Maternal nitric oxide homeostasis impacts female gametophyte development under optimal and stress conditions.

In adverse environments, the number of fertilizable female gametophytes (FGs) in plants is reduced, leading to increased survival of the remaining offspring. How the maternal plant perceives internal growth cues and external stress conditions to alter FG development remains largely unknown. We report that homeostasis of the stress signaling molecule nitric oxide (NO) plays a key role in controlling FG development under both optimal and stress conditions. NO homeostasis is precisely regulated by S-nitrosoglutathione reductase (GSNOR). Prior to fertilization, GSNOR protein is exclusively accumulated in sporophytic tissues and indirectly controls FG development in Arabidopsis (Arabidopsis thaliana). In GSNOR null mutants, NO species accumulated in the degenerating sporophytic nucellus, and auxin efflux into the developing FG was restricted, which inhibited FG development, resulting in reduced fertility. Importantly, restoring GSNOR expression in maternal, but not gametophytic tissues, or increasing auxin efflux substrate significantly increased the proportion of normal FGs and fertility. Furthermore, GSNOR overexpression or added auxin efflux substrate increased fertility under drought and salt stress. These data indicate that NO homeostasis is critical to normal auxin transport and maternal control of FG development, which in turn determine seed yield. Understanding this aspect of fertility control could contribute to mediating yield loss under adverse conditions.

Design of a refractive-metasurface hybrid annular aperture folded optical system.

Folded lenses offer advantages in terms of lightness and thinness, but they have limitations when it comes to correcting aberrations. In this paper, we propose a novel approach to address this issue by incorporating metasurfaces in the design of folded optical systems. Specifically, a folded refractive-metasurface hybrid annular aperture folded lens (AFL) is introduced. The structural characteristics of the AFL imaging system are analyzed to investigate the blocking ratio, thickness, and light collection capability of the ring aperture system. Additionally, a hybrid optical integration design using Zemax software is proposed for the metasurfaces. A quadruple-folded AFL working in the mid-infrared waveband is then designed. The superstructure surface is analyzed, and its processability is discussed. The results demonstrate that the reflective-metasurface hybrid AFL significantly improves the imaging quality of this type of optical system while meeting the required design accuracy.

Modulation of macrophages by a phillyrin-loaded thermosensitive hydrogel promotes skin wound healing in mice.

BACKGROUND: Impaired wound healing in traumatic skin injuries remains a severe clinical challenge due to impaired re-vascularization, harmful bacteria infection, and inflammation dysregulation. Macrophages are recognized as prominent immune cells in tissue regeneration and wound healing. Consequently, the modulation of macrophages provides a promising therapeutic target for wound healing disorders. Here, we aimed to explore whether a novel constructed combination of thermosensitive hydrogel Pluronic F-127 (PF-127) and phillyrin (PH, the main active compound of forsythia suspensa) could improve skin wound healing. METHODS: Firstly, the biological effects of pH on the phenotype and inflammation of macrophages were assessed by flow cytometry and ELISA. The biocompatibility of the PF-127 plus PH combination was investigated on keratinocytes and red blood cells. The biological effect of PF-127/PH hydrogel on the migratory ability of keratinocytes in vitro was evaluated using the scratch and transwell migration assays. In addition,S. aureusandE. coliwere employed to test the antibacterial properties of the PF-127 plus PH combination. Finally, PF-127 plus PH scaffold was appliedto the full-thickness skin defect in mice. Histomorphological evaluation and immunochemistry were performed to explore the wound-healing activity of PF-127/PH hydrogel. RESULTS: PH can promote the polarization of macrophages from the M1 (pro-inflammatory) phenotype to the M2 (anti-inflammatory) phenotype. The PF-127/PH hydrogel was highly biocompatible and showed a potent stimulative effect on the migration of keratinocytesin vitro. The combination of PF-127 and PH exerted a pronounced antibacterial activity onS. aureusandE. coli in vitro.PF-127/PH hydrogel potently accelerates the healing of full-thickness skin defects by promoting skin cell proliferation, accelerating angiogenesis, and inhibiting inflammation. CONCLUSIONS: Our study suggests that PF-127/PH hydrogel has excellent potential for treating traumatic skin defects.

Design, synthesis and glycosidase inhibition of DAB derivatives with C-4 peptide and dipeptide branches.

A series of DAB-peptide and DAB-dipeptide derivatives were synthesized from D-tartrate-derived nitrone 18. The DAB peptides 16 are derivatives of trans,trans-3,4-dihydroxy-L-proline. Glycosidase inhibition assay found four of them to be weak and selective bovine liver ß-galactosidase inhibitors, and the C-2' methyl substituted compound 23b showed the most potent ß-galactosidase inhibition (IC50 = 0.66 µM). Molecular docking studies revealed different docking modes of compound 23b compared to those of other DAB-peptides, and partial similarity of compound 23b to DGJ.

Trends of mental health care utilization among US adults from 1999 to 2018.

BACKGROUND: Mental health disorders affect millions of US adults, however, the trends and related factors for mental health care utilization in the US remain unknown. AIMS: Our study aimed to assess the trend of mental health utilization and related socio-demographic factors in the US. METHODS: The study included 55,052 individuals from the National Health and Nutrition Examination Survey (NHANES) in 1999-2018. Temporal trends in the percentages of mental health care utilizers were estimated across survey cycles. Trends and linked factors of mental health care utilization were assessed by a logistic regression model, while the non-linearity was estimated by restricted cubic splines. RESULTS: From 1999 to 2018, the percentage of mental health care utilizers in the US adult population increased from 7.0 to 11.3% (P < 0.001); meanwhile, the trends in males and females were consistent. The percentage increased positively with age in individuals aged 20-39 (P < 0.001) or aged 60 and over (P = 0.003). The trends were consistent in three race/ethnicity groups (P < 0.05). The logistic regression analysis revealed that several disparities existed in the subpopulations. Older age, female, lower family poverty-income ratio (PIR), chronic diseases, higher educational level, and smoking were estimated to be associated with a higher percentage of mental health care. CONCLUSIONS: The percentage of mental health care utilizers took on an increasing trend in the US adult population from 1999 to 2018. These trends were also observed in the subpopulations, but with disparities. Future research for exploring factors associated with mental health care utilizations is necessary.

Diastereoselective Synthesis, Glycosidase Inhibition, and Docking Study of C-7-Fluorinated Casuarine and Australine Derivatives.

C-7-fluorinated derivatives of two important polyhydroxylated pyrrolizidines, casuarine and australine, were synthesized with organocatalytic stereoselective α-fluorination of aldehydes as the key step. The strategy is extensively applicable to some synthetically challenging fluorinated iminosugars and carbohydrates. The docking studies indicated that the potent inhibitions of trehalase and amyloglucosidase by the fluorinated polyhydroxylated pyrrolizidines are due to the interaction modes dominated by fluorine atoms in these iminosugars with the amino acids' residues of the corresponding enzymes. Steady interactions were established between the C-7 fluoride and a hydrophobic pocket in amyloglucosidase by untypical anion-π interactions. These unexpected docking modes and related structure-activity relationship studies emphasize the value of fluorination in the design of polyhydroxylated pyrrolizidine glycosidase inhibitors.

BRS1 mediates plant redox regulation and cold responses.

BACKGROUND: Brassinosteroid-insensitive 1 suppressor 1 (BRS1) is a serine carboxypeptidase that mediates brassinosteroid signaling and participates in multiple developmental