A ZTF-7/RPS-2 complex mediates the cold-warm response in C. elegans.

Temperature greatly affects numerous biological processes in all organisms. How multicellular organisms respond to and are impacted by hypothermic stress remains elusive. Here, we found that cold-warm stimuli induced depletion of the RNA exosome complex in the nucleoli but enriched it in the nucleoplasm. To further understand the function and mechanism of cold-warm stimuli, we conducted forward genetic screening and identified ZTF-7, which is required for RNA exosome depletion from nucleoli upon transient cold-warm exposure in C. elegans. ZTF-7 is a putative ortholog of human ZNF277 that may contribute to language impairments. Immunoprecipitation followed by mass spectrometry (IP-MS) found that ZTF-7 interacted with RPS-2, which is a ribosomal protein of the small subunit and participates in pre-rRNA processing. A partial depletion of RPS-2 and other proteins of the small ribosomal subunit blocked the cold-warm stimuli-induced reduction of exosome subunits from the nucleoli. These results established a novel mechanism by which C. elegans responds to environmental cold-warm exposure.

Antisense ribosomal siRNAs inhibit RNA polymerase I-directed transcription in C. elegans.

Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that function in the nucleus. We previously found that erroneous rRNAs induce the generation of antisense ribosomal siRNAs (risiRNAs) which silence the expression of rRNAs via the nuclear RNAi defective (Nrde) pathway. To further understand the biological roles and mechanisms of this class of small regulatory RNAs, we conducted forward genetic screening to identify factors involved in risiRNA generation in Caenorhabditis elegans. We found that risiRNAs accumulated in the RNA exosome mutants. risiRNAs directed the association of NRDE proteins with pre-rRNAs and the silencing of pre-rRNAs. In the presence of risiRNAs, NRDE-2 accumulated in the nucleolus and colocalized with RNA polymerase I. risiRNAs inhibited the transcription elongation of RNA polymerase I by decreasing RNAP I occupancy downstream of the RNAi-targeted site. Meanwhile, exosomes mislocalized from the nucleolus to nucleoplasm in suppressor of siRNA (susi) mutants, in which erroneous rRNAs accumulated. These results established a novel model of rRNA surveillance by combining ribonuclease-mediated RNA degradation with small RNA-directed nucleolar RNAi system.

High spatial resolution of topographic imaging and Raman mapping by differential correlation-confocal Raman microscopy.

Confocal Raman microscopy (CRM) has found applications in many fields as a consequence of being able to measure molecular fingerprints and characterize samples without the need to employ labelling methods. However, limited spatial resolution has limited its application when identification of sub-micron features in materials is important. Here, we propose a differential correlation-confocal Raman microscopy (DCCRM) method to address this. This new method is based on the correlation product method of Raman scattering intensities acquired when the confocal Raman pinhole is placed at different (defocused) positions either side of the focal plane of the Raman collection lens. By using this correlation product, a significant enhancement in the spatial resolution of Raman mapping can be obtained. Compared with conventional CRM, these are 23.1% and 33.1% in the lateral and axial directions, respectively. We illustrate these improvements using in situ topographic imaging and Raman mapping of graphene, carbon nanotube, and silicon carbide samples. This work can potentially contribute to a better understanding of complex nanostructures in non-real time spectroscopic imaging fields.

Polysialic-Acid-Based Micelles Promote Neural Regeneration in Spinal Cord Injury Therapy.

Spinal cord injury (SCI) routinely causes the immediate loss and disruption of neurons followed by complicated secondary injuries, including inflammation, oxidative stress, and dense glial scar formation. Inhibitory factors in the lesion scar and poor intrinsic neural regeneration capacity restrict functional recovery after injury. Minocycline, which has neuroprotective activity, can alleviate secondary injury, but the long-term administration of this drug may cause toxicity. Polysialic acid (PSA) is a large cell-surface carbohydrate that is critical for central nervous system development and is capable of promoting precursor cell migration, axon path finding, and synaptic remodeling; thus, PSA plays a vital role in tissue repair and regeneration. Here, we developed a PSA-based minocycline-loaded nanodrug delivery system (PSM) for the synergistic therapy of spinal cord injury. The prepared PSM exerted marked anti-inflammatory and neuroprotective activities both in vitro and in vivo. The administration of PSM could significantly protect neurons and myelin sheaths from damage, reduce the formation of glial scar, recruit endogenous neural stem cells to the lesion site, and promote the regeneration of neurons and the extension of long axons throughout the glial scar, thereby largely improving the locomotor function of SCI rats and exerting a superior therapeutic effect. The findings might provide a novel strategy for SCI synergistic therapy and the utilization of PSA in other central nervous system diseases.

