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Advanced Science (Weinheim,... Jun 2024Collaboration between cancer treatment and inflammation management has emerged as an integral facet of comprehensive cancer care. Nevertheless, the development of...
Collaboration between cancer treatment and inflammation management has emerged as an integral facet of comprehensive cancer care. Nevertheless, the development of interventions concurrently targeting both inflammation and cancer has encountered significant challenges stemming from various external factors. Herein, a bioactive agent synthesized by genetically engineering melanin-producing Bacillus thuringiensis (B. thuringiensis) bacteria, simultaneously achieves eco-friendly photothermal agent and efficient reactive oxygen/nitrogen species (RONS) scavenger benefits, perfectly tackling present toughies from inflammation to cancer therapies. The biologically derived melanin exhibits exceptional photothermal-conversion performance, facilitating potent photonic hyperthermia that effectively eradicates tumor cells and tissues, thereby impeding tumor growth. Additionally, the RONS-scavenging properties of melanin produced by B. thuringiensis bacteria contribute to inflammation reduction, augmenting the efficacy of photothermal tumor repression. This study presents a representative paradigm of genetic engineering in B. thuringiensis bacteria to produce functional agents tailored for diverse biomedical applications, encompassing inflammation and cancer therapy.
PubMed: 38943265
DOI: 10.1002/advs.202308506 -
Cytometry. Part a : the Journal of the... Jun 2024Autofluorescence lifetime imaging microscopy (FLIM) is sensitive to metabolic changes in single cells based on changes in the protein-binding activities of the metabolic...
Autofluorescence lifetime imaging microscopy (FLIM) is sensitive to metabolic changes in single cells based on changes in the protein-binding activities of the metabolic co-enzymes NAD(P)H. However, FLIM typically relies on time-correlated single-photon counting (TCSPC) detection electronics on laser-scanning microscopes, which are expensive, low-throughput, and require substantial post-processing time for cell segmentation and analysis. Here, we present a fluorescence lifetime-sensitive flow cytometer that offers the same TCSPC temporal resolution in a flow geometry, with low-cost single-photon excitation sources, a throughput of tens of cells per second, and real-time single-cell analysis. The system uses a 375 nm picosecond-pulsed diode laser operating at 50 MHz, alkali photomultiplier tubes, an FPGA-based time tagger, and can provide real-time phasor-based classification (i.e., gating) of flowing cells. A CMOS camera produces simultaneous brightfield images using far-red illumination. A second PMT provides two-color analysis. Cells are injected into the microfluidic channel using a syringe pump at 2-5 mm/s with nearly 5 ms integration time per cell, resulting in a light dose of 2.65 J/cm that is well below damage thresholds (25 J/cm at 375 nm). Our results show that cells remain viable after measurement, and the system is sensitive to autofluorescence lifetime changes in Jurkat T cells with metabolic perturbation (sodium cyanide), quiescent versus activated (CD3/CD28/CD2) primary human T cells, and quiescent versus activated primary adult mouse neural stem cells, consistent with prior studies using multiphoton FLIM. This TCSPC-based autofluorescence lifetime flow cytometer provides a valuable label-free method for real-time analysis of single-cell function and metabolism with higher throughput than laser-scanning microscopy systems.
PubMed: 38943226
DOI: 10.1002/cyto.a.24883 -
Malaria Journal Jun 2024Microscopic detection of malaria parasites is labour-intensive, time-consuming, and expertise-demanding. Moreover, the slide interpretation is highly dependent on the...
BACKGROUND
Microscopic detection of malaria parasites is labour-intensive, time-consuming, and expertise-demanding. Moreover, the slide interpretation is highly dependent on the staining technique and the technician's expertise. Therefore, there is a growing interest in next-generation, fully- or semi-integrated microscopes that can improve slide preparation and examination. This study aimed to evaluate the clinical performance of miLab™ (Noul Inc., Republic of Korea), a fully-integrated automated microscopy device for the detection of malaria parasites in symptomatic patients at point-of-care in Sudan.
METHODS
This was a prospective, case-control diagnostic accuracy study conducted in primary health care facilities in rural Khartoum, Sudan in 2020. According to the outcomes of routine on-site microscopy testing, 100 malaria-positive and 90 malaria-negative patients who presented at the health facility and were 5 years of age or older were enrolled consecutively. All consenting patients underwent miLab™ testing and received a negative or suspected result. For the primary analysis, the suspected results were regarded as positive (automated mode). For the secondary analysis, the operator reviewed the suspected results and categorized them as either negative or positive (corrected mode). Nested polymerase chain reaction (PCR) was used as the reference standard, and expert light microscopy as the comparator.
