bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond the microcirculation: sequestration of infected red blood cells and reduced flow in large draining veins in experimental cerebral malaria
Authors: Oelschlegel A. M. , Bhattacharjee R. , Wenk P. , Harit K. , Rothkötter H-J , Koch S. P. , Boehm-Sturm P. , Matuschewski K. , Budinger E. , Schlüter D. , Goldschmidt J. , Nishanth G.
Published: March 2024

Sequestration of infected red blood cells (iRBCs) in the microcirculation is a hallmark of cerebral malaria (CM) in post-mortem human brains. It remains controversial how this might be linked to the different disease manifestations, in particular brain swelling leading to brain herniation and death. The main hypotheses focus on iRBC-triggered inflammation and mechanical obstruction of blood flow. Here, we test these hypotheses using murine models of experimental CM (ECM), SPECT-imaging of radiolabeled iRBCs and cerebral perfusion, MR-angiography, q-PCR, and immunohistochemistry. We show that iRBC accumulation and reduced flow precede inflammation. Unexpectedly, we find that iRBCs accumulate not only in the microcirculation but also in large draining veins and sinuses, particularly at the rostral confluence. We identify two parallel venous streams from the superior sagittal sinus that open into the rostral rhinal veins and are partially connected to infected skull bone marrow. The flow in these vessels is reduced early, and the spatial patterns of pathology correspond to venous drainage territories. Our data suggest that venous efflux reductions downstream of the microcirculation are causally linked to ECM pathology, and that the different spatiotemporal patterns of edema development in mice and humans could be related to anatomical differences in venous anatomy.
Biomimetic nanocluster photoreceptors for adaptative circular polarization vision
Authors: Wen Wei , Liu Guocai , Wei Xiaofang , Huang Haojie , Wang Chong , Zhu Danlei , Sun Jianzhe , Yan Huijuan , Huang Xin , Shi Wenkang , Dai Xiaojuan , Dong Jichen , Jiang Lang , Guo Yunlong , Wang Hanlin , Liu Yunqi
Published: March 2024

Nanoclusters with atomically precise structures and discrete energy levels are considered as nanoscale semiconductors for artificial intelligence. However, nanocluster electronic engineering and optoelectronic behavior have remained obscure and unexplored. Hence, we create nanocluster photoreceptors inspired by mantis shrimp visual systems to satisfy the needs of compact but multi-task vision hardware and explore the photo-induced electronic transport. Wafer-scale arrayed photoreceptors are constructed by a nanocluster-conjugated molecule heterostructure. Nanoclusters perform as an in-sensor charge reservoir to tune the conductance levels of artificial photoreceptors by a light valve mechanism. A ligand-assisted charge transfer process takes place at nanocluster interface and it features an integration of spectral-dependent visual adaptation and circular polarization recognition. This approach is further employed for developing concisely structured, multi-task, and compact artificial visual systems and provides valuable guidelines for nanocluster neuromorphic devices.
Integrative cross-omics and cross-context analysis elucidates molecular links underlying genetic effects on complex traits
Authors: Lu Yihao , Oliva Meritxell , Pierce Brandon L. , Liu Jin , Chen Lin S.
Published: March 2024

Genetic effects on functionally related ‘omic’ traits often co-occur in relevant cellular contexts, such as tissues. Motivated by the multi-tissue methylation quantitative trait loci (mQTLs) and expression QTLs (eQTLs) analysis, we propose X-ING (Cross-INtegrative Genomics) for cross-omics and cross-context integrative analysis. X-ING takes as input multiple matrices of association statistics, each obtained from different omics data types across multiple cellular contexts. It models the latent binary association status of each statistic, captures the major association patterns among omics data types and contexts, and outputs the posterior mean and probability for each input statistic. X-ING enables the integration of effects from different omics data with varying effect distributions. In the multi-tissue cis-association analysis, X-ING shows improved detection and replication of mQTLs by integrating eQTL maps. In the trans-association analysis, X-ING reveals an enrichment of trans-associations in many disease/trait-relevant tissues.
The spliceosome-associated protein CWC15 promotes miRNA biogenesis in Arabidopsis
Authors: Zhou Bangjun , Yu Huihui , Xue Yong , Li Mu , Zhang Chi , Yu Bin
Published: March 2024

MicroRNAs (miRNAs) play a key role in regulating gene expression and their biogenesis is precisely controlled through modulating the activity of microprocessor. Here, we report that CWC15, a spliceosome-associated protein, acts as a positive regulator of miRNA biogenesis. CWC15 binds the promoters of genes encoding miRNAs (MIRs), promotes their activity, and increases the occupancy of DNA-dependent RNA polymerases at MIR promoters, suggesting that CWC15 positively regulates the transcription of primary miRNA transcripts (pri-miRNAs). In addition, CWC15 interacts with Serrate (SE) and HYL1, two key components of microprocessor, and is required for efficient pri-miRNA processing and the HYL1-pri-miRNA interaction. Moreover, CWC15 interacts with the 20 S proteasome and PRP4KA, facilitating SE phosphorylation by PRP4KA, and subsequent non-functional SE degradation by the 20 S proteasome. These data reveal that CWC15 ensures optimal miRNA biogenesis by maintaining proper SE levels and by modulating pri-miRNA levels. Taken together, this study uncovers the role of a conserved splicing-related protein in miRNA biogenesis.
Universal growth of perovskite thin monocrystals from high solute flux for sensitive self-driven X-ray detection
Authors: Liu Da , Zheng Yichu , Sui Xin Yuan , Wu Xue Feng , Zou Can , Peng Yu , Liu Xinyi , Lin Miaoyu , Wei Zhanpeng , Zhou Hang , Yao Ye-Feng , Dai Sheng , Yuan Haiyang , Yang Hua Gui , Yang Shuang , Hou Yu
Published: March 2024