Identification of Lysophosphatidylcholines and Sphingolipids as Potential Biomarkers for Acute Aortic Dissection via Serum Metabolomics.

OBJECTIVES: Acute aortic dissection (AAD) is a severe clinical emergency with a high mortality, and is easily misdiagnosed in its early stage. This study aimed at discovering serum metabolomic markers with the potential to diagnose AAD and distinguish between two subtypes of AAD. METHODS: Thirty-five patients with AAD, including 20 with Stanford type A and 15 with Stanford type B were enrolled in this study, together with 20 healthy controls. All patients with AAD were admitted within 72 h of onset. Serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and the data were analysed by principal component analysis and partial least squares discriminant analysis. RESULTS: A total of 17 metabolites differing between the control and AAD groups were finally screened and identified as lysophosphatidylcholines (LPC) and sphingolipids including sphinganine, phytosphingosine, sphingomyelin, and ceramide. Compared with those in the healthy control group, LPC levels were significantly lower in both the Stanford type A and type B AAD groups. Interestingly, sphingolipids, including sphinganine, phytosphingosine, and ceramide, were remarkably reduced in the Stanford type A AAD group, but not in the Stanford type B AAD group. Subgroup analysis showed that the changes in LPC and sphingolipid levels were unrelated to hypertension or gender. CONCLUSIONS: The present results indicate that LPCs and sphingolipids are significantly altered in patients with AAD, and several sphingolipids, such as sphinganine, phytosphingosine, and ceramide, were dramatically decreased in patients with Stanford type A AAD. A combination of these two families of metabolites could serve as a potential biomarker for the diagnosis of AAD and distinguishing between Stanford type A and Stanford type B.

Cooperative Localization for Multi-AUVs Based on GM-PHD Filters and Information Entropy Theory.

Cooperative localization (CL) is considered a promising method for underwater localization with respect to multiple autonomous underwater vehicles (multi-AUVs). In this paper, we proposed a CL algorithm based on information entropy theory and the probability hypothesis density (PHD) filter, aiming to enhance the global localization accuracy of the follower. In the proposed framework, the follower carries lower cost navigation systems, whereas the leaders carry better ones. Meanwhile, the leaders acquire the followers' observations, including both measurements and clutter. Then, the PHD filters are utilized on the leaders and the results are communicated to the followers. The followers then perform weighted summation based on all received messages and obtain a final positioning result. Based on the information entropy theory and the PHD filter, the follower is able to acquire a precise knowledge of its position.

Applications of deep learning models in precision prediction of survival rates for heart failure patients.

BACKGROUND: Heart failure poses a significant challenge in the global health domain, and accurate prediction of mortality is crucial for devising effective treatment plans. In this study, we employed a Seq2Seq model from deep learning, integrating 12 patient features. By finely modeling continuous medical records, we successfully enhanced the accuracy of mortality prediction. OBJECTIVE: The objective of this research was to leverage the Seq2Seq model in conjunction with patient features for precise mortality prediction in heart failure cases, surpassing the performance of traditional machine learning methods. METHODS: The study utilized a Seq2Seq model in deep learning, incorporating 12 patient features, to intricately model continuous medical records. The experimental design aimed to compare the performance of Seq2Seq with traditional machine learning methods in predicting mortality rates. RESULTS: The experimental results demonstrated that the Seq2Seq model outperformed conventional machine learning methods in terms of predictive accuracy. Feature importance analysis provided critical patient risk factors, offering robust support for formulating personalized treatment plans. CONCLUSIONS: This research sheds light on the significant applications of deep learning, specifically the Seq2Seq model, in enhancing the precision of mortality prediction in heart failure cases. The findings present a valuable direction for the application of deep learning in the medical field and provide crucial insights for future research and clinical practices.