RESULTS
Out of the 190 patients, malaria diagnosis was confirmed by PCR in 112 and excluded in 78. The sensitivity of miLab™ was 91.1% (95% confidence interval [CI] 84.2-95.6%) and the specificity was 66.7% (95% Cl 55.1-67.7%) in the automated mode. The specificity increased to 96.2% (95% Cl 89.6-99.2%), with operator intervention in the corrected mode. Concordance of miLab with expert microscopy was substantial (kappa 0.65 [95% CI 0.54-0.76]) in the automated mode, but almost perfect (kappa 0.97 [95% CI 0.95-0.99]) in the corrected mode. A mean difference of 0.359 was found in the Bland-Altman analysis of the agreement between expert microscopy and miLab™ for quantifying parasite counts.
CONCLUSION
When used in a clinical context, miLab™ demonstrated high sensitivity but low specificity. Expert intervention was shown to be required to improve the device's specificity in its current version. miLab™ in the corrected mode performed similar to expert microscopy. Before clinical application, more refinement is needed to ensure full workflow automation and eliminate human intervention. Trial registration ClinicalTrials.gov: NCT04558515.
Topics: Sudan; Microscopy; Humans; Case-Control Studies; Prospective Studies; Point-of-Care Systems; Female; Male; Sensitivity and Specificity; Child; Child, Preschool; Adult; Adolescent; Malaria; Young Adult; Middle Aged
PubMed: 38943203
DOI: 10.1186/s12936-024-05029-3 -
Scientific Reports Jun 2024Adam's Bridge is a submerged ridge connecting India and Sri Lanka, generally regarded as a chain of shoals extending for ~ 29 km from Dhanushkodi on the Indian side...
Adam's Bridge is a submerged ridge connecting India and Sri Lanka, generally regarded as a chain of shoals extending for ~ 29 km from Dhanushkodi on the Indian side to Talaimannar Island of Sri Lanka. A high-resolution digital bathymetric elevation model generated using the seafloor returned photons of ICESat-2 was used to understand the intricate details of Adam's Bridge structure. Photons emanating from ICESat-2's green laser have the potential to detect the seafloor up to a depth of ~ 40 m; taking a cue from this potentiality, in our research, we have accrued ~ 0.2 million photons representing the depth information and generated a 10 m resolution bathymetric data for the extent of Adam's Bridge. Visual interpretations made from this bathymetric data through 3D perspectives with multi-directional lighting effects, and also with the derived parameters like contours, slope, and volumetric analysis, enabled us to recognize the current form of Adam's Bridge's physical features. The results from our research confirm that, in its entirety, Adam's Bridge is a submarine continuation of Dhanushkodi and Talaimannar Island. Throughout the crest line of Adam's Bridge, approximately 1.5 km on either side is highly undulating within the super-shallow water with occurrences of sudden depths. There is an asymmetry of transverse slopes to the base on both sides of Adam's Bridge, indicating dominant transgression of material energy from the waters of the Gulf of Mannar compared to the Palk Strait. The volume of Adam's Bridge computed in our research yielded a value of ~ 1 km; interestingly, only 0.02 percent of this volume is above the mean sea level, and in general, the same is visible in optical satellite imagery-in total ~ 99.98 percent of the Adam's Bridge is submerged in shallow and super-shallow waters.
PubMed: 38942892
DOI: 10.1038/s41598-024-65908-2 -
Nature Communications Jun 2024The tunable properties of halide perovskite/two dimensional (2D) semiconductor mixed-dimensional van der Waals heterostructures offer high flexibility for innovating...
The tunable properties of halide perovskite/two dimensional (2D) semiconductor mixed-dimensional van der Waals heterostructures offer high flexibility for innovating optoelectronic and photonic devices. However, the general and robust growth of high-quality monocrystalline halide perovskite/2D semiconductor heterostructures with attractive optical properties has remained challenging. Here, we demonstrate a universal van der Waals heteroepitaxy strategy to synthesize a library of facet-specific single-crystalline halide perovskite/2D semiconductor (multi)heterostructures. The obtained heterostructures can be broadly tailored by selecting the coupling layer of interest, and can include perovskites varying from all-inorganic to organic-inorganic hybrid counterparts, individual transition metal dichalcogenides or 2D heterojunctions. The CsPbIBr/WSe heterostructures demonstrate ultrahigh optical gain coefficient, reduced gain threshold and prolonged gain lifetime, which are attributed to the reduced energetic disorder. Accordingly, the self-organized halide perovskite/2D semiconductor heterostructure lasers show highly reproducible single-mode lasing with largely reduced lasing threshold and improved stability. Our findings provide a high-quality and versatile material platform for probing unique optoelectronic and photonic physics and developing further electrically driven on-chip lasers, nanophotonic devices and electronic-photonic integrated systems.
