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The Journal of Physical Chemistry. B Jun 2024Microscopic understanding of protein-RNA interactions is important for different biological activities, such as RNA transport, translation, splicing, silencing, etc....
Microscopic understanding of protein-RNA interactions is important for different biological activities, such as RNA transport, translation, splicing, silencing, etc. Polyadenine (Poly(A)) binding proteins (PABPs) make up a class of regulatory proteins that play critical roles in protecting the poly(A) tails of cellular mRNAs from nuclease degradation. In this work, we performed molecular dynamics simulations to investigate the conformational modifications of human PABP protein and poly(A) RNA that occur during complexation. It is demonstrated that the intermediate linker domain of the protein transforms from a disordered coil-like structure to a helical form during the recognition process, leading to the formation of the complex. On the other hand, disordered collapsed coil-like RNA on complexation has been found to transform into a rigid extended conformation. Importantly, the binding free energy calculation showed that the thermodynamic stability of the complex is primarily guided by favorable hydrophobic interactions between the protein and the RNA.
PubMed: 38941243
DOI: 10.1021/acs.jpcb.4c00704 -
The International Journal of Oral &... Jun 2024To investigate residual debris within internal features of new "as received" dental implants.
PURPOSE
To investigate residual debris within internal features of new "as received" dental implants.
MATERIALS AND METHODS
A total of 15 new dental implants representing various dental implant brands were obtained in sealed containers from the manufacturers. Batch numbers and implant types were documented. In a controlled setting, implants were carefully unpacked, and their internal aspects were visually examined. Further analysis involved light microscopy imaging to document and photograph any foreign material. The internal aspect of the implants were sampled with both an endodontic paper cone and a fine bristle brush swab. These were inserted into the implant, rotated three times, then removed and examined under a microscope at 30x magnification. Post sampling some of the brushes/swabs were washed with alcohol to remove debris that could be further examined under magnification.
RESULTS
Inspection of the implants without magnification revealed no visible foreign materials. However, under light microscopy (x10 and x30), all 15 implants exhibited small black particles at various internal sites, including connections, threads, and deep within screw channels. Swabs evaluated at magnification detected what appeared to be metal particles in all 15 implants, ranging from distinct metal shards to smaller particles.
CONCLUSION
This study suggests that implant manufacturers have not effectively removed all machining debris from within implant bodies, potentially producing prosthetic and clinical complications.
PubMed: 38941171
DOI: 10.11607/jomi.11002 -
Head and Neck Pathology Jun 2024Previous studies have shown that at least a of intraoral eosinophilic ulcer is best classified as a CD30 + T-cell lymphoproliferative disorder (LPD), with... (Review)
Review
BACKGROUND
Previous studies have shown that at least a of intraoral eosinophilic ulcer is best classified as a CD30 + T-cell lymphoproliferative disorder (LPD), with histopathology reminiscent of lymphomatoid papulosis (LyP) of the skin. Microscopically, a mixed population of inflammatory cells, often including eosinophils and varying numbers of atypical lymphoid cells, frequently expressing CD30, is typical for LyP, whose clinicopathological spectrum includes type A, B, C, D, E, and LyP with DUSP22/IRF4 rearrangement. To date, about 27 intraoral LyP cases have been reported. Of them, 7 cases were diagnosed as LyP type C, which is frequently confused with anaplastic large cell lymphoma (ALCL) on histopathology.
METHODS
A 60-year-old male was referred for a one-month history of a tongue ulcer.
RESULTS
Microscopy showed numerous subepithelial atypical large lymphoid cells, which expressed CD4 (with partial loss of CD3, CD5, and CD7), CD8 (few cells), CD30 (about 50%, in non-diffuse pattern with size variability), TIA-1, and Ki-67 (85%), without staining for CD56, ALK, LMP1, and EBER1/2, concerning for a diagnosis of ALCL. However, after three weeks, the lesion completely healed.
CONCLUSION
We present here a rare case of intraoral CD30+ T-cell LPD that we believe is the oral counterpart of cutaneous LyP type C.
Topics: Humans; Male; Lymphomatoid Papulosis; Middle Aged; Ki-1 Antigen; Diagnosis, Differential; Immunohistochemistry; Lymphoproliferative Disorders; Biomarkers, Tumor; T-Lymphocytes
PubMed: 38941041
DOI: 10.1007/s12105-024-01664-z -
Physical Chemistry Chemical Physics :... Jun 2024In this work, the ferroelectric and semiconducting properties of the organic semiconducting ferroelectric benzotrithiophene tricarboxamide (BTTTA), and especially their...