Fast adaptive focusing confocal Raman microscopy for large-area two-dimensional materials.

Large-area two-dimensional (2D) materials possess significant potential in the development of next generation semiconductor due to their unique physicochemical properties. Confocal Raman spectroscopy (CRM), a typical 2D material characterization method, has a limited effective measurement area owing to the restricted focus depth of the system and the less-than-ideal level of the substrate. We propose fast adaptive focusing confocal Raman microscopy (FAFCRM) to realize real-time focusing detection for large-area 2D materials. By observing spot changes on the charge coupled device (CCD) caused by placing an aperture in front of the CCD, the methodology gives a focusing resolution up to 100 nm per 60 µm without axial scanning. A graphene was measured over 25.6 mm × 25.6 mm area on focus through all the scanning. The research results provide new perspectives for non-destructive characterization of 2D materials at the inch level.

Association between Life's Essential 8 score and high-sensitivity C-reactive protein: A cross-sectional study from NHANES 2015-2018.

BACKGROUND: Earlier studies showed a negative correlation between life's simple 7 (LS7) and high-sensitivity C-reactive protein (hs-CRP), but no association has been found between life's essential 8 (LE8), an improved version of LS7, and hs-CRP. HYPOTHESIS: This study investigated the association between LE8 and hs-CRP utilizing data from the National Health and Nutritional Examination Survey. METHODS: A total of 7229 adults were incorporated in our study. LE8 was scored according to American Heart Association guidelines, and LE8 was divided into health behaviors and health factors. Serum samples of the participants were used to measure hs-CRP. To investigate the association between LE8 and hs-CRP, weighted linear regression, and restricted cubic spline were utilized. RESULTS: Among 7229 participants, the average age was 48.03 ± 16.88 years, 3689 (51.2%) were females and the median hs-CRP was 1.92 (0.81-4.49) mg/L. In adjusted weighted linear regression, a negative correlation was observed between the LE8 score and hs-CRP. Compared with the low LE8 score, the moderate LE8 score ß was -0.533 (-0.646 to -0.420), and the high LE8 score ß was -1.237 (-1.376 to -1.097). Health behaviors and health factors were also negatively associated with hs-CRP. In stratified analyses, the negative correlation between LE8 and hs-CRP remained consistent across subgroups. CONCLUSION: There was a negative correlation between LE8 as well as its sub-indicator scores and hs-CRP. Maintaining a positive LE8 score may be conducive to lowering the level of hs-CRP.

Sex-related association of modifiable risk factors with hypertension: A national cross-sectional study of NHANES 2007-2018.

OBJECTIVE: Sex difference is commonly observed in hypertension. We aimed to assess sex differences in the associations of modifiable lifestyle and metabolic risk factors with risk of hypertension. DESIGN: National cross-sectional population study. SETTING: Data from the 2007 to 2018 National Health and Nutrition Examination Survey. PARTICIPANTS: 7087 adults aged ≥30 years without a prior history of hypertension. PRIMARY AND SECONDARY OUTCOME MEASURES: Odds ratios and population attributable fraction (PAF) of hypertension associated with 10 modifiable risk factors: five lifestyle risk factors (current smoking, excess alcohol intake, poor diet, physical inactivity, and unhealthy sleep), and five metabolic risk factors (obesity, diabetes, dyslipidaemia, hyperuricemia, and chronic kidney disease) in women versus men. RESULTS: Compared with women, men had 84% increased risk of prevalence of hypertension. The sex difference in risk for hypertension is more evident in those aged <60 years (p for interaction <.001). For those aged <60 years the combination of lifestyle risk factors accounted for a PAF of 27.2% in men and 48.8% in women, and the combination of metabolic risk factors accounted for a PAF similarly in men (37.4%) and women (38.2%). For those aged ≥60 years, the PAF of lifestyle risk factors was similar between men and women and the metabolic risk factors accounted for a greater proportion in women (33.0% vs. 14.5% in men). CONCLUSIONS: Sex differences may exist in the relation and attribution of lifestyle and metabolic risk factors to hypertension, which may have implications for implementing sex-specific strategies to prevent hypertension.