Metal-halide perovskite thin monocrystals featuring efficient carrier collection and transport capabilities are well suited for radiation detectors, yet their growth in a generic, well-controlled manner remains challenging. Here, we reveal that mass transfer is one major limiting factor during solution growth of perovskite thin monocrystals. A general approach is developed to overcome synthetic limitation by using a high solute flux system, in which mass diffusion coefficient is improved from 1.7×10–10 to 5.4×10–10 m2 s–1 by suppressing monomer aggregation. The generality of this approach is validated by the synthesis of 29 types of perovskite thin monocrystals at 40–90 °C with the growth velocity up to 27.2 μm min–1. The as-grown perovskite monocrystals deliver a high X-ray sensitivity of 1.74×105 µC Gy−1 cm−2 without applied bias. The findings regarding limited mass transfer and high-flux crystallization are crucial towards advancing the preparation and application of perovskite thin monocrystals.
Structural basis for autoinhibition by the dephosphorylated regulatory domain of Ycf1
Authors: Khandelwal Nitesh Kumar , Tomasiak Thomas M.
Published: March 2024

Yeast Cadmium Factor 1 (Ycf1) sequesters glutathione and glutathione-heavy metal conjugates into yeast vacuoles as a cellular detoxification mechanism. Ycf1 belongs to the C subfamily of ATP Binding Cassette (ABC) transporters characterized by long flexible linkers, notably the regulatory domain (R-domain). R-domain phosphorylation is necessary for activity, whereas dephosphorylation induces autoinhibition through an undefined mechanism. Because of its transient and dynamic nature, no structure of the dephosphorylated Ycf1 exists, limiting understanding of this R-domain regulation. Here, we capture the dephosphorylated Ycf1 using cryo-EM and show that the unphosphorylated R-domain indeed forms an ordered structure with an unexpected hairpin topology bound within the Ycf1 substrate cavity. This architecture and binding mode resemble that of a viral peptide inhibitor of an ABC transporter and the secreted bacterial WXG peptide toxins. We further reveal the subset of phosphorylation sites within the hairpin turn that drive the reorganization of the R-domain conformation, suggesting a mechanism for Ycf1 activation by phosphorylation-dependent release of R-domain mediated autoinhibition.
Light and matter co-confined multi-photon lithography
Authors: Guan Lingling , Cao Chun , Liu Xi , Liu Qiulan , Qiu Yiwei , Wang Xiaobing , Yang Zhenyao , Lai Huiying , Sun Qiuyuan , Ding Chenliang , Zhu Dazhao , Kuang Cuifang , Liu Xu
Published: March 2024

Mask-free multi-photon lithography enables the fabrication of arbitrary nanostructures low cost and more accessible than conventional lithography. A major challenge for multi-photon lithography is to achieve ultra-high precision and desirable lateral resolution due to the inevitable optical diffraction barrier and proximity effect. Here, we show a strategy, light and matter co-confined multi-photon lithography, to overcome the issues via combining photo-inhibition and chemical quenchers. We deeply explore the quenching mechanism and photoinhibition mechanism for light and matter co-confined multiphoton lithography. Besides, mathematical modeling helps us better understand that the synergy of quencher and photo-inhibition can gain a narrowest distribution of free radicals. By using light and matter co-confined multiphoton lithography, we gain a 30 nm critical dimension and 100 nm lateral resolution, which further decrease the gap with conventional lithography.
Structure of full-length ERGIC-53 in complex with MCFD2 for cargo transport
Authors: Watanabe Satoshi , Kise Yoshiaki , Yonezawa Kento , Inoue Mariko , Shimizu Nobutaka , Nureki Osamu , Inaba Kenji
Published: March 2024

ERGIC-53 transports certain subsets of newly synthesized secretory proteins and membrane proteins from the endoplasmic reticulum to the Golgi apparatus. Despite numerous structural and functional studies since its identification, the overall architecture and mechanism of action of ERGIC-53 remain unclear. Here we present cryo-EM structures of full-length ERGIC-53 in complex with its functional partner MCFD2. These structures reveal that ERGIC-53 exists as a homotetramer, not a homohexamer as previously suggested, and comprises a four-leaf clover-like head and a long stalk composed of three sets of four-helix coiled-coil followed by a transmembrane domain. 3D variability analysis visualizes the flexible motion of the long stalk and local plasticity of the head region. Notably, MCFD2 is shown to possess a Zn2+-binding site in its N-terminal lid, which appears to modulate cargo binding. Altogether, distinct mechanisms of cargo capture and release by ERGIC- 53 via the stalk bending and metal binding are proposed.
Poincaré sphere trajectory encoding metasurfaces based on generalized Malus’ law
Authors: Deng Zi-Lan , Hu Meng-Xia , Qiu Shanfeng , Wu Xianfeng , Overvig Adam , Li Xiangping , Alù Andrea
Published: March 2024

