spdef. X. tropicalis Tmem16a functions as a voltage-gated, calcium-activated chloride channel when transfected into mammalian cells in culture. Depletion of Tmem16a from the tadpole skin results in dysregulated mucin maturation post-secretion, with secreted mucins having a disrupted molecular size distribution and altered morphology assessed by sucrose gradient centrifugation and electron microscopy, respectively. Our results show that in the Xenopus tadpole skin, Tmem16a is necessary for normal mucus barrier formation and demonstrate the utility of this model system to discover new biology relevant to human mucosal biology in health and disease.

Three-dimensional dynamics of unstable lean premixed hydrogen-air flames: Intrinsic instabilities and morphological characteristics

The 3D swinging laser sheet technique was employed to study the development and morphological characteristics of premixed hydrogen-air unstable flames in a spherical explosion vessel. Pressure dependencies for laminar flame propagation were sought to exploit the role of the Darrieus-Landau (DL) and Thermal-diffusive (TD) instabilities in the unstable self-accelerating flame regime. A sufficiently low Markstein number, as a consequence of the increased pressure, leads to more cracking and smaller cells over the flame surface. The degree of wrinkling on the flame surface is proportional to the increase in flame burning velocity, a relationship that holds true for low pressures but is not applicable under high pressures. External turbulence can significantly alter the extent of flame surface wrinkling even at low root mean square velocities, producing a more wrinkled flame surface compared to intrinsic cellularity, and distinctly affecting flame dynamics. The increased wrinkling and flame speed due to external turbulence can be attributed to the synergistic effects between thermo-diffusive instabilities and turbulence, resulting in higher fuel consumption rates per flame surface area and the formation of finger-like structures that enhance flame displacement speed in curved segments. The parameters, ϵ, deviation of the Lewis number from a critical value, and ω2, obtained through classical linear stability analysis, display a clear linear relationship with the ratio of the wrinkled surface area observed in planar flames. This study enhances the understanding of hydrogen flame instabilities, which is crucial for preventing explosions in hydrogen storage and utilization, and provides valuable insights into flame dynamics, supporting the design of safer and more efficient hydrogen-fueled engines and turbines.

An aggressive gastric CIC-DUX4 sarcoma surgically resected with multivisceral organs: a case report

BackgroundCapicua transcriptional repressor-double homeobox 4 sarcoma (CDS) is a rare and aggressive malignant soft tissue tumor that typically arises within the soft tissues. We report an exceptionally rare case of a gastric CDS successfully resected despite its extensive invasion into surrounding organs.Case presentationA 48-year-old male presented with a progressively enlarging abdominal mass. Upper gastrointestinal endoscopy revealed a large ulcerative tumor on the posterior gastric wall. Biopsy results initially suggested a neuroendocrine cell carcinoma. Contrast-enhanced computed tomography showed a 20 cm tumor protruding from the posterior stomach wall, directly invading the pancreas and colon. We performed a multivisceral resection (stomach, pancreatic tail, spleen, and transverse colon) achieving an R0 resection. Pathological examination of the permanent specimen revealed small round cells with high nuclear-to-cytoplasmic ratios. Immunohistochemical staining confirmed the diagnosis of CDS. The patient recovered well and was discharged on postoperative day 33.ConclusionsThis case report describes the first detailed account of a surgically resected aggressive CDS originating from the stomach.

High-order accurate implicit-explicit time-stepping schemes for wave equations on overset grids

New implicit and implicit-explicit time-stepping methods for the wave equation in second-order form are described with application to two and three-dimensional problems discretized on overset grids. The implicit schemes are single step, three levels in time, and based on the modified equation approach. Second and fourth-order accurate schemes are developed and they incorporate upwind dissipation for stability on overset grids. The fully implicit schemes are useful for certain applications such as the WaveHoltz algorithm for solving Helmholtz problems where very large time-steps are desired. Some wave propagation problems are geometrically stiff due to localized regions of small grid cells, such as grids needed to resolve fine geometric features, and for these situations the implicit time-stepping scheme is combined with an explicit scheme: the implicit scheme is used for component grids containing small cells while the explicit scheme is used on the other grids such as background Cartesian grids. The resulting partitioned implicit-explicit scheme can be many times faster than using an explicit scheme everywhere. The accuracy and stability of the schemes are studied through analysis and numerical computations.