Germ granule compartments coordinate specialized small RNA production.

Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C. elegans germ granule is compartmentalized into multiple subcompartments whose biological functions are largely unknown. Here, we identify an uncharted subcompartment of the C. elegans germ granule, which we term the E granule. The E granule is nonrandomly positioned within the germ granule. We identify five proteins that localize to the E granule, including the RNA-dependent RNA polymerase (RdRP) EGO-1, the Dicer-related helicase DRH-3, the Tudor domain-containing protein EKL-1, and two intrinsically disordered proteins, EGC-1 and ELLI-1. Localization of EGO-1 to the E granule enables synthesis of a specialized class of 22G RNAs, which derive exclusively from 5' regions of a subset of germline-expressed mRNAs. Defects in E granule assembly elicit disordered production of endogenous siRNAs, which disturbs fertility and the RNAi response. Our results define a distinct subcompartment of the C. elegans germ granule and suggest that one function of germ granule compartmentalization is to facilitate the localized production of specialized classes of small regulatory RNAs.

Nucleolar stress induces nucleolar stress body formation via the NOSR-1/NUMR-1 axis in Caenorhabditis elegans.

Environmental stimuli not only alter gene expression profiles but also induce structural changes in cells. How distinct nuclear bodies respond to cellular stress is poorly understood. Here, we identify a subnuclear organelle named the nucleolar stress body (NoSB), the formation of which is induced by the inhibition of rRNA transcription or inactivation of rRNA processing and maturation in C. elegans. NoSB does not colocalize with other previously described subnuclear organelles. We conduct forward genetic screening and identify a bZIP transcription factor, named nucleolar stress response-1 (NOSR-1), that is required for NoSB formation. The inhibition of rRNA transcription or inactivation of rRNA processing and maturation increases nosr-1 expression. By using transcriptome analysis of wild-type animals subjected to different nucleolar stress conditions and nosr-1 mutants, we identify that the SR-like protein NUMR-1 (nuclear localized metal responsive) is the target of NOSR-1. Interestingly, NUMR-1 is a component of NoSB and itself per se is required for the formation of NoSB. We conclude that the NOSR-1/NUMR-1 axis likely responds to nucleolar stress and mediates downstream stress-responsive transcription programs and subnuclear morphology alterations in C. elegans.

VEGF165 attenuates the Th17/Treg imbalance that exists when transplanting allogeneic skeletal myoblasts to treat acute myocardial infarction.

OBJECTIVES: To investigate whether Th17/Treg imbalance exists, and whether VEGF(165) attenuates the imbalance in allogeneic skeletal myoblast transplantation (allo-SMT) for acute myocardial infarction (AMI). METHODS: On days 1, 2, 4, and 7 after allo-SMT, the percentages and ratios of Th17 and Treg cells were analyzed by flow cytometry in three groups-the AMI group, the AMI-S group (allo-SMT) and the AMI-V group (with VEGF(165) treatment). Subsequently, related proinflammatory and regulatory cytokines and key transcription factors, ROR-γt mRNA and Foxp3 mRNA expression, were examined by Bio-plex and real-time polymerase chain reaction, respectively. RESULTS: On days 1, 2, 4, and 7, the percentage of Tregs, related cytokine concentrations and transcript factor Foxp3 mRNA in the AMI-S group were lower than those in the AMI group, while those in the AMI-V group were higher than those in the AMI group. However, the percentage of Th17 cells, related cytokine concentrations and ROR-γt mRNA in the AMI-S group were higher than those in the AMI group; those in the AMI-V group were lower than those in the AMI group. Compared with the AMI group, the ratios of Th17/Treg cells significantly increased in the AMI-S group and decreased in the AMI-V group. CONCLUSIONS: Th17/Treg imbalance participated in the formation and development of the inflammatory and immune response after allo-SMT. However, transfected VEGF(165) was able to relieve the severity of the Th17/Treg imbalance.

The Importance of Using Realistic 3D Canopy Models to Calculate Light Interception in the Field.