As a fundamental property of light, polarization serves as an excellent information encoding carrier, playing significant roles in many optical applications, including liquid crystal displays, polarization imaging, optical computation and encryption. However, conventional polarization information encoding schemes based on Malus’ law usually consider 1D polarization projections on a linear basis, implying that their encoding flexibility is largely limited. Here, we propose a Poincaré sphere (PS) trajectory encoding approach with metasurfaces that leverages a generalized form of Malus’ law governing universal 2D projections between arbitrary elliptical polarization pairs spanning the entire PS. Arbitrary polarization encodings are realized by engineering PS trajectories governed by either arbitrary analytic functions or aligned modulation grids of interest, leading to versatile polarization image transformation functionalities, including histogram stretching, thresholding and image encryption within non-orthogonal PS loci. Our work significantly expands the encoding dimensionality of polarization information, unveiling new opportunities for metasurfaces in polarization optics for both quantum and classical regimes.
Data-driven prediction of colonization outcomes for complex microbial communities
Authors: Wu Lu , Wang Xu-Wen , Tao Zining , Wang Tong , Zuo Wenlong , Zeng Yu , Liu Yang-Yu , Dai Lei
Published: March 2024

Microbial interactions can lead to different colonization outcomes of exogenous species, be they pathogenic or beneficial in nature. Predicting the colonization of exogenous species in complex communities remains a fundamental challenge in microbial ecology, mainly due to our limited knowledge of the diverse mechanisms governing microbial dynamics. Here, we propose a data-driven approach independent of any dynamics model to predict colonization outcomes of exogenous species from the baseline compositions of microbial communities. We systematically validate this approach using synthetic data, finding that machine learning models can predict not only the binary colonization outcome but also the post-invasion steady-state abundance of the invading species. Then we conduct colonization experiments for commensal gut bacteria speciesEnterococcus faeciumandAkkermansia muciniphilain hundreds of human stool-derived in vitro microbial communities, confirming that the data-driven approaches can predict the colonization outcomes in experiments. Furthermore, we find that while most resident species are predicted to have a weak negative impact on the colonization of exogenous species, strongly interacting species could significantly alter the colonization outcomes, e.g.,Enterococcus faecalisinhibits the invasion ofE. faeciuminvasion. The presented results suggest that the data-driven approaches are powerful tools to inform the ecology and management of microbial communities.
Architecture of symbiotic dinoflagellate photosystem I–light-harvesting supercomplex in Symbiodinium
Authors: Zhao Long-Sheng , Wang Ning , Li Kang , Li Chun-Yang , Guo Jian-Ping , He Fei-Yu , Liu Gui-Ming , Chen Xiu-Lan , Gao Jun , Liu Lu-Ning , Zhang Yu-Zhong
Published: March 2024

Symbiodinium are the photosynthetic endosymbionts for corals and play a vital role in supplying their coral hosts with photosynthetic products, forming the nutritional foundation for high-yield coral reef ecosystems. Here, we determine the cryo-electron microscopy structure of Symbiodinium photosystem I (PSI) supercomplex with a PSI core composed of 13 subunits including 2 previously unidentified subunits, PsaT and PsaU, as well as 13 peridinin-Chl a/c-binding light-harvesting antenna proteins (AcpPCIs). The PSI–AcpPCI supercomplex exhibits distinctive structural features compared to their red lineage counterparts, including extended termini of PsaD/E/I/J/L/M/R and AcpPCI-1/3/5/7/8/11 subunits, conformational changes in the surface loops of PsaA and PsaB subunits, facilitating the association between the PSI core and peripheral antennae. Structural analysis and computational calculation of excitation energy transfer rates unravel specific pigment networks in Symbiodinium PSI–AcpPCI for efficient excitation energy transfer. Overall, this study provides a structural basis for deciphering the mechanisms governing light harvesting and energy transfer in Symbiodinium PSI–AcpPCI supercomplexes adapted to their symbiotic ecosystem, as well as insights into the evolutionary diversity of PSI–LHCI among various photosynthetic organisms.
Improving the degradation and magnetization performance of FePC amorphous alloys by annealing treatment
Authors: Qi Z. G. , Chen Q. , Wang Z. X. , Song Z. Q. , Kim K. B. , Pang J. , Zhang X. H. , Wang W. M.
Published: March 2024