Valproic acid alleviates total-body irradiation-induced small intestinal mucositis in mice

Purpose Gastrointestinal (GI) injury is one of the serious problems of total-body irradiation (TBI). However, no fundamental treatment for TBI and other radiation-induced GI injury has yet been established. Valproic acid (VPA) administration reduces mortality in mice subjected to total-body irradiation (TBI) with X-rays. This study aimed to evaluate the effects of VPA on GI injury induced by TBI in mice. Materials and methods Mice were subjected to TBI with X-rays to induce GI injury. Changes in survival and weight were observed after VPA administration. The small intestine was then sampled at 0, 1, 3, 7, and 10 d after irradiation for histological and immunohistological evaluation and measurement of myeloperoxidase (MPO) activity and inflammatory cytokine levels (IL-1β). Results VPA (200 and 600 mg/kg) increased survival rate and reduced weight loss in model mice. IL-1β expression 1 d after irradiation was significantly lower in the VPA group than that in the vehicle group. Furthermore, the increase in MPO activity at 3 and 7 d after irradiation was significantly suppressed by VPA administration. Histological examination (hematoxylin and eosin staining) revealed that 600 mg/kg VPA inhibited inflammatory cell infiltration. Immunostaining for the proliferating cell nuclear antigen involved in cell proliferation showed that VPA suppressed the irradiation-induced decrease in cell proliferative capacity. Conclusions Treatment with VPA in mice with GI injury caused by TBI suppressed inflammatory responses in small intestinal mucosal cells. These results suggest that VPA may be a useful therapeutic agent against TBI-induced small intestinal mucositis.

Small archaea may form intimate partnerships to maximize their metabolic potential.

DPANN archaea have characteristically small cells and unique genomes that were long overlooked in diversity surveys. Their reduced genomes often lack essential metabolic pathways, requiring symbiotic relationships with other archaeal and bacterial hosts for survival. Yet a long-standing question remains, what is the advantage of maintaining ultrasmall cells. A recent study by Zhang et al. examined genomes of DPANN archaea from marine oxygen deficient zones (ODZs) (I. H. Zhang, B. Borer, R. Zhao, S. Wilbert, et al., mBio 15:e02918-23, 2024, https://doi.org/10.1128/mbio.02918-23). Surprisingly, these genomes contain a broad array of metabolic pathways including genes predicted to be involved in nitrous oxide (N2O) reduction. However, N2O levels are likely too low in ODZs to make this metabolically feasible. Modeling co-localization of DPANN archaea (N2O consumers) with other larger cells (N2O producers) demonstrates that N2O uptake rates can be optimized by maximizing the producer-to-consumer size ratio and proximity of consumer cells to producers. This may explain why such a diversity of archaea maintain extremely small cell sizes.

Mycobacterium avium inhibits protein kinase C and MARCKS phosphorylation in human cystic fibrosis and non-cystic fibrosis cells.

In cystic fibrosis (CF), there is abnormal translocation and function of the cystic fibrosis transmembrane conductance regulator (CFTR) and an upregulation of the epithelial sodium channel (ENaC). This leads to hyperabsorption of sodium and fluid from the airway, dehydrated mucus, and an increased risk of respiratory infections. In this study, we performed a proteomic assessment of differentially regulated proteins from CF and non-CF small airway epithelial cells (SAEC) that are sensitive to Mycobacterium avium. CF SAEC and normal non-CF SAEC were infected with M. avium before the cells were harvested for protein. Protein kinase C (PKC) activity was greater in the CF cells compared to the non-CF cells, but the activity was significantly attenuated in both cell types after infection with M. avium compared to vehicle. Western blot and densitometric analysis showed a significant increase in cathepsin B protein expression in M. avium infected CF cells. Myristoylated alanine rich C-kinase substrate (MARCKS) protein was one of several differentially expressed proteins between the groups that was identified by mass spectrometry-based proteomics. Total MARCKS protein expression was greater in CF cells compared to non-CF cells. Phosphorylation of MARCKS at serine 163 was also greater in CF cells compared to non-CF cells after treating both groups of cells with M. avium. Taken together, MARCKS protein is upregulated in CF cells and there is decreased phosphorylation of the protein due to a decrease in PKC activity and presumably increased cathepsin B mediated proteolysis of the protein after M. avium infection.

