Decoding acute myocarditis in patients with COVID-19: Early detection through machine learning and hematological indices.

During the persistent COVID-19 pandemic, the swift progression of acute myocarditis has emerged as a profound concern due to its augmented mortality, underscoring the urgency of prompt diagnosis. This study analyzed blood samples from 5,230 COVID-19 individuals, identifying key blood and myocardial markers that illuminate the relationship between COVID-19 severity and myocarditis. A predictive model, applying Bayesian and random forest methodologies, was constructed for myocarditis' early identification, unveiling a balanced gender distribution in myocarditis cases contrary to a male predominance in COVID-19 occurrences. Particularly, older men exhibited heightened vulnerability to severe COVID-19 strains. The analysis revealed myocarditis was notably prevalent in younger demographics, and two subvariants COVID-19 progression paths were identified, characterized by symptom intensity and specific blood indicators. The enhanced myocardial marker model displayed remarkable diagnostic accuracy, advocating its valuable application in future myocarditis detection and treatment strategies amidst the COVID-19 crisis.

Economic tolerance design of the P2 raceway based on the quasi-static model of aerospace ball bearings.

This study focused on designing the raceway tolerance of high-precision rolling bearings. After the tolerance error equivalence relationship is defined, the application of the rolling bearing error equalization effect in tolerance design is studied. First, a five-degree of freedom quasi-static model was established for angular contact ball bearings. The waviness was included in the manufacturing error, and the radial and axial runouts of the bearing inner ring were calculated. Second, the error homogenization effect of the rolling bearing was studied, and the error homogenization coefficient was defined. The results of the study demonstrated that the bearing rotary accuracy was higher than the raceway error by an order of magnitude. Third, the manufacturing error range of each precision grade of the rolling bearing raceway was obtained by investigating errors of the equalization coefficient. Finally, the specific value of the raceway tolerance of P2 rolling bearings was obtained.

ABLs and TMKs are co-receptors for extracellular auxin.

Extracellular perception of auxin, an essential phytohormone in plants, has been debated for decades. Auxin-binding protein 1 (ABP1) physically interacts with quintessential transmembrane kinases (TMKs) and was proposed to act as an extracellular auxin receptor, but its role was disputed because abp1 knockout mutants lack obvious morphological phenotypes. Here, we identified two new auxin-binding proteins, ABL1 and ABL2, that are localized to the apoplast and directly interact with the extracellular domain of TMKs in an auxin-dependent manner. Furthermore, functionally redundant ABL1 and ABL2 genetically interact with TMKs and exhibit functions that overlap with those of ABP1 as well as being independent of ABP1. Importantly, the extracellular domain of TMK1 itself binds auxin and synergizes with either ABP1 or ABL1 in auxin binding. Thus, our findings discovered auxin receptors ABL1 and ABL2 having functions overlapping with but distinct from ABP1 and acting together with TMKs as co-receptors for extracellular auxin.

The plant-unique protein DRIF1 coordinates with sorting nexin 1 to regulate membrane protein homeostasis.

Membrane protein homeostasis is fine-tuned by the cellular pathways for vacuolar degradation and recycling, which ultimately facilitate plant growth and cell-environment interactions. The endosomal sorting complex required for transport (ESCRT) machinery plays important roles in regulating intraluminal vesicle (ILV) formation and membrane protein sorting to vacuoles. We previously showed that the plant-specific ESCRT component FYVE DOMAIN PROTEIN REQUIRED FOR ENDOSOMAL SORTING1 (FREE1) performs multiple functions in plants, although the underlying mechanisms remain elusive. In this study, we performed a suppressor screen of the FREE1-RNAi mutant and identified and characterized 2 suppressor of free1 (sof) mutants in Arabidopsis (Arabidopsis thaliana). These mutants, sof10 and sof641, result in a premature stop codon or a missense mutation in AT5G10370, respectively. This gene was named DEAH and RING domain-containing protein as FREE1 suppressor 1 (DRIF1). DRIF1 has a homologous gene, DRIF2, in the Arabidopsis genome with 95% identity to DRIF1. The embryos of drif1 drif2 mutants arrested at the globular stage and formed enlarged multivesicular bodies (MVBs) with an increased number of ILVs. DRIF1 is a membrane-associated protein that coordinates with retromer component sorting nexin 1 to regulate PIN-FORMED2 recycling to the plasma membrane. Altogether, our data demonstrate that DRIF1 is a unique retromer interactor that orchestrates FREE1-mediated ILV formation of MVBs and vacuolar sorting of membrane proteins for degradation in plants.