The Fe80PxC20-x ingots and amorphous ribbons (4.5 ≤ x ≤ 6.5) are arc melted and melt spun respectively. The Rhodamine B degradation performance of as spun and annealed ribbons are investigated with various methods. In present alloys, increasing P content (cP) can inhibit the precipitation of primary α-Fe and graphite phases, and promote the formation of eutectic α-Fe + Fe3C + Fe3P phases in ingots and annealed ribbons. With increasing annealing temperature (Tan), the primary α-Fe grain size of the ribbons with cP = 4.5 at.% increases gradually and that of the ribbons with cP = 6.5 at.% increases firstly and then decreases. The degradation performance and reusability of the ribbons show a similar Tan-dependent behavior, which can be explained by the size effect of the galvanic cells. Meanwhile, the saturation magnetisation Bs and coercivity Hc of the ribbons with cP = 4.5 and 6.5 at.% increase with increasing Tan, showing a near-linear change of the reaction rate constant k against ln (Bs·Hc). This work not only studies the mechanism of improving degradation performance for FePC amorphous alloys by annealing treatment, but also reveals a correlation between degradation performance and magnetization performance of FePC alloys.
Advanced brain aging in Parkinson’s disease with cognitive impairment
Authors: Chen Chang-Le , Cheng Shao-Ying , Montaser-Kouhsari Leila , Wu Wen-Chao , Hsu Yung-Chin , Tai Chun-Hwei , Tseng Wen-Yih Isaac , Kuo Ming-Che , Wu Ruey-Meei
Published: March 2024

Patients with Parkinson’s disease and cognitive impairment (PD-CI) deteriorate faster than those without cognitive impairment (PD-NCI), suggesting an underlying difference in the neurodegeneration process. We aimed to verify brain age differences in PD-CI and PD-NCI and their clinical significance. A total of 94 participants (PD-CI, n = 27; PD-NCI, n = 34; controls, n = 33) were recruited. Predicted age difference (PAD) based on gray matter (GM) and white matter (WM) features were estimated to represent the degree of brain aging. Patients with PD-CI showed greater GM-PAD (7.08 ± 6.64 years) and WM-PAD (8.82 ± 7.69 years) than those with PD-NCI (GM: 1.97 ± 7.13, Padjusted = 0.011; WM: 4.87 ± 7.88, Padjusted = 0.049) and controls (GM: -0.58 ± 7.04, Padjusted = 0.004; WM: 0.88 ± 7.45, Padjusted = 0.002) after adjusting demographic factors. In patients with PD, GM-PAD was negatively correlated with MMSE (Padjusted = 0.011) and MoCA (Padjusted = 0.013) and positively correlated with UPDRS Part II (Padjusted = 0.036). WM-PAD was negatively correlated with logical memory of immediate and delayed recalls (Padjusted = 0.003 and Padjusted < 0.001). Also, altered brain regions in PD-CI were identified and significantly correlated with brain age measures, implicating the neuroanatomical underpinning of neurodegeneration in PD-CI. Moreover, the brain age metrics can improve the classification between PD-CI and PD-NCI. The findings suggest that patients with PD-CI had advanced brain aging that was associated with poor cognitive functions. The identified neuroimaging features and brain age measures can serve as potential biomarkers of PD-CI.
Mapping of secondary forest age in China using stacked generalization and Landsat time series
Authors: Zhang Shaoyu , Xu Hanzeyu , Liu Aixia , Qi Shuhua , Hu Bisong , Huang Min , Luo Jin
Published: March 2024

A national distribution of secondary forest age (SFA) is essential for understanding the forest ecosystem and carbon stock in China. While past studies have mainly used various change detection algorithms to detect forest disturbance, which cannot adequately characterize the entire forest landscape. This study developed a data-driven approach for improving performances of the Vegetation Change Tracker (VCT) and Continuous Change Detection and Classification (CCDC) algorithms for detecting the establishment of forest stands. An ensemble method for mapping national-scale SFA by determining the establishment time of secondary forest stands using change detection algorithms and dense Landsat time series was proposed. A dataset of national secondary forest age for China (SFAC) for 1 to 34 and with a 30-m spatial resolution was produced from the optimal ensemble model. This dataset provides national, continuous spatial SFA information and can improve understanding of secondary forests and the estimation of forest carbon storage in China.
The safety and efficacy of clevidipine for blood pressure management in neurocritical patients: a systematic review and meta-analysis
Authors: Widiastuti Monika , Bisri Dewi Yulianti , Rachman Iwan Abdul
Published: March 2024

We aim to determine the safety and efficacy of clevidipine for neurocritical patients. To comprehensively identify relevant studies, a systematic search strategy was employed using the following keywords: “clevidipine”, “high blood pressure”, “hypertension”, “Neuroscience Intensive Care”, “neuro critical”, and “neurosurgical patients”. Searches were conducted in the Clinicaltrials.gov, PubMed, and EuroPMC databases, with the search extending until September 1, 2023. The primary outcomes of interest were the time needed to achieve the target systolic blood pressure (SBP) and the percentage of time a patient remained within the targeted SBP range. Secondary outcomes included SBP values, duration of intensive care unit (ICU) stay in days, rates of hypotension, and rates of tachycardia. We included five retrospective cohort studies (n = 443), utilizing nicardipine as the primary comparator. Comparison of the time to reach target systolic blood pressure (SBP) revealed no significant difference between medications (SMD = − 1.09, p = 0.33). Likewise, the achieved SBP target showed no notable distinction (RR = 1.15, p = 0.81). However, clevidipine exhibited a slightly higher percentage of time within the target SBP range (SMD = 0.33, p = 0.04), albeit with moderate heterogeneity. Importantly, all included studies were retrospective cohort studies, underscoring the methodological context of the investigation. Clevidipine and the control group were found to be comparable in terms of achieving target SBP. Clevidipine may have a slight advantage in maintaining blood pressure within the desired range, but further research is needed to confirm this finding.
Mechanical behavior of hot extruded aluminum 6082 chip
Authors: Mahmoud Seif El Din , El-Gamasy Ramadan , El-Wahab Ayman A. Abd
Published: March 2024