Teratoid hepatoblastoma with small cell undifferentiated histology in polysplenia patient: a case report

Abstract Introduction/Objective Hepatoblastoma (HB) with teratoid is a uncommon variant of mixed epithelial and mesenchymal components. Conversely, HB with small cell undifferentiated (SCUD) is extremely rare, with only nine documented cases showing retained INI-1 expression in the literature. The prognosis of SCUD remains debatable. In this report, we describe the first case of combined teratoid HB with a SCUD component that preserved INI-1 expression with a favorable outcome. Methods/Case Report A 2-year-old girl with polysplenia syndrome presented with a right liver mass detected during ultrasound screening. The alpha fetoprotein levels were significantly elevated to 148,000. MRI revealed a 7.2 cm lesion, staged as Pre-Treatment Extent 2 (PRETEXT) in the right anterior liver. She underwent cholecystectomy and right hepatectomy. Resection specimen revealed a mixed neoplasm comprising epithelial components (fetal and embryonal) and mesenchymal components. Additionally, notable findings include small cell component and teratoid features, characterized by melanin pigment and neuroectodermal elements. All the neoplastic cells showed reactivity with CD34, reticulin, SALL4, beta-catenin, GPC-3, arginase-1, chromogranin, and glutamine synthetase. Notably, the teratoid area only displayed positivity for CD56 and NSE, while vimentin highlighted capillaries, vessels and focally staining small cells. Furthermore, CK19 highlighted the small cell components and the bile ducts in the background liver. Importantly, INI-1 staining was retained in all tumor cells, including the small cell component. Synaptophysin and Prussian blue were negative in all lesional cells. After a 2-year follow-up, no recurrence was observed. Results (if a Case Study enter NA) NA Conclusion This case underscores the diagnostic challenge posed by small cell undifferentiated (SCUD) hepatoblastoma. Moreover, it contributes to the understanding of this rare variant of hepatoblastoma and suggests a potential favorable prognosis associated with retained INI-1 staining in the SCUD component.

Epstein Barr Virus Positive Mucocutaneous Ulcer versus Classic Hodgkin Lymphoma: Challenges in Diagnosis

Abstract Introduction/Objective Epstein- Barr virus positive mucocutaneous ulcer (EBVMCU) is a clinicopathologic entity first identified in 2010. It occurs in patients with immunosuppression and presents as a well circumscribed ulceration on the oropharyngeal mucosa, skin or gastrointestinal tract. Infiltrates of atypical lymphoid cells that may have appearances similar to Diffuse Large B-cell Lymphoma (DLBCL) or Classic Hodgkin Lymphoma (CHL) are seen. Methods/Case Report A 41 year old male patient with history of HIV infection presented with hematochezia and rectal pain, underwent sigmoidoscopy and a large ulcerated mass was present at the anal verge. Polymorphic infiltrates of small lymphoid cells, eosinophils, granulocytes, plasma cells, histiocytes and scattered large atypical lymphoid cells, morphologically mimicking Reed-Sternberg cells were identified. The large atypical lymphoid cells were positive for CD30, MUM-1, BCL-6, EBER (EBV) and negative for CD3, CD15, CD20, CD45, CD79a, SOX-10. Based on lack of B-symptoms, no lymphadenopathy, superficial lesions, reduced CD4/CD8 ratio and specific location, EBVMCU was favored. Eight months later, he presented with night sweats, decreased appetite and inguinal lymphadenopathy. Lymph node excision displayed infiltrates of predominantly small lymphocytes, histiocytes, plasma cells and eosinophils. Foci of scattered large atypical cells morphologically compatible with Hodgkin/Reed Sternberg cells with focal necrosis were noted. The atypical cells were positive for CD30, PAX5 (weak), CD20 (subset), CD15 (focal), MUM-1 and EBV-EBER. CHL, Mixed Cellularity Subtype was diagnosed. Results (if a Case Study enter NA) NA Conclusion As a newer entity, we don’t know if EBVMCU can co-exist with or progress to CHL/DLBCL. Therefore, EBVMCU patients should undergo vigilant screening.