3D Dirac semimetal supported thermal tunable terahertz hybrid plasmonic waveguides.

By depositing the trapezoidal dielectric stripe on top of the 3D Dirac semimetal (DSM) hybrid plasmonic waveguide, the thermal tunable propagation properties have been systematically investigated in the terahertz regime, taking into account the influences of the structure of the dielectric stripe, temperature and frequency. The results manifest that as the upper side width of the trapezoidal stripe increases, the propagation length and figure of merit (FOM) both decrease. The propagation properties of hybrid modes are closely associated with temperature, in that when the temperature changes in the scope of 3-600 K, the modulation depth of propagation length is more than 96%. Additionally, at the balance point of plasmonic and dielectric modes, the propagation length and FOM manifest strong peaks and indicate an obvious blue shift with the increase of temperature. Furthermore, the propagation properties can be improved significantly with a Si-SiO2 hybrid dielectric stripe structure, e.g., on the condition that the Si layer width is 5 µm, the maximum value of the propagation length reaches more than 6.46 × 105 µm, which is tens of times larger than those pure SiO2 (4.67 × 104 µm) and Si (1.15 × 104 µm) stripe. The results are very helpful for the design of novel plasmonic devices, such as cutting-edge modulator, lasers and filters.

Apicosome: Newly identified cell-type-specific organelle in mouse cochlear and vestibular hair cells.

Cochlear and vestibular hair cells are highly specialized sensory receptors for hearing and balance. Here, we report a serendipitous identification of a hair-cell-specific organelle in neonatal mouse inner ear, which we name "apicosome." The apicosome is ∼500 nm in diameter and shows itinerant nature and transient appearance during development in cochlear hair cells. In contrast to cochlear hair cells, the apicosome persists in vestibular hair cells even in adult. The timing of apicosome translocation and disappearance in cochlear hair cells during development is correlated with kinocilium development and maintenance. The apicosome is not seen in supporting cells despite the fact that nascent supporting cells have microvilli and a primary cilium. Interestingly, transdifferentiated hair cells from supporting cells also contain apicosome, suggesting that it is unique to hair cells. Thus, our study identifies a previously undescribed organelle in hair cells and lays the foundation for further characterization of this specialized structure.

Identification and functional characterization of the dirigent gene family in Phryma leptostachya and the contribution of PlDIR1 in lignan biosynthesis.

BACKGROUND: Furofuran lignans, the main insecticidal ingredient in Phryma leptostachya, exhibit excellent controlling efficacy against a variety of pests. During the biosynthesis of furofuran lignans, Dirigent proteins (DIRs) are thought to be dominant in the stereoselective coupling of coniferyl alcohol to form ( ±)-pinoresinol. There are DIR family members in almost every vascular plant, but members of DIRs in P. leptostachya are unknown. To identify the PlDIR genes and elucidate their functions in lignan biosynthesis, this study performed transcriptome-wide analysis and characterized the catalytic activity of the PlDIR1 protein. RESULTS: Fifteen full-length unique PlDIR genes were identified in P. leptostachya. A phylogenetic analysis of the PlDIRs classified them into four subfamilies (DIR-a, DIR-b/d, DIR-e, and DIR-g), and 12 conserved motifs were found among them. In tissue-specific expression analysis, except for PlDIR7, which displayed the highest transcript abundance in seeds, the other PlDIRs showed preferential expression in roots, leaves, and stems. Furthermore, the treatments with signaling molecules demonstrated that PlDIRs could be significantly induced by methyl jasmonate (MeJA), salicylic acid (SA), and ethylene (ETH), both in the roots and leaves of P. leptostachya. In examining the tertiary structure of the protein and the critical amino acids, it was found that PlDIR1, one of the DIR-a subfamily members, might be involved in the region- and stereo-selectivity of the phenoxy radical. Accordingly, LC-MS/MS analysis demonstrated the catalytic activity of recombinant PlDIR1 protein from Escherichia coli to direct coniferyl alcohol coupling into ( +)-pinoresinol. The active sites and hydrogen bonds of the interaction between PlDIR1 and bis-quinone methide (bisQM), the intermediate in ( +)-pinoresinol formation, were analyzed by molecular docking. As a result, 18 active sites and 4 hydrogen bonds (Asp-42, Ala-113, Leu-138, Arg-143) were discovered in the PlDIR1-bisQM complex. Moreover, correlation analysis indicated that the expression profile of PlDIR1 was closely connected with lignan accumulations after SA treatment. CONCLUSIONS: The results of this study will provide useful clues for uncovering P. leptostachya's lignan biosynthesis pathway as well as facilitate further studies on the DIR family.