In a bid to address the energy-intensive nature of primary aluminum production, this study explores the solid-state recycling of aluminum alloy 6082 chips through direct hot extrusion. Compacted at room temperature, chips were extruded at temperatures (350, 425, and 500 °C) and reduction ratios (6, 8.5, and 11) to optimize mechanical properties. Extensive analyses, including ANOVA and linear regressions, of strength, density, and microstructure revealed significant influences of those extrusion parameters. Optimizing these parameters within the study's aforementioned working ranges can impact the recycled material's strength; with a 36% reduction ratio increase and 20% temperature increase modestly reducing ultimate strength (2%), while a 20% temperature increase alone lowers yield strength more noticeably (9%). These findings highlight the potential for enhanced recycling and sustainable manufacturing.
Application of 32 factorial design for loratadine-loaded nanosponge in topical gel formulation: comprehensive in-vitro and ex vivo evaluations
Authors: Sivadasan Durgaramani , Venkatesan Krishnaraju , Mohamed Jamal Moideen Muthu , Alqahtani Saud , Asiri Yahya I. , Faisal Mennatullah M. , Ibrahim Adel Ehab , Alrashdi Yahya Bin Abdullah , Menaa Farid , Deeb Sami El
Published: March 2024

Loratadine (LoR) is a highly lipophilic and practically insoluble in water, hence having a low oral bioavailability. As it is formulated as topical gel, it competitively binds with the receptors, thus reducing the side-effects. The objective of this study was to prepare LoR loaded nanosponge (LoR-NS) in gel for topical delivery. Nine different formulations of emulsion were prepared by solvent evaporation method with polyvinyl alcohol (PVA), ethyl cellulose (EC), and dichloromethane (DCM). Based on 32 Full Factorial Design (FFD), optimization was carried out by varying the concentration of LOR:EC ratio and stirring rate. The preparations were subjected for the evaluation of particle size (PS), in vitro release, zeta potential (ZP) and entrapment efficiency (EE). The results revealed that the NS dispersion was nanosized with sustained release profiles and significant PS. The optimised formulation was formulated and incorporated into carbopol 934P hydrogel. The formulation was then examined to surface morphological characterizations using scanning electron microscopy (SEM) which depicted spherical NS. Stability studies, undertaken for 2 months at 40 ± 2 °C/75 ± 5% RH, concluded to the stability of the formulation. The formulation did not cause skin irritation. Therefore, the prepared NS hydrogel proved to be a promising applicant for LoR as a novel drug delivery system (NDDS) for safe, sustained and controlled topical application.
Animal-borne soundscape logger as a system for edge classification of sound sources and data transmission for monitoring near-real-time underwater soundscape
Authors: Noda Takuji , Koizumi Takuya , Yukitake Naoto , Yamamoto Daisuke , Nakaizumi Tetsuro , Tanaka Kotaro , Okuyama Junichi , Ichikawa Kotaro , Hara Takeshi
Published: March 2024

The underwater environment is filled with various sounds, with its soundscape composed of biological, geographical, and anthropological sounds. Our work focused on developing a novel method to observe and classify these sounds, enriching our understanding of the underwater ecosystem. We constructed a biologging system allowing near-real-time observation of underwater soundscapes. Utilizing deep-learning-based edge processing, this system classifies the sources of sounds, and upon the tagged animal surfacing, it transmits positional data, results of sound source classification, and sensor readings such as depth and temperature. To test the system, we attached the logger to sea turtles (Chelonia mydas) and collected data through a cellular network. The data provided information on the location-specific sounds detected by the sea turtles, suggesting the possibility to infer the distribution of specific species of organisms over time. The data showed that not only biological sounds but also geographical and anthropological sounds can be classified, highlighting the potential for conducting multi-point and long-term observations to monitor the distribution patterns of various sound sources. This system, which can be considered an autonomous mobile platform for oceanographic observations, including soundscapes, has significant potential to enhance our understanding of acoustic diversity.
A novel role for phospholamban in the thalamic reticular nucleus
Authors: Klocke Benjamin , Britzolaki Aikaterini , Saurine Joseph , Ott Hayden , Krone Kylie , Bahamonde Kiara , Thelen Connor , Tzimas Christos , Sanoudou Despina , Kranias Evangelia G. , Pitychoutis Pothitos M.
Published: March 2024