Clinicopathological Characteristics of Small Cell Carcinoma of the Ovary, Hypercalcemic Type – a case Series

Abstract Introduction/Objective Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare (<0.01%) and aggressive ovarian tumor primarily affecting young women (median of approximately 24 years), characterized by rapid growth, early metastasis, and association with hypercalcemia in two-thirds of cases. The diagnosis of SCCOHT is challenging due to its rarity and lack of specific clinical symptoms or biomarkers. Our study aims to delineate the clinicopathologic characteristics of SCCOHT based on our case series and add to the existing knowledge. Methods/Case Report A retrospective review of University of Pennsylvania Health system pathology database was conducted from 2012 to 2024. Our study identified four patients diagnosed with SCCOHT. Clinical information and histopathologic characteristics were reviewed. Results (if a Case Study enter NA) Among the four patients identified, the median age was 24 years, with a median tumor size of 14.5 cm, and all patients presented with weight loss, abdomen bloating, and elevated CA125 levels. Notably, two patients exhibited hypercalcemia, while one initially presented with normal calcium levels but developed hypercalcemia during disease recurrence. One patient maintained normal calcium levels throughout. Surgical intervention involved bilateral salpingo-oophorectomy in all cases, with pathological staging revealing two patients at pT1a, one at pT1c, and one at pT3c. Histopathological analysis consistently revealed similar morphology, including solid and cystic necrotic neoplasms with diffuse growth or nests/cords of undifferentiated small cells, which displaying vesicular chromatin and prominent nucleoli. Immunohistochemical staining demonstrated loss of BRG1 (SMARCA4) expression in two patients and diffuse positivity for WT1 in all patietns, while negative for cytokeratin, germ cell markers, and melanocytic markers. Genetic test revealed SMARCA4 mutation (p.E 717*, c.3169-1G>A) in one patient. Conclusion Small cell carcinoma of the ovary, hypercalcemic type, presents a diagnostic and therapeutic challenge due to its rarity and aggressive nature. Adequate treatment options are currently limited, highlighting the critical need for further research and development of targeted therapies in SCCOHT. Testing for mutations in the SMARCA4 gene is essential for accurate diagnosis of SCCOHT and may uncover new avenues for treatment and management strategies.

CK20-negative Merkel Cell Carcinoma with Concomitant Squamous Cell Carcinoma In-Situ and Metastasis to the Parotid Gland

Abstract Introduction/Objective This report presents a patient with an aggressive CK20-negative neuroendocrine tumor of the dermis with metastasis to the parotid gland and a concomitant squamous cell carcinoma in-situ (SCCIS) and highlights diagnostic challenges of CK20-negative tumors. Methods/Case Report A centennial female with a history of non-melanoma skin cancer and leukemia presented to the dermatology clinic with a one-year history of an enlarging skin lesion on her right cheek and a subcutaneous mass on the right central lateral neck. On examination, the lesion appeared as a rough and raised red papule with a central crust. On CT, a large heterogeneously enhancing right parotid mass with surrounding satellite nodules, adjacent necrotic adenopathy, and an ulcerating subcutaneous mass in the adjacent right face. An incidental 3 mm right upper lobe nodule was identified. The pathology report noted two distinct malignant neoplasms within the specimen. Microscopy revealed ulceration with acanthosis and full thickness keratinocyte atypia, suggesting Bowen’s disease. On microscopic examination of the separate dermal tumor, there were sheets of uniform small cells with a high nuclear to cytoplasmic ratio and scant cytoplasm. IHC staining was positive for the neuroendocrine markers AE1/AE3, CAM5.2, synaptophysin, and CD56. CK20, CK7, and TTF-1 were negative. As some MCC may be negative for CK20, CK20 was performed twice. Differential diagnoses included SCCIS with CK20-negative MCC versus a metastatic neuroendocrine carcinoma of parotid gland to the skin. The patient transitioned to hospice care soon after the diagnosis. Results (if a Case Study enter NA) NA. Conclusion Our patient presents with an interesting case of a CK20-negative MCC with metastasis to the parotid gland. Since CK20 was stained negative twice, it complicated the diagnosis of MCC vs. small cell carcinoma. We suspected a more likely diagnosis of MCC metastasis to the parotid gland due to multiple reported cases (Day et al. 2016). Our patient also had an identifiable Bowen’s disease borderline to the neuroendocrine carcinoma. It is well known of the coexistence of MCC and squamous cell carcinoma in a cutaneous lesion (Suaiti et al. 2019). Thus, a metastatic MCC to the parotid gland is more likely in this case. As MCC is an aggressive cancer that metastasizes quickly, accurate diagnosis is crucial. With recent literature reporting the association of CK20-negativity with VN-MCC, and the presence of UV signature mutations in CK20- negative MCC, genomic screening would be a useful diagnostic tool.