Quantifying canopy light interception provides insight into the effects of plant spacing, canopy structure, and leaf orientation on radiation distribution. This is essential for increasing crop yield and improving product quality. Canopy light interception can be quantified using 3-dimensional (3D) plant models and optical simulations. However, virtual 3D canopy models (VCMs) have often been used to quantify canopy light interception because realistic 3D canopy models (RCMs) are difficult to obtain in the field. This study aims to compare the differences in light interception between VCMs and RCM. A realistic 3D maize canopy model (RCM) was reconstructed over a large area of the field using an advanced unmanned aerial vehicle cross-circling oblique (CCO) route and the structure from motion-multi-view stereo method. Three types of VCMs (VCM-1, VCM-4, and VCM-8) were then created by replicating 1, 4, and 8 individual realistic plants constructed by CCO in the center of the corresponding RCM. The daily light interception per unit area (DLI), as computed for the 3 VCMs, exhibited marked deviation from the RCM, as evinced by the relative root mean square error (rRMSE) values of 20.22%, 17.38%, and 15.48%, respectively. Although this difference decreased as the number of plants used to replicate the virtual canopy increased, rRMSE of DLI for VCM-8 and RCM still reached 15.48%. It was also found that the difference in light interception between RCMs and VCMs was substantially smaller in the early stage (48 days after sowing [DAS]) than in the late stage (70 DAS). This study highlights the importance of using RCM when calculating light interception in the field, especially in the later growth stages of plants.

rRNA intermediates coordinate the formation of nucleolar vacuoles in C. elegans.

The nucleolus is the most prominent membraneless organelle within the nucleus. How the nucleolar structure is regulated is poorly understood. Here, we identified two types of nucleoli in C. elegans. Type I nucleoli are spherical and do not have visible nucleolar vacuoles (NoVs), and rRNA transcription and processing factors are evenly distributed throughout the nucleolus. Type II nucleoli contain vacuoles, and rRNA transcription and processing factors exclusively accumulate in the periphery rim. The NoV contains nucleoplasmic proteins and is capable of exchanging contents with the nucleoplasm. The high-order structure of the nucleolus is dynamically regulated in C. elegans. Faithful rRNA processing is important to prohibit NoVs. The depletion of 27SA2 rRNA processing factors resulted in NoV formation. The inhibition of RNA polymerase I (RNAPI) transcription and depletion of two conserved nucleolar factors, nucleolin and fibrillarin, prohibits the formation of NoVs. This finding provides a mechanism to coordinate structure maintenance and gene expression.

Investigation of the impact of supplemental reflective films to improve micro-light climate within tomato plant canopy in solar greenhouses.

The non-uniform growth and development of crops within Chinese Solar Greenhouses (CSG) is directly related to the micro-light climate within canopy. In practice, reflective films are used to improve micro-light climate within plant canopy by homogenizing light distribution and so increasing total plant light interception. However, as to our knowledge, the contributions to light distribution within canopy have not been investigated for passive reflector like reflective films. Field experiments dealing with light conditions and growth behavior over time, are complicated to carry out, time-consuming and hard to control, while however, accurate measurements of how reflective films influence the micro-light climate of canopy are an essential step to improve the growth conditions for any crop. Here, we propose a supplementary light strategy using reflective films to improve light distribution within plant canopy. Based on the example of CSG, a 3D greenhouse model including a detailed 3D tomato canopy structure was constructed to simulate the influence of supplementary reflective films to improve micro-light climate. Comparison of measured solar radiation intensity with predicted model data demonstrated that the model could precisely predict light radiation intensity over time with different time points and positions in the greenhouse. A series of reflective film configurations were investigated based on features analysis of light distribution in the tomato canopy on sunny days using the proposed model. The reflective film configuration scheme with the highest impact significantly improved the evenness of horizontal and vertical light distribution in tomato canopy. The strategy provided here can be used to configure reflective films that will enhance light conditions in CSG, which can be applied and extended in different scenarios.

Analyzing the Impact of Greenhouse Planting Strategy and Plant Architecture on Tomato Plant Physiology and Estimated Dry Matter.