PubMed: 38942769
DOI: 10.1038/s41467-024-49364-0 -
The Journal of Neuroscience : the... Jun 2024During navigation, the neocortex must actively integrate learned spatial context with current sensory experience to guide behaviours. However, the relative encoding of...
During navigation, the neocortex must actively integrate learned spatial context with current sensory experience to guide behaviours. However, the relative encoding of spatial and sensorimotor information among cortical cells, and whether hippocampal feedback continues to modify these properties in familiar environments, remains poorly understood. Thus, two-photon microscopy of male and female Thy1-GCaMP6s mice was used to longitudinally image neurons spanning superficial retrosplenial cortex and layers II-Va of primary and secondary motor cortices before and after bilateral dorsal hippocampal lesions. During behaviour on a familiar cued treadmill, the locations of two added obstacles were interchanged to decouple place-tuning from cue-tuning among the position correlated cells with fields at those locations. The subpopulations of place- and cue-tuned cells each formed interareal gradients such that higher-level cortical regions exhibited higher fractions of place cells, whereas lower-level regions exhibited higher fractions of cue cells. Position correlated cells in motor cortex also formed translaminar gradients; cells closer to the cortical surface were more likely to exhibit fields and were more sparsely and precisely tuned than deeper cells. After dorsal hippocampal lesions, a neural representation of the learned environment persisted but retrosplenial cortex exhibited significantly increased cue-tuning and, in motor cortices, both position correlated cell recruitment and population activity at the unstable obstacle locations became more homogeneously elevated across laminae. Altogether, these results support that the hippocampus continues to modulate cortical responses in familiar environments, and the relative impact of top-down feedback obeys hierarchical interareal and interlaminar gradients opposite to the flow of bottom-up sensory inputs. During learning, the hippocampus imparts spatial context to memory representations throughout the superficial neocortex. However, the post-learning role of the hippocampus has not been well defined. The results of this study suggest that, during navigation of a familiar environment, the hippocampus continues to link unreliable sensory attributes to a stable contextual framework, effectively updating the learned model of the environment. The results are also consistent with top-down suppression of sensory-evoked activity during behaviour, which varied in strength according to hierarchical proximity to the hippocampus. This effect was abolished by bilateral lesions of the dorsal hippocampus, supporting that the hippocampus plays an ongoing role in propagating context-dependent predictions throughout the cortical hierarchy, a core hypothesis of the predictive coding theoretical framework.
PubMed: 38942472
DOI: 10.1523/JNEUROSCI.1619-23.2024 -
Korean Journal of Radiology Jul 2024Since the emergence of the first photon-counting computed tomography (PCCT) system in late 2021, its advantages and a wide range of applications in all fields of... (Review)
Review
Since the emergence of the first photon-counting computed tomography (PCCT) system in late 2021, its advantages and a wide range of applications in all fields of radiology have been demonstrated. Compared to standard energy-integrating detector-CT, PCCT allows for superior geometric dose efficiency in every examination. While this aspect by itself is groundbreaking, the advantages do not stop there. PCCT facilitates an unprecedented combination of ultra-high-resolution imaging without dose penalty or field-of-view restrictions, detector-based elimination of electronic noise, and ubiquitous multi-energy spectral information. Considering the high demands of orthopedic imaging for the visualization of minuscule details while simultaneously covering large portions of skeletal and soft tissue anatomy, no subspecialty may benefit more from this novel detector technology than musculoskeletal radiology. Deeply rooted in experimental and clinical research, this review article aims to provide an introduction to the cosmos of PCCT, explain its technical basics, and highlight the most promising applications for patient care, while also mentioning current limitations that need to be overcome.
Topics: Humans; Tomography, X-Ray Computed; Photons; Musculoskeletal Diseases; Musculoskeletal System; Radiation Dosage
PubMed: 38942460
DOI: 10.3348/kjr.2024.0096 -
Physics in Medicine and Biology Jun 2024Conventional image quality metrics assume independence between images which is not preserved within spectral CT datasets, limiting their utility for characterizing...