Isolated intracranial myeloid sarcoma as an acute myeloid leukemia relapse: A case report

Abstract Introduction/Objective Adequate assessment during intraoperative consultation on a patient with a brain mass is imperative to provide critical information that will direct the therapeutic approach during surgery. Methods/Case Report The patient is a 67-year-old female with acute myeloid leukemia (AML) on maintenance therapy and in remission for the past 2 years that developed altered mental status and seizures. Imaging revealed a diffuse intra-axial mass within the corpus callosum and right hypothalamic region. A brain stereotactic biopsy was performed. Blood work showed mild leukopenia (3.63x109/L), thrombocytopenia (platelet count of 82x109/L), and an essential normal hemoglobin level of 11.9 g/dL. A frozen section assessment during intraoperative consultation revealed an infiltration of small blue cells, suggesting a hematolymphoid process. Further histological assessment showed small to intermediate-sized monomorphic cells in sheets and around the vessels with open fine chromatin, prominent nuclei, and scant cytoplasm admixed with tingible body macrophages. Differential diagnoses included high- grade B-cell lymphoma, Burkitt lymphoma, mantle cell lymphoma blastoid variant, lymphoblastic lymphoma, and myeloid sarcoma (MS). The tumor cells were positive for CD34, CD43, and MPO (subset) and negative for CD20, PAX5, TdT, CD3, and AE1/AE3 by immunohistochemical staining, consistent with MS. Concurrent bone marrow biopsy with flow cytometric evaluation showed progressive trilineage hematopoiesis without evidence of residual leukemia. Results (if a Case Study enter NA) NA Conclusion Intracranial MS is extremely rare, and literature reviews are limited to primarily case reports. MS can occur before, during, or after the initial presentation of AML. Interestingly, this patient had an isolated intracranial myeloid sarcoma as an AML relapse without bone marrow involvement. We aim to increase the awareness of isolated recurrence of AML in the form of an intracranial MS; this disease warrants consideration in patients with a history of a myeloid neoplasm who present with neurological symptoms despite the absence of peripheral disease.

Pseudolipoblastic Perineuroma: A Rare Histologi̇c Subtype.

Pseudolipoblastic perineurioma is a very uncommon variant of extraneural perineurioma, with only a limited number of cases documented in the medical literature. The most remarkable histopathologic characteristic is the existence of vacuolated cells that closely resemble lipoblasts; besides the presence of small, spindle shaped, or epithelioid perineurial cells. In this study, we present another case of pseudolipoblastic perineurioma, predominantly characterized by the presence of vacuolated "pseudolipoblastic" cells. The immunohistochemical expression of EMA, Glut-1, claudin-1, collagen type IV, and laminin as well as S-100 negativity is essential for the diagnosis to support the perineurial origin. Simple excision is the best treatment option for these benign tumors that do not recur or metastasize. It is crucial to recognize this rare entity to differentiate it from many other tumors characterized by prominent intracytoplasmic vacuoles.