The thalamic reticular nucleus (TRN) is a brain region that influences vital neurobehavioral processes, including executive functioning and the generation of sleep rhythms. TRN dysfunction underlies hyperactivity, attention deficits, and sleep disturbances observed across various neurodevelopmental disorders. A specialized sarco-endoplasmic reticulum calcium (Ca2+) ATPase 2 (SERCA2)-dependent Ca2+ signaling network operates in the dendrites of TRN neurons to regulate their bursting activity. Phospholamban (PLN) is a prominent regulator of SERCA2 with an established role in myocardial Ca2+-cycling. Our findings suggest that the role of PLN extends beyond the cardiovascular system to impact brain function. Specifically, we found PLN to be expressed in TRN neurons of the adult mouse brain, and utilized global constitutive and innovative conditional genetic knockout mouse models in concert with electroencephalography (EEG)-based somnography and the 5-choice serial reaction time task (5-CSRTT) to investigate the role of PLN in sleep and executive functioning, two complex behaviors that map onto thalamic reticular circuits. The results of the present study indicate that perturbed PLN function in the TRN results in aberrant TRN-dependent phenotypes in mice (i.e., hyperactivity, impulsivity and sleep deficits) and support a novel role for PLN as a critical regulator of SERCA2 in the TRN neurocircuitry.
Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma
Authors: Nejo Takahide , Wang Lin , Leung Kevin K. , Wang Albert , Lakshmanachetty Senthilnath , Gallus Marco , Kwok Darwin W. , Hong Chibo , Chen Lee H. , Carrera Diego A. , Zhang Michael Y. , Stevers Nicholas O. , Maldonado Gabriella C. , Yamamichi Akane , Watchmaker Payal B. , Naik Akul , Shai Anny , Phillips Joanna J. , Chang Susan M. , Wiita Arun P. , Wells James A. , Costello Joseph F. , Diaz Aaron A. , Okada Hideho
Published: March 2024

Despite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.
Tumor-infiltrating immune cells and survival in head and neck squamous cell carcinoma: a retrospective computational study
Authors: Zhang Lei , Wang Wei-Quan , Chen Jun-Hong , Feng Jia , Liao Ya-Zhou , Zou You , Liu Rong
Published: March 2024

The immune infiltration profiles of the tumor microenvironment have effects on the prognosis of head and neck squamous cell carcinoma (HNSCC). Whereas, HNSCC is a heterogeneous group of tumors, but past work has not taken this into consideration. Herein, we investigate the associations between survival and the function of immune cells in different tumorigenic sites of HNSCC. 1149 samples of HNSCC were collected from publicly accessible databases. Based on gene expression data, CIBERSORTx was applied to determine the proportion of 22 immune cell subpopulations. In the Cox regression model, the associations between overall survival, disease-free survival, and immune cells were examined, modeling gene expression and immune cell proportion as quartiles. Consensus cluster analysis was utilized to uncover immune infiltration profiles. Regardless of tumor sites, CD8+ T cells and activated CD4 memory T cells were associated with favorable survival, while eosinophils were the opposite. The survival of the hypopharynx, oral cavity, and larynx subsites was somewhat affected by immune cells, while the survival of the oropharynx subsite potentially was the most impacted. High expression of TIGIT, CIITA, and CXCR6 was linked to better survival, mainly in the oropharynx subsite. Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy.
Novel electrochemical platform based on C3N4-graphene composite for the detection of neuron-specific enolase as a biomarker for lung cancer
Authors: Junping Zhang , Zheng Wei , ZhengFang Tang , Yue L. I. Ji , PengHang An , Mingli Zhang , Hongzhi An
Published: March 2024

Lung cancer remains the leading cause of cancer mortality worldwide. Small cell lung cancer (SCLC) accounts for 10–15% of cases and has an overall 5-years survival rate of only 15%. Neuron-specific enolase (NSE) has been identified as a useful biomarker for early SCLC diagnosis and therapeutic monitoring. This work reports an electrochemical immunosensing platform based on a graphene-graphitic carbon nitride (g-C3N4) nanocomposite for ultrasensitive NSE detection. The g-C3N4 nanosheets and graphene nanosheets were synthesized via liquid exfoliation and integrated through self-assembly to form the nanocomposite. This nanocomposite was used to modify screen-printed carbon electrodes followed by covalent immobilization of anti-NSE antibodies. The unique properties of the graphene-g-C3N4 composite facilitated efficient antibody loading while also enhancing electron transfer efficiency and electrochemical response. Systematic optimization of experimental parameters was performed. The immunosensor exhibited a wide linear detection range of 10 pg/mL to 100 ng/mL and low limit of detection of 3 pg/mL for NSE along with excellent selectivity against interferences. Real serum matrix analysis validated the applicability of the developed platform for sensitive and accurate NSE quantifica-tion at clinically relevant levels. This novel graphene-g-C3N4 nanocomposite based electro-chemical immunoassay demonstrates great promise for early diagnosis of SCLC.
Mathematical formulation and computation of the dynamics of blood flow, heat and mass transfer during MRI scanning
Authors: Mwapinga Annord
Published: March 2024

Computational modeling of arterial blood flow, heat and mass transfer during MRI scanning is studied. The flow is assumed to be unsteady, in-compressible, and asymmetric. Mathematical formulation considers the presence of stenosis, joule heating viscous dissipation and chemical reaction. The explicit finite difference scheme is used to numerically solve the model equations. The MATLAB software was used to plot the graphical results. The study reveals that, during MRI scanning, both radial and axial velocities diminish with increase in the strength of magnetic fields. Besides, the study found that, Eckert number and Hartman number enhance the blood’s temperature and the same, diminishes with increase in Prandtl and Reynolds numbers. Concentration profile is observed to decline with increase in chemical reaction parameter, Schmidt number and Reynolds number. Soret number on the other hand, is observed to positively influence the concentration.
Lesion-conditioning of synthetic MRI-derived subtraction-MIPs of the breast using a latent diffusion model
Authors: Kapsner Lorenz A. , Folle Lukas , Hadler Dominique , Eberle Jessica , Balbach Eva L. , Liebert Andrzej , Ganslandt Thomas , Wenkel Evelyn , Ohlmeyer Sabine , Uder Michael , Bickelhaupt Sebastian
Published: March 2024