Retrograde transport in plants: Circular economy in the endomembrane system.

The study of endomembrane trafficking is crucial for understanding how cells and whole organisms function. Moreover, there is a special interest in investigating endomembrane trafficking in plants, given its role in transport and accumulation of seed storage proteins and in secretion of cell wall material, arguably the two most essential commodities obtained from crops. The mechanisms of anterograde transport in the biosynthetic and endocytic pathways of plants have been thoroughly discussed in recent reviews, but, comparatively, retrograde trafficking pathways have received less attention. Retrograde trafficking is essential to recover membranes, retrieve proteins that have escaped from their intended localization, maintain homeostasis in maturing compartments, and recycle trafficking machinery for its reuse in anterograde transport reactions. Here, we review the current understanding on retrograde trafficking pathways in the endomembrane system of plants, discussing their integration with anterograde transport routes, describing conserved and plant-specific retrieval mechanisms at play, highlighting contentious issues and identifying open questions for future research.

The plant unique ESCRT component FREE1 regulates autophagosome closure.

The energy sensor AMP-activated protein kinase (AMPK) can activate autophagy when cellular energy production becomes compromised. However, the degree to which nutrient sensing impinges on the autophagosome closure remains unknown. Here, we provide the mechanism underlying a plant unique protein FREE1, upon autophagy-induced SnRK1α1-mediated phosphorylation, functions as a linkage between ATG conjugation system and ESCRT machinery to regulate the autophagosome closure upon nutrient deprivation. Using high-resolution microscopy, 3D-electron tomography, and protease protection assay, we showed that unclosed autophagosomes accumulated in free1 mutants. Proteomic, cellular and biochemical analysis revealed the mechanistic connection between FREE1 and the ATG conjugation system/ESCRT-III complex in regulating autophagosome closure. Mass spectrometry analysis showed that the evolutionary conserved plant energy sensor SnRK1α1 phosphorylates FREE1 and recruits it to the autophagosomes to promote closure. Mutagenesis of the phosphorylation site on FREE1 caused the autophagosome closure failure. Our findings unveil how cellular energy sensing pathways regulate autophagosome closure to maintain cellular homeostasis.

Flexible and Stretchable Carbon-Based Sensors and Actuators for Soft Robots.

In recent years, the emergence of low-dimensional carbon-based materials, such as carbon dots, carbon nanotubes, and graphene, together with the advances in materials science, have greatly enriched the variety of flexible and stretchable electronic devices. Compared with conventional rigid devices, these soft robotic sensors and actuators exhibit remarkable advantages in terms of their biocompatibility, portability, power efficiency, and wearability, thus creating myriad possibilities of novel wearable and implantable tactile sensors, as well as micro-/nano-soft actuation systems. Interestingly, not only are carbon-based materials ideal constituents for photodetectors, gas, thermal, triboelectric sensors due to their geometry and extraordinary sensitivity to various external stimuli, but they also provide significantly more precise manipulation of the actuators than conventional centimeter-scale pneumatic and hydraulic robotic actuators, at a molecular level. In this review, we summarize recent progress on state-of-the-art flexible and stretchable carbon-based sensors and actuators that have creatively added to the development of biomedicine, nanoscience, materials science, as well as soft robotics. In the end, we propose the future potential of carbon-based materials for biomedical and soft robotic applications.

Ufmylation reconciles salt stress-induced unfolded protein responses via ER-phagy in Arabidopsis.