Adenoma, Hamartoma, or Something Else? Unique Diagnostic Challenges in Mixed Epithelial-Mesenchymal Lesions of the Gastrointestinal Tract

Abstract Introduction/Objective Mixed epithelial-mesenchymal lesions (MEMLs) are well-known in the gynecologic tract and, to a lesser extent, in the lungs and kidneys. However, the literature is mostly lacking in the GI tract. These cases pose significant diagnostic challenge when encountered upon, as there are many pitfalls and gray areas exist in characterization. Amongst other entities, hamartomas can account for a portion of these cases. Herein, we present a unique case of MEML identified in duodenum, which was reported as a hamartoma. Methods/Case Report A 59-year-old male presented with persistent upper GI bleeding requiring multiple transfusions. Initial upper GI endoscopy revealed an oozing ulcer as part of a 30 mm polyp in the second portion of duodenum opposite to ampulla. Epinephrine was injected for homeostasis. After repeat endoscopy failed to completely resect the lesion, the patient underwent exploratory laparotomy with resection of the 2nd portion of duodenum. The sections showed a submucosal proliferation of epithelial and mesenchymal elements. The epithelial component consisted of bland-appearing foveolar type mucinous glands, partly showing cystic dilation, while the mesenchymal component consisted of lymphovascular and neural structures as well as a population of small round cells that showed patchy SMA immunolabeling and low Ki67 proliferation index. The case was reported as hamartoma, however, a Brunner’s gland cyst and pericytic tumors (i.e. glomus tumor) were also considered. While the histologic features did not suggest malignancy, the patient had been followed-up closely for 6 months. Recurrence or malignant transformation was not reported. Results (if a Case Study enter NA) NA Conclusion MEMLs in the GI tract are always challenging to diagnose due to their rarity, unknown etiology and natural history, and lack of established risk factors. Furthermore, mesenchymal component is often difficult to characterize due to multiple differentiations and patchy/unrevealing immunohistochemistry. We report this unique case to enhance the awareness and recognition of MEMLS in the GI tract.

Assessing tumor microstructure with time-dependent diffusion imaging: Considerations and feasibility on clinical MRI and MRI-Linac.

Quantitative imaging biomarkers (QIBs) can characterize tumor heterogeneity and provide information for biological guidance in radiotherapy (RT). Time-dependent diffusion MRI (TDD-MRI) derived parameters are promising QIBs, as they describe tissue microstructure with more specificity than traditional diffusion-weighted MRI (DW-MRI). Specifically, TDD-MRI can provide information about both restricted diffusion and diffusional exchange, which are the two time-dependent effects affecting diffusion in tissue, and relevant in tumors. However, exhaustive modeling of both effects can require long acquisitions and complex model fitting. Furthermore, several introduced TDD-MRI measurements can require high gradient strengths and/or complex gradient waveforms that are possibly not available in RT settings. In this study, we investigated the feasibility of a simple analysis framework for the detection of restricted diffusion and diffusional exchange effects in the TDD-MRI signal. To promote the clinical applicability, we use standard gradient waveforms on a conventional 1.5 T MRI system with moderate gradient strength (Gmax=45 mT/m), and on a hybrid 1.5 T MRI-Linac system with low gradient strength (Gmax=15 mT/m). Restricted diffusion and diffusional exchange were simulated in geometries mimicking tumor microstructure to investigate the DW-MRI signal behavior and to determine optimal experimental parameters. TDD-MRI was implemented using pulsed field gradient spin echo with the optimized parameters on a conventional MRI system and a MRI-Linac. Experiments in green asparagus and 10 patients with brain lesions were performed to evaluate the time-dependent diffusion (TDD) contrast in the source DW-images. Simulations demonstrated how the TDD contrast was able to differentiate only dominating diffusional exchange in smaller cells from dominating restricted diffusion in larger cells. The maximal TDD contrast in simulations with typical cancer cell sizes and in asparagus measurements exceeded 5% on the conventional MRI but remained below 5% on the MRI-Linac. In particular, the simulated TDD contrast in typical cancer cell sizes (r=5-10µm) remained below or around 2% with the MRI-Linac gradient strength. In patients measured with the conventional MRI, we found sub-regions reflecting either dominating restricted diffusion or dominating diffusional exchange in and around brain lesions compared to the noisy appearing white matter. On the conventional MRI system, the TDD contrast maps showed consistent tumor sub-regions indicating different dominating TDD effects, potentially providing information on the spatial tumor heterogeneity. On the MRI-Linac, the available TDD contrast measured in asparagus showed the same trends as with the conventional MRI but remained close to typical measurement noise levels when simulated in common cancer cell sizes. On conventional MRI systems with moderate gradient strengths, the TDD contrast could potentially be used as a tool to identify which time-dependent effects to include when choosing a biophysical model for more specific tumor characterization.