The purpose of this feasibility study is to investigate if latent diffusion models (LDMs) are capable to generate contrast enhanced (CE) MRI-derived subtraction maximum intensity projections (MIPs) of the breast, which are conditioned by lesions. We trained an LDM with n = 2832 CE-MIPs of breast MRI examinations of n = 1966 patients (median age: 50 years) acquired between the years 2015 and 2020. The LDM was subsequently conditioned with n = 756 segmented lesions from n = 407 examinations, indicating their location and BI-RADS scores. By applying the LDM, synthetic images were generated from the segmentations of an independent validation dataset. Lesions, anatomical correctness, and realistic impression of synthetic and real MIP images were further assessed in a multi-rater study with five independent raters, each evaluating n = 204 MIPs (50% real/50% synthetic images). The detection of synthetic MIPs by the raters was akin to random guessing with an AUC of 0.58. Interrater reliability of the lesion assessment was high both for real (Kendall’s W = 0.77) and synthetic images (W = 0.85). A higher AUC was observed for the detection of suspicious lesions (BI-RADS $$\ge $$
≥
4) in synthetic MIPs (0.88 vs. 0.77; p = 0.051). Our results show that LDMs can generate lesion-conditioned MRI-derived CE subtraction MIPs of the breast, however, they also indicate that the LDM tended to generate rather typical or ‘textbook representations’ of lesions.
The impact of rainfall on the sea surface salinity: a mesocosm study
Authors: Gassen Lisa , Esters Leonie , Ribas-Ribas Mariana , Wurl Oliver
Published: March 2024

Sea surface salinity may serve as a tracer for freshwater fluxes because it is linked to evaporation and precipitation that force the freshwater balance of the ocean’s surface. The relationship between freshwater fluxes and salinity anomalies in the upper few centimeters remains widely unknown. In a mechanistic approach, we investigated how these anomalies develop by conducting experiments with artificial rain over a large basin. We measured conductivity and temperature at different depths and rain characteristics (intensity, rain temperature, droplet sizes, and velocities). In the absence of turbulence, the rain causes a strong salinity change of up to 6.02 g kg$$^{-1}$$

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in 0–4 cm depth. At the highest rain intensity of 56 mm h$$^{-1}$$

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, salinity changed thrice as fast as at an intensity of 18 mm h$$^{-1}$$

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. At the sea surface microlayer (first millimeter of the surface) the anomalies are always highest and reached a maximum of 14.18 g kg$$^{-1}$$

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. With mechanical mixing, salinity changes were less pronounced (maximum SML salinity anomaly: 6.17 g kg$$^{-1}$$

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), and freshwater was mixed fast with the existing seawater body. In general, our study shows that freshwater remains in the upper few centimeters, and even with induced turbulence, are not mixed below 16 cm.
Pulpotomy for teeth with irreversible pulpitis in immature permanent teeth: a retrospective case series study
Authors: Zhang Na , Kang Qian , Cheng Yuzhao
Published: March 2024

To evaluate the success of pulpotomy in treating immature permanent teeth with irreversible pulpitis. This case series included patients with irreversible pulpitis admitted to the Department of Oral Medicine at the author’s Hospital between 2015 and 2020. The pulpotomies were carried out by clinicians with > 5 years of working experience. The follow-up findings and radiographic images were reviewed by two attending dentists. This study included 49 teeth from 48 children (25 boys and 23 girls). The follow-up was 23.3 ± 6.8 months (from 12 to 40 months). The success rate of pulpotomy was 85.7% (42/49). Pulpotomy failed in seven teeth (14.3%). The treatment success rate for traumatic crown fracture was lower than for dental caries and dens evaginatus (P < 0.001). There were no significant differences in the success rate of the pulp-capping agent, tooth root developmental phase, and pulpotomy method (all P > 0.05). Pulpotomy might be successfully used to treat immature permanent teeth with irreversible pulpitis in young patients mainly caused by caries and a fractured tubercle of dens evaginatus.
Anti-oral cancer properties of potential probiotic lactobacilli isolated from traditional milk, cheese, and yogurt
Authors: Nami Yousef , Tavallaei Omid , Kiani Amir , Moazami Nesa , Samari Mahya , Derakhshankhah Hossein , Jaymand Mehdi , Haghshenas Babak
Published: March 2024