In this work, the ferroelectric and semiconducting properties of the organic semiconducting ferroelectric benzotrithiophene tricarboxamide (BTTTA), and especially their nonlinear coupling, are theoretically investigated. BTTTA is an exponent of a small class of semiconducting organic ferroelectrics for which experiments have established a surprising polarization direction dependence of the bulk conductivity at finite fields. First, molecular dynamics (MD) simulations are used to investigate the occurrence and, under the influence of an external electric field, the inversion of the macroscopic electric dipole that forms along the axis of supramolecular columns of BTTTA. The MD results are consistent with the experimentally observed ferroelectric behavior of the material. Building on the MD results, a QM/MM scheme is used to investigate the charge carrier mobility in the quasi-1D BTTTA stacks in the linear and non-linear regimes. Indeed, at finite electric fields, a clear resistance switching effect was observed in the form of a hole mobility that is a factor ∼2 larger for antiparallel orientations of the polarization and field than for a parallel orientation. This phenomenon can be understood as a microscopic ratchet that is based on the non-equilibrium interaction between the (oriented) dipoles and the (direction of the) charge transport.
PubMed: 38940915
DOI: 10.1039/d4cp01632g -
Head and Neck Pathology Jun 2024Patient derived organoids (PDOs) are 3D in vitro models and have shown to better reflect patient and tumor heterogeneity than conventional 2D cell lines. To utilize PDOs...
INTRODUCTION
Patient derived organoids (PDOs) are 3D in vitro models and have shown to better reflect patient and tumor heterogeneity than conventional 2D cell lines. To utilize PDOs in clinical settings and trials for biomarker discovery or drug response evaluation, it is valuable to determine the best way to optimize sample selection for maximum PDO establishment. In this study, we assess patient, tumor and tissue sampling factors and correlate them with successful PDO establishment in a well-documented cohort of patients with head and neck squamous cell carcinoma (HNSCC).
METHODS
Tumor and non-tumorous adjacent tissue samples were obtained from HNSCC patients during routine biopsy or resection procedures at the University Medical Center Utrecht. The tissue was subsequently processed to establish PDOs. The sample purity was determined as the presence of epithelial cells in the culture on the day of organoid isolation as visualized microscopically by the researcher. PDO establishment was recorded for all samples. Clinical data was obtained from the medical records and was correlated to PDO establishment and presence of epithelial cells.
RESULTS
Organoids could be established in 133/250 (53.2%) primary tumor site tissues. HNSCC organoid establishment tended to be more successful if patients were younger than the median age of 68 years (74/123 (60.2%) vs. 59/127 (46.5%), p = 0.03). For a subset of samples, the presence of epithelial cells in the organoid culture on the day of organoid isolation was recorded in 112/149 (75.2%) of these samples. When cultures were selected for presence of epithelial cells, organoid establishment increased to 76.8% (86/112 samples).
CONCLUSION
This study found a trend between age and successful organoid outgrowth in patients with HNSCC younger than 68 years and emphasizes the value of efficient sampling regarding PDO establishment.
Topics: Humans; Organoids; Squamous Cell Carcinoma of Head and Neck; Aged; Female; Middle Aged; Male; Head and Neck Neoplasms; Adult; Aged, 80 and over
PubMed: 38940869
DOI: 10.1007/s12105-024-01658-x -
Alternative Therapies in Health and... Jun 2024Cerebral aneurysm can rupture a blood vessel and cause bleeding in the brain. Microsurgical clipping of the tumor neck has been reported to be effective in treating...
Clinical Efficacy of Early Microsurgical Clipping of Tumor Neck in the Treatment of Cerebral Aneurysm Rupture and Bleeding and Its Impact on Oxidative Stress Response and Prognosis of Patients.
BACKGROUND
Cerebral aneurysm can rupture a blood vessel and cause bleeding in the brain. Microsurgical clipping of the tumor neck has been reported to be effective in treating cerebral aneurysm rupture and bleeding.
OBJECTIVE
This research attempted to clarify the clinical efficacy of early microsurgical clipping of tumor neck for treating cerebral aneurysm rupture and bleeding, and its impact on prognosis of patients.
DESIGN
This was a retrospective study.
SETTING
This study was carried out in the Department of Neurosurgery, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital.