In plants, the endomembrane system is tightly regulated in response to environmental stresses for maintaining cellular homeostasis. Autophagosomes, the double membrane organelles forming upon nutrient deprivation or stress induction, degrade bulky cytosolic materials for nutrient turnover. Though abiotic stresses have been reported to induce plant autophagy, few receptors or regulators for selective autophagy have been characterized for specific stresses. Here, we have applied immunoprecipitation followed by tandem mass spectrometry using the autophagosome marker protein ATG8 as bait and have identified the E3 ligase of the ufmylation system Ufl1 as a bona fide ATG8 interactor under salt stress. Notably, core components in the ufmylation cascade, Ufl1 and Ufm1, interact with the autophagy kinase complexes proteins ATG1 and ATG6. Cellular and genetic analysis showed that Ufl1 is important for endoplasmic reticulum (ER)-phagy under persisting salt stress. Loss-of-function mutants of Ufl1 display a salt stress hypersensitive phenotype and abnormal ER morphology. Prolonged ER stress responses are detected in ufl1 mutants that phenocopy the autophagy dysfunction atg5 mutants. Consistently, expression of ufmylation cascade components is up-regulated by salt stress. Taken together, our study demonstrates the role of ufmylation in regulating ER homeostasis under salt stress through ER-phagy.

Incorporation of Suppression of Tumorigenicity 2 into Random Survival Forests for Enhancing Prediction of Short-Term Prognosis in Community-ACQUIRED Pneumonia.

(1) Background: Biomarker and model development can help physicians adjust the management of patients with community-acquired pneumonia (CAP) by screening for inpatients with a low probability of cure early in their admission; (2) Methods: We conducted a 30-day cohort study of newly admitted adult CAP patients over 20 years of age. Prognosis models to predict the short-term prognosis were developed using random survival forest (RSF) method; (3) Results: A total of 247 adult CAP patients were studied and 208 (84.21%) of them reached clinical stability within 30 days. The soluble form of suppression of tumorigenicity-2 (sST2) was an independent predictor of clinical stability and the addition of sST2 to the prognosis model could improve the performance of the prognosis model. The C-index of the RSF model for predicting clinical stability was 0.8342 (95% CI, 0.8086-0.8598), which is higher than 0.7181 (95% CI, 0.6933-0.7429) of CURB 65 score, 0.8025 (95% CI, 0.7776-8274) of PSI score, and 0.8214 (95% CI, 0.8080-0.8348) of cox regression. In addition, the RSF model was associated with adverse clinical events during hospitalization, ICU admissions, and short-term mortality; (4) Conclusions: The RSF model by incorporating sST2 was more accurate than traditional methods in assessing the short-term prognosis of CAP patients.

The plant ESCRT component FREE1 regulates peroxisome-mediated turnover of lipid droplets in germinating Arabidopsis seedlings.

Lipid droplets (LDs) stored during seed development are mobilized and provide essential energy and lipids to support seedling growth upon germination. Triacylglycerols (TAGs) are the main neutral lipids stored in LDs. The lipase SUGAR DEPENDENT 1 (SDP1), which hydrolyzes TAGs in Arabidopsis thaliana, is localized on peroxisomes and traffics to the LD surface through peroxisomal extension, but the underlying mechanism remains elusive. Here, we report a previously unknown function of a plant-unique endosomal sorting complex required for transport (ESCRT) component FYVE DOMAIN PROTEIN REQUIRED FOR ENDOSOMAL SORTING 1 (FREE1) in regulating peroxisome/SDP1-mediated LD turnover in Arabidopsis. We showed that LD degradation was impaired in germinating free1 mutant; moreover, the tubulation of SDP1- or PEROXIN 11e (PEX11e)-marked peroxisomes and the migration of SDP1-positive peroxisomes to the LD surface were altered in the free1 mutant. Electron tomography analysis showed that peroxisomes failed to form tubules to engulf LDs in free1, unlike in the wild-type. FREE1 interacted directly with both PEX11e and SDP1, suggesting that these interactions may regulate peroxisomal extension and trafficking of the lipase SDP1 to LDs. Taken together, our results demonstrate a pivotal role for FREE1 in LD degradation in germinating seedlings via regulating peroxisomal tubulation and SDP1 targeting.

Correlation of vacuole morphology with stomatal lineage development by whole-cell electron tomography.