Determine the level of significance of planting strategy and plant architecture and how they affect plant physiology and dry matter accumulation within greenhouses is essential to actual greenhouse plant management and breeding. We thus analyzed four planting strategies (plant spacing, furrow distance, row orientation, planting pattern) and eight different plant architectural traits (internode length, leaf azimuth angle, leaf elevation angle, leaf length, leaflet curve, leaflet elevation, leaflet number/area ratio, leaflet length/width ratio) with the same plant leaf area using a formerly developed functional-structural model for a Chinese Liaoshen-solar greenhouse and tomato plant, which used to simulate the plant physiology of light interception, temperature, stomatal conductance, photosynthesis, and dry matter. Our study led to the conclusion that the planting strategies have a more significant impact overall on plant radiation, temperature, photosynthesis, and dry matter compared to plant architecture changes. According to our findings, increasing the plant spacing will have the most significant impact to increase light interception. E-W orientation has better total light interception but yet weaker light uniformity. Changes in planting patterns have limited influence on the overall canopy physiology. Increasing the plant leaflet area by leaflet N/A ratio from what we could observe for a rose the total dry matter by 6.6%, which is significantly better than all the other plant architecture traits. An ideal tomato plant architecture which combined all the above optimal architectural traits was also designed to provide guidance on phenotypic traits selection of breeding process. The combined analysis approach described herein established the causal relationship between investigated traits, which could directly apply to provide management and breeding insights on other plant species with different solar greenhouse structures.

Celastrol protects against early brain injury after subarachnoid hemorrhage in rats through alleviating blood-brain barrier disruption and blocking necroptosis.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a life-threatening disease worldwide, and effective pharmaceutical treatment is still lacking. Celastrol is a plant-derived triterpene which showed neuroprotective potential in several types of brain insults. This study aimed to investigate the effects of celastrol on early brain injury (EBI) after SAH. METHODS: A total of sixty-one male Sprague-Dawley rats were used in this study. Rat SAH endovascular perforation model was established to mimic the pathological changes of EBI after SAH. Multiple methods such as 3.0T MRI scanning, immunohistochemistry, western blotting and propidium iodide (PI) labeling were used to explore the therapeutic effects of celastrol on SAH. RESULTS: Celastrol treatment attenuated SAH-caused brain swelling, reduced T2 lesion volume and ventricular volume in MRI scanning, and improved overall neurological score. Albumin leakage and the degradation of tight junction proteins were also ameliorated after celastrol administration. Celastrol protected blood-brain bairrer integrity through inhibiting MMP-9 expression and anti-neuroinflammatory effects. Additionally, necroptosis-related proteins RIP3 and MLKL were down-regulated and PI-positive cells in the basal cortex were less in the celastrol-treated SAH group than that in untreated SAH group. CONCLUSIONS: Celastrol exhibits neuroprotective effects on EBI after SAH and deserves to be further investigated as an add-on pharmaceutical therapy.

Effects of orientation and structure on solar radiation interception in Chinese solar greenhouse.

In order to further improve the utilization of solar energy in Chinese Solar Greenhouse (CSG), this paper systematically studied the effects of orientation and structure on solar radiation interception in CSG. A solar radiation model has been developed based on the previous research, which taking solar motion law, meteorological data, and optical properties of materials into consideration. The established model was used to optimize the orientation and structure of CSG. The analysis of structure considered two major structural parameters, which are the ridge height and the horizontal projection of the rear roof. Moreover, the widely used Liao-Shen type Chinese solar greenhouse (CSG-LS) has been taken as the prototype in the present research, and the measured data of the typical clear day was used for the model validation. The results showed that the ridge height has a remarkable influence on the solar energy captured by CSG-LS. Compared with the optimization of a single factor, the comprehensive optimization of orientation and structure can increase the solar radiation interception of the rear wall by 3.95%. Considering the limiting factor of heat storage-release capacity and the shading effect on the greenhouse structure, the optimal lighting construction of the CSG-LS (with a span of 9.0 m) was specified as 7~9° from south to west of azimuth angle, 4.5~4.7 m ridge height, and 1.4~1.6 m horizontal projection of the rear roof at 42°N latitude. The proposed solar radiation model can provide scientific guidance for the CSG-LS construction in different areas.