Conventional image quality metrics assume independence between images which is not preserved within spectral CT datasets, limiting their utility for characterizing energy selective images. In this work, we developed a metrology to characterize energy selective images by incorporating the shared information between images within a spectral CT dataset. Approach: Signal-to-noise ratio was extended into a multivariate space where each image was treated as a separate information channel. The general definition was applied to contrast to define a multivariate contrast-to-noise ratio (CNR). The matrix contained two types of terms: a conventional CNR term, characterizing image quality within each image, and covariance weighted CNR (Covar-CNR), characterizing contrast relative to covariance between images. The metrology was demonstrated using experimental data from an investigational photon-counting CT scanner. A cylindrical water phantom containing vials of iodine and gadolinium (2, 4, 8 mg/mL) was imaged with variable tube current, tube voltage, and energy threshold. Two image series (threshold and bin images) containing two images each were defined based upon the contribution of photons to reconstructed images. Analysis of variance was calculated between CNR terms and image acquisition variables. A multivariate regression was fit to experimental data. Main Results: Bin images had a slightly higher mean and wider standard deviation (Covar-CNRlo: 3.38 ±17.25, Covar-CNRhi: 5.77±30.64) than threshold images (Covar-CNRlo: 2.08 ±1.89, Covar-CNRhi: 3.45±2.49) across all conditions. Analysis of variance found each acquisition variable had a significant relationship with both Covar-CNR terms. The multivariate regression model suggested that material concentration had the largest impact on all CNR terms. Significance: In this work, we described a theoretical framework to extend the signal-to-noise ratio to a multivariate form to characterize images independently and provide insight regarding the relationship between images. Experimental data was used to demonstrate the insight that this metrology provides about image formation factors in spectral CT. .
PubMed: 38942009
DOI: 10.1088/1361-6560/ad5d4a -
Physics in Medicine and Biology Jun 2024Proton therapy is a limited resource and is typically not available to metastatic cancer patients. Combined proton-photon therapy (CPPT), where most fractions are...
Proton therapy is a limited resource and is typically not available to metastatic cancer patients. Combined proton-photon therapy (CPPT), where most fractions are delivered with photons and only few with protons, represents an approach to distribute proton resources over a larger patient population. In this study, we consider stereotactic radiotherapy of multiple brain or liver metastases, and develop an approach to optimally take advantage of a single proton fraction by optimizing the proton and photon dose contributions to each individual metastasis. CPPT treatments must balance two competing goals: 1) deliver a larger dose in the proton fractions to reduce integral dose, and 2) fractionate the dose in the normal tissue between metastases, which requires using the photon fractions. Such CPPT treatments are generated by simultaneously optimizing IMPT and IMRT plans based on their cumulative biologically effective dose (BED). The dose contributions of the proton and photon fractions to each individual metastasis are handled as additional optimization variables in the optimization problem. The method is demonstrated for two patients with 29 and 30 brain metastases, and two patients with 4 and 3 liver metastases. Optimized CPPT plans increase the proton dose contribution to most of the metastases, while using photons to fractionate the dose around metastases which are large or located close to critical structures. On average, the optimized CPPT plans reduce the mean brain BEDby 29% and the mean liver BEDby 42% compared to IMRT-only plans. Thereby, the CPPT plans approach the dosimetric quality of IMPT-only plans, for which the mean brain BEDand mean liver BEDare reduced by 28% and 58%, respectively, compared to IMRT-only plans. CPPT with optimized proton and photon dose contributions to individual metastases may benefit selected metastatic cancer patients without tying up major proton resources. .
PubMed: 38942008
DOI: 10.1088/1361-6560/ad5d48 -
Journal of Physics. Condensed Matter :... Jun 2024The application of half-metallic materials in single-molecule optoelectronic devices opens a promising way in advancing device performance and functionality, thus...
The application of half-metallic materials in single-molecule optoelectronic devices opens a promising way in advancing device performance and functionality, thus addressing a research question of significance. Here we propose a series of single-molecule devices with half-metallic FeN4-doped armchair graphene nanoribbon as electrodes and metalloporphyrin (MPr) molecules as photoresponsive materials for photon harvesting, which are driven by photogalvanic effects (PGEs). Through the quantum transport simulations, we systematically investigated the spin-polarized photocurrents under the linearly polarized light illumination in these devices. Since the exclusive opening only exists in the spin-up channel of the half-metallic nanoribbons, these devices can generate a large photocurrent in the spin-up direction whereas suppressing the spin-down photocurrent. Consequently, they exhibit an effective spin-filtering effect at numerous photon energies. Our study unveils the excellent spin-filtering effect achieved in single-molecule optoelectronic devices with half-metallic electrodes, showing instructive significance for the future design of new optoelectronic devices. .
PubMed: 38941993
DOI: 10.1088/1361-648X/ad5d37