Stomatal movement is essential for plants to optimize transpiration and therefore photosynthesis. Rapid changes in the stomatal aperture are accompanied by adjustment of vacuole volume and morphology in guard cells (GCs). In Arabidopsis (Arabidopsis thaliana) leaf epidermis, stomatal development undergoes a cell-fate transition including four stomatal lineage cells: meristemoid, guard mother cell, young GC, and GC. Little is known about the mechanism underlying vacuole dynamics and vacuole formation during stomatal development. Here, we utilized whole-cell electron tomography (ET) analysis to elucidate vacuole morphology, formation, and development in different stages of stomatal lineage cells at nanometer resolution. The whole-cell ET models demonstrated that large vacuoles were generated from small vacuole stepwise fusion/maturation along stomatal development stages. Further ET analyses verified the existence of swollen intraluminal vesicles inside distinct vacuoles at certain developmental stages of stomatal lineage cells, implying a role of multivesicular body fusion in stomatal vacuole formation. Collectively, our findings demonstrate a mechanism mediating vacuole formation in Arabidopsis stomatal development and may shed light on the role of vacuoles in stomatal movement.

Electric field induced macroscopic cellular phase of nanoparticles.

A suspension of nanoparticles with very low volume fraction is found to assemble into a macroscopic cellular phase that is composed of particle-rich walls and particle-free voids under the collective influence of AC and DC voltages. Systematic study of this phase transition shows that it was the result of electrophoretic assembly into a two-dimensional configuration followed by spinodal decomposition into particle-rich walls and particle-poor cells mediated principally by electrohydrodynamic flow. This mechanistic understanding reveals two characteristics needed for a cellular phase to form, namely (1) a system that is considered two dimensional and (2) short-range attractive, long-range repulsive interparticle interactions. In addition to determining the mechanism underpinning the formation of the cellular phase, this work presents a method to reversibly assemble microscale continuous structures out of nanoscale particles in a manner that may enable the creation of materials that impact diverse fields including energy storage and filtration.

A distinct giant coat protein complex II vesicle population in Arabidopsis thaliana.

Plants live as sessile organisms with large-scale gene duplication events and subsequent paralogue divergence during evolution. Notably, plant paralogues are expressed tissue-specifically and fine-tuned by phytohormones during various developmental processes. The coat protein complex II (COPII) is a highly conserved vesiculation machinery mediating protein transport from the endoplasmic reticulum to the Golgi apparatus in eukaryotes1. Intriguingly, Arabidopsis COPII paralogues greatly outnumber those in yeast and mammals2-6. However, the functional diversity and underlying mechanism of distinct COPII paralogues in regulating protein endoplasmic reticulum export and coping with various adverse environmental stresses are poorly understood. Here we characterize a novel population of COPII vesicles produced in response to abscisic acid, a key phytohormone regulating abiotic stress responses in plants. These hormone-induced giant COPII vesicles are regulated by an Arabidopsis-specific COPII paralogue and carry stress-related channels/transporters for alleviating stresses. This study thus provides a new mechanism underlying abscisic acid-induced stress responses via the giant COPII vesicles and answers a long-standing question on the evolutionary significance of gene duplications in Arabidopsis.

A plant-unique ESCRT component, FYVE4, regulates multivesicular endosome biogenesis and plant growth.

During evolution, land plants generated unique proteins that participate in endosomal sorting and multivesicular endosome (MVE) biogenesis, many of them with specific phosphoinositide-binding capabilities. Nonetheless, the function of most plant phosphoinositide-binding proteins in endosomal trafficking remains elusive. Here, we analysed several Arabidopsis mutants lacking predicted phosphoinositide-binding proteins and first identified fyve4-1 as a mutant with a hypersensitive response to high-boron conditions and defects in degradative vacuolar sorting of membrane proteins such as the borate exporter BOR1-GFP. FYVE4 encodes a plant-unique, FYVE domain-containing protein that interacts with SNF7, a core component of ESCRT-III (Endosomal Sorting Complex Required for Transport III). FYVE4 affects the membrane association of the late-acting ESCRT components SNF7 and VPS4, and modulates the formation of intraluminal vesicles (ILVs) inside MVEs. The critical function of FYVE4 in the ESCRT pathway was further demonstrated by the strong genetic interactions with SNF7B and LIP5. Although the fyve4-1, snf7b and lip5 single mutants were viable, the fyve4-1 snf7b and fyve4-1 lip5 double mutants were seedling lethal, with strong defects in MVE biogenesis and vacuolar sorting of ubiquitinated membrane proteins. Taken together, we identified FYVE4 as a novel plant endosomal regulator, which functions in ESCRTing pathway to regulate MVE biogenesis.