This study investigates the probiotic and anti-cancer effects of 21 isolated Lactobacillus strains from cheese, milk, and yogurt in Kermanshah, Iran, on oral cancer cell lines KB and OSCC. Four selected isolates (Y33, M45, C5, and C28) displayed good viability and resistance to specific antibiotics. Notably, strains C28 and Y33 exhibited the best results, showing susceptibility or semi-susceptibility to five antibiotics. Y33, with high cell surface hydrophobicity (62%), demonstrated significant anti-pathogenic activity, inhibiting the growth of tested pathogens and displaying strong adhesion to human intestinal Caco-2 cells (52%). Further assessments, including acridine orange/ethidium bromide staining and mRNA expression analysis, revealed four isolates (C5, C28, M45, and Y33) with promising probiotic properties. Particularly, Y33’s protein-based extract metabolites showed dose- and time-dependent inhibition of KB and OSCC cancer cell lines, inducing apoptosis without significant cytotoxic effects on normal cells. Y33 (Lactiplantibacillus plantarum) exhibited the strongest probiotic potential, surpassing conventional anti-cancer drugs, suggesting its therapeutic potential for preventing oral cancer cell proliferation and improving survival rates in oral cancer patients.
Protein kinase C activity modulates nuclear Lamin A/C dynamics in HeLa cells
Authors: Wesley Chase C. , North Dallin V. , Levy Daniel L.
Published: March 2024

The nuclear lamina serves important functions in the nucleus, providing structural support to the nuclear envelope and contributing to chromatin organization. The primary proteins that constitute the lamina are nuclear lamins whose functions are impacted by post-translational modifications, including phosphorylation by protein kinase C (PKC). While PKC-mediated lamin phosphorylation is important for nuclear envelope breakdown during mitosis, less is known about interphase roles for PKC in regulating nuclear structure. Here we show that overexpression of PKC ß, but not PKC α, increases the Lamin A/C mobile fraction in the nuclear envelope in HeLa cells without changing the overall structure of Lamin A/C and Lamin B1 within the nuclear lamina. Conversely, knockdown of PKC ß, but not PKC α, reduces the Lamin A/C mobile fraction. Thus, we demonstrate an isoform-specific role for PKC in regulating interphase Lamin A/C dynamics outside of mitosis.
A large cross sectional study on diaper utilization and beneficial role in outdoor activity and emotions among incontinence elderly people
Authors: Zhang Yunwei , Fang Dawei , Luo Yashuang , Wang Changying , Wan Lingshan , Cao Yifan , Xin Hongyun , Ding Hansheng
Published: March 2024

This study was designed based on a cross-sectional investigation conducted Shanghai, China. Demographic characteristics, diaper utilization, Activities of Daily Living (ADL) and emotion were collected by Unified Needs Assessment Form for Elderly Care Questionnaire. Cognition function was assessed by Mini-mental State Examination (MMSE) scale. Multivariate logistic regression was used for statistical analysis. The diaper utilization rate was 31.2%. Female, higher level of education, poorer ADL and cognition, more severe incontinence and financial dependence on others were facilitating factors for diaper usage (P < 0.05). The possibility of using diaper differed according to the intimacy of caregivers. Among incontinent individuals with relatively good ADL and cognition level, diaper utilization can significantly decrease the risk of going out only once a month (OR: 2.63 vs 4.05), and going out less than once a month (OR: 5.32 vs 6.53). Incontinence people who going out at least once a week had a lower risk of some negative emotion. Significantly, diaper utilization further decreased this risk. In conclusion, for incontinence elderly people with relatively independent ability, proper use of diaper may improve the frequency of outdoor activity and emotion. Nevertheless, diaper utilization should be decided based on elderly people’s own will.
Mitochondrial variants of complex I genes associated with leprosy clinical subtypes
Authors: de Souza Felipe Gouvea , Silva Caio S. , de Araújo Gilderlanio S. , Santana-da-Silva Mayara N. , Gobbo Angélica Rita , da Silva Moisés Batista , Pinto Pablo , da Costa Patrícia Fagundes , Salgado Claudio Guedes , Ribeiro-dos-Santos Ândrea , Cavalcante Giovanna C.
Published: March 2024

Leprosy is a chronic bacterial infection mainly caused by Mycobacterium leprae that primarily affects skin and peripheral nerves. Due to its ability to absorb carbon from the host cell, the bacillus became dependent on energy production, mainly through oxidative phosphorylation. In fact, variations in genes of Complex I of oxidative phosphorylation encoded by mtDNA have been associated with several diseases in humans, including bacterial infections, which are possible influencers in the host response to leprosy. Here, we investigated the presence of variants in the mtDNA genes encoding Complex I regarding leprosy, as well as the analysis of their pathogenicity in the studied cohort. We found an association of 74 mitochondrial variants with either of the polar forms, Pole T (Borderline Tuberculoid) or Pole L (Borderline Lepromatous and Lepromatous) of leprosy. Notably, six variants were exclusively found in both clinical poles of leprosy, including m.4158A>G and m.4248T>C in MT-ND1, m.13650C>A, m.13674T>C, m.12705C>T and m.13263A>G in MT-ND5, of which there are no previous reports in the global literature. Our observations reveal a substantial number of mutations among different groups of leprosy, highlighting a diverse range of consequences associated with mutations in genes across these groups. Furthermore, we suggest that the six specific variants exclusively identified in the case group could potentially play a crucial role in leprosy susceptibility and its clinical differentiation. These variants are believed to contribute to the instability and dysregulation of oxidative phosphorylation during the infection, further emphasizing their significance.