Intracellular diffusion in the cytoplasm increases with cell size in fission yeast.

Diffusion in the cytoplasm can greatly impact cellular processes, yet regulation of macromolecular diffusion remains poorly understood. There is increasing evidence that cell size affects the density and macromolecular composition of the cytoplasm. Here, we studied whether cell size affects diffusion at the scale of macromolecules tens of microns in diameter. We analyzed the diffusive motions of intracellular genetically-encoded multimeric 40 nm nanoparticles (cytGEMs) in the cytoplasm of the fission yeast Schizosaccharomyces pombe . Using cell size mutants, we showed that cytGEMs diffusion coefficients decreased in smaller cells and increased in larger cells. This increase in diffusion in large cells may be due to a decrease in the DNA-to-Cytoplasm ratio, as diffusion was not affected in large multinucleate cytokinesis mutants. In investigating the underlying causes of altered cytGEMs diffusion, we found that the proteomes of large and small cells exhibited size-specific changes, including the sub-scaling of ribosomal proteins in large cells. Comparison with a similar dataset from human cells revealed that features of size-dependent proteome remodeling were conserved. These studies demonstrate that cell size is an important parameter in determining the biophysical properties and the composition of the cytoplasm.

Waldenstrom's Macroglobulinemia: A Case Report

Waldenström's macroglobulinemia (WM) is a rare, slow-growing hematologic malignancy marked by elevated levels of monoclonal immunoglobulin M (IgM) and bone marrow infiltration by lymphoplasmacytic cells. This case details a 72-year-old man who, during a pre-anesthetic consultation for lumbar spinal stenosis surgery, presented with neurological symptoms, fatigue, and headaches. Examination revealed pallor, and laboratory tests indicated anemia and an elevated erythrocyte sedimentation rate. Serum protein electrophoresis identified a monoclonal IgM spike, and bone marrow aspiration showed significant infiltration by small lymphoid cells, lymphoplasmacytoid cells, and plasma cells. WM was confirmed, and the patient was treated with dexamethasone, rituximab, and cyclophosphamide, with positive follow-up progress. This case underscores the importance of considering WM in the differential diagnosis for patients with unexplained anemia and elevated IgM levels, highlighting the need for timely diagnosis and treatment to manage potential complications.

Zinc pyrithione ameliorates colitis in mice by interacting on intestinal epithelial TRPA1 and TRPV4 channels

AimsAlthough zinc pyrithione (ZPT) has been studied as topical antimicrobial and cosmetic consumer products, little is known about its pharmacological actions in gastrointestinal (GI) health and inflammation. Our aims were to investigate the effects of ZPT on transient receptor potential (TRP) channels and Ca2+ signaling in intestinal epithelial cells (IECs) and its therapeutic potential for colitis. Main methodsDigital Ca2+ imaging and patch-clamp electrophysiology were performed on human colonic epithelial cells (HCoEpiC) and rat small intestinal epithelial cells (IEC-6). The transcription levels of proinflammatory cytokines such as IL-1β were detected by RTq-PCR. Dextran sulfate sodium (DSS) was used to induce colitis in mice. Key findingsZPT dose-dependently induced Ca2+ signaling and membrane currents in IECs, which were attenuated by selective blockers of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 4 (TRPV4) channels, respectively. Interestingly, Ca2+ entry via TRPA1 channels inhibited the activity of TRPV4 channels in HCoEpiC, but not vice versa. ZPT significantly promoted migration of IECs by activating TRPA1 and TRPV4 channels. ZPT reversed lipopolysaccharides (LPS)-induced changes in mRNA expression of TRPA1 and TRPV4. Moreover, ZPT decreased mRNA levels of pro-inflammatory factors promoted by LPS in HCoEpiC, which were restored by selective TRPA1 blocker. In whole animal studies in vivo, ZPT significantly ameliorated DSS-induced body weight loss, colon shortening and increases in stool score, serum calprotectin and lactic acid (LD) in mouse model of colitis. SignificanceZPT exerts anti-colitic action likely by anti-inflammation and pro-mucosal healing through TRP channels in IECs. The present study not only expands pharmacology spectrum of ZPT in GI tract, but also repurposes it to a potential drug for colitis therapy.