UNLABELLED
One hundred patients with cerebral aneurysm rupture and bleeding patients aged from 23 to 70 years old, and diagnosed with CA rupture and bleeding through imaging examinations such as CT angiography (CTA) and digital subtraction angiography (DSA), and there was spontaneous subarachnoid hemorrhage treated in our hospital from November 2020 to November 2022 were selected and divided into an experimental group (n=25) and a control group (n=25) according to surgical time.
INTERVENTIONS
All patients underwent microsurgical clipping of the tumor neck for therapy. Under microscope monitoring, the temporal and frontal lobes of the patient were separated, and the tumor body was selected in the internal carotid artery and cerebral artery. After the tumor neck of the patient was exposed, the artery supplying blood was clipped and appropriate tumor clips were selected. The control group chose to undergo surgery 72 h after the onset of cerebral aneurysm rupture and bleeding, while the experimental group chose to undergo complete surgery within 72 h after the onset of cerebral aneurysm rupture and bleeding. After surgery, targeted treatment were given to patients in 2 groups based on their physical condition, such as dehydration to reduce intracranial pressure, anti-vasospasm, anti-infection, monitoring of neurological changes, and monitoring of vital signs. Cerebral angiography should also be performed for reexamination.
PRIMARY OUTCOME MEASURES
(1) incidence of complications (2) cognitive function scores assessed by Montreal Cognitive Assessment (MoCA) (3) prognosis assessed by Glasgow Outcome Scale (GOS) (4) surgical indicators (5) oxidative stress response and (6) quality of life assessed by short form 36 health survey questionnaire (SF-36).
RESULTS
Compared to the control group, the incidence of complications in the experimental group exhibited depletion (24.0% vs 8.0%) (P < .05), the prognosis in the experimental group exhibited elevation [(2.23±0.45) points vs (4.12±0.3) points] (P < .05), the hospitalization time in the experimental group exhibited depletion [(15.69±1.21) d vs (11.31±0.65) d] (P < .05), the nomination, abstraction, language, orientation, attention, delayed recall and visual and executive function scores and total scores in experimental group exhibited elevation [(2.69±0.52 points, 2.07±0.63 points, 3.02±0.44 points, 2.45±0.51 points, 3.12±0.36 points, 2.14±0.75 points, 3.15±0.64 points and 17.24±2.15 points) vs (4.25±0.65 points, 3.88±1.08 points, 5.03±0.73 points, 3.34±0.72 points, 4.05±0.66 points, 3.85±0.33 points, 5.02±1.04 points and 26.89±1.33 points)] (P < .05), serum levels of oxidative stress-related indicators in the experimental group exhibited depletion [(462.14±48.47 ng/mL, 281.14±36.44 ng/mL and 1.62±0.12 nmol/mL) vs (365.58±44.56 ng/mL, 201.51±34.47 ng/mL and 1.15±0.1 nmol/mL)](P < .05) and the quality of life in experimental group exhibited elevation [(73.65±7.43 points, 72.24±7.23 points, 73.25±7.36 points, 70.24±7.05 points and 72.16±7.25 points) vs (81.25±8.14 points, 80.87±8.09 points, 81.43±8.15 points, 80.57±8.07 points and 81.32±8.14 points)] (P < .05).
CONCLUSION
Early microsurgical clipping of the tumor neck can downregulate risk of complications and cognitive impairment of cerebral aneurysm rupture and bleeding patients, which is worthy for clinical application.
PubMed: 38940784
DOI: No ID Found -
Sarcoidosis, Vasculitis, and Diffuse... Jun 2024Although pulmonary manifestations occur frequently in ANCA-associated vasculitis (AAV), empirical evidence of their impact on pulmonary function is scarce. This study...
BACKGROUND AND AIM
Although pulmonary manifestations occur frequently in ANCA-associated vasculitis (AAV), empirical evidence of their impact on pulmonary function is scarce. This study analyzed pulmonary function test (PFT) data from a large cohort of patients with AVV. Results were correlated with findings from diagnostic imaging and disease activity.
METHODS
Data from AAV patients with PFTs performed between 2008 and 2018 were extracted retrospectively from the database of a tertiary vasculitis center. Demographic and disease characteristics, imaging data and follow-up results were assessed and compared to PFT results.