Massively parallel cantilever-free atomic force microscopy.

Resolution and field-of-view often represent a fundamental tradeoff in microscopy. Atomic force microscopy (AFM), in which a cantilevered probe deflects under the influence of local forces as it scans across a substrate, is a key example of this tradeoff with high resolution imaging being largely limited to small areas. Despite the tremendous impact of AFM in fields including materials science, biology, and surface science, the limitation in imaging area has remained a key barrier to studying samples with intricate hierarchical structure. Here, we show that massively parallel AFM with >1000 probes is possible through the combination of a cantilever-free probe architecture and a scalable optical method for detecting probe-sample contact. Specifically, optically reflective conical probes on a comparatively compliant film are found to comprise a distributed optical lever that translates probe motion into an optical signal that provides sub-10 nm vertical precision. The scalability of this approach makes it well suited for imaging applications that require high resolution over large areas.

Theory for hierarchical assembly with dielectrophoresis and the role of particle anisotropy.

Nonuniform electric fields cause polarizable particles to move through an effect known as dielectrophoresis (DEP). Additionally, the particles themselves create nonuniform fields due to their induced dipoles. When the nonuniform field of one particle causes another to move, it represents a path to hierarchical assembly termed mutual DEP (mDEP). Anisotropic particles potentially provide further opportunities for assembly through intense and intricate local field profiles. Here, we construct a theoretical framework for describing anisotropic particles as templates for assembly through mDEP by considering the motion of small nanoparticles near larger anisotropic nanoparticles. Using finite element analysis, we study eight particle shapes and compute their field enhancement and polarizability in an orientation-specific manner. Strikingly, we find a more than tenfold enhancement in the field near certain particle shapes, potentially promoting mDEP. To more directly relate the field intensity to the anticipated assembly outcome, we compute the volume experiencing each field enhancement versus particle shape and orientation. Finally, we provide a framework for predicting how mixtures of two distinct particle species will begin to assemble in a manner that allows for the identification of conditions that kinetically bias assembly toward specific hierarchical outcomes.

Identification and characterization of unconventional membrane protein trafficking regulators in Arabidopsis: A genetic approach.

Proper trafficking and subcellular localization of membrane proteins are essential for plant growth and development. The plant endomembrane system contains several membrane-bound organelles with distinct functions including the endoplasmic reticulum (ER), Golgi apparatus, trans-Golgi network (TGN) or early endosome, prevacuolar compartment (PVC) or multivesicular body (MVB) and vacuole. Multiple approaches have been successfully used to identify and study the regulators and components important for signal transduction, growth and development, as well as membrane trafficking in the endomembrane system in plants. These include the homologous characterization of the counterparts in mammals or yeast employing both reverse genetic as well as the forward genetic screen approaches. However, the deletion or mutation of membrane trafficking related proteins usually leads to seedling lethality due to their essential roles in plant development and organelle biogenesis. To overcome the limitation of lethal phenotype of the target proteins, we used DEX-inducible RNAi knock-down lines to study their function in plants. More recently, we developed and used both RNAi knock-down and T-DNA insertional lines as starting materials to screen for mutations that could suppress and rescue the lethal phenotype, or a suppressor screening. Further characterization of the newly identified suppressor mutants has resulted in the identification of novel negative regulators in mediating membrane trafficking and organelle biogenesis in plants. In this review, we summarize the current approaches in studying protein trafficking in the endomembrane system. We then describe three examples of suppressor screening with distinct starting materials (i.e. FREE1, MON1, and SH3P2 that are regulators of MVB, vacuole, and autophagosomes, respectively) to discuss the rationale, procedures, advantages and disadvantages, and possible outcomes of such a suppressor screening. We finally propose that these novel screening approaches will lead to the identification of new unconventional players in regulating protein trafficking and organelle biogenesis in plants and discuss their impact on plant cell biology research.