RESULTS
The final analysis encompassed 147 patients. The mean time between first PFT and follow-up was 7.0 ± 11.0 months. In Granulomatosis with Polyangiitis (GPA), forced expiratory vital capacity (FVCex, p<0.001), residual volume (RV, p<0.001) and the diffusion capacity of carbon oxide (TLCO, p=0.003) were significantly reduced compared to the reference value of 100% predicted. There was no significant difference between patients with or without pulmonary manifestations. In Microscopic Polyangiitis (MPA), reductions of FVCex (p<0.001), TLC (p=0.005), and TLCO (p=0.003) were observed. In Eosinophilic Granulomatosis with Polyangiitis (EGPA), total airway resistance (RAWtot, p=0.024) and RV (p=0.009) were significantly elevated and TLCO was reduced (p=0.014). Interstitial lung disease (ILD) is associated with a decline of FVCex (-15.7%, p=0.0028), TLC (-26.5%, p<0.001), RV (-38.9%, p=0.023) and TLCO (-29.1%, p=0.007). Significant differences were neither detected between first PFT and follow-up examination, nor between patients with active versus inactive disease.
CONCLUSIONS
AAV patients presented with characteristic alterations in PFTs according to their respective pulmonary and/or airway manifestations. These results did not change over time and were independent from vasculitis activity.
PubMed: 38940708
DOI: 10.36141/svdld.v41i2.15577 -
Analytical Chemistry Jun 2024Several reductases, including nitroreductase, are upregulated under hypoxic conditions characterized by an oxygen-deficient microenvironment. Given that hypoxia is a...
Several reductases, including nitroreductase, are upregulated under hypoxic conditions characterized by an oxygen-deficient microenvironment. Given that hypoxia is a prominent feature of solid tumors, our investigation focused on developing a bioconjugative probe designed for staining tissue under hypoxic conditions, particularly activated by nitroreductase. This probe, developed using our trigger-release-bioconjugation system rooted in the -quinone methide chemistry, exhibited selective activation by nitroreductase and fluorophore labeling within mitochondria and endoplasmic reticulum. As a result, it displayed sustained fluorescence that persisted even after washing steps in cells and tissues. We applied this innovative probe to stain mouse kidney tissue in an acute kidney injury model induced by inadequate oxygen supply. Among various organ tissues examined, only kidney tissue showed significantly higher fluorescence in the injury model compared with the control tissue, as revealed by two-photon microscopic imaging. This research presents a promising avenue for the development of practical staining agents for image-guided tumor surgery.
PubMed: 38940602
DOI: 10.1021/acs.analchem.4c01274 -
The Journal of Chemical Physics Jun 2024The surfaces of many minerals are covered by naturally occurring cations that become partially hydrated and can be replaced by hydronium or other cations when the...
The surfaces of many minerals are covered by naturally occurring cations that become partially hydrated and can be replaced by hydronium or other cations when the surface is exposed to water or an aqueous solution. These ion exchange processes are relevant to various chemical and transport phenomena, yet elucidating their microscopic details is challenging for both experiments and simulations. In this work, we make a first step in this direction by investigating the behavior of the native K+ ions at the interface between neat water and the muscovite mica (001) surface with ab-initio-based machine learning molecular dynamics and enhanced sampling simulations. Our results show that the desorption of the surface K+ ions in pure ion-free water has a significant free energy barrier irrespective of their local surface arrangement. In contrast, facile K+ diffusion between mica's ditrigonal cavities characterized by different Al/Si orderings is observed. This behavior suggests that the K+ ions may favor a dynamic disordered surface arrangement rather than complete desorption when exposed to deionized water.
PubMed: 38940541
DOI: 10.1063/5.0217720 -
Nucleus (Austin, Tex.) Dec 2024The analysis of nucleocytoplasmic transport of proteins and messenger RNA has been the focus of advanced microscopic approaches. Recently, it has been possible to... (Review)
Review
The analysis of nucleocytoplasmic transport of proteins and messenger RNA has been the focus of advanced microscopic approaches. Recently, it has been possible to identify and visualize individual pre-ribosomal particles on their way through the nuclear pore complex using both electron and light microscopy. In this review, we focused on the transport of pre-ribosomal particles in the nucleus on their way to and through the pores.
Topics: Cell Nucleolus; Nuclear Pore; Cytoplasm; Active Transport, Cell Nucleus; Humans; Animals; Ribosomes; Cell Nucleus
PubMed: 38940456
DOI: 10.1080/19491034.2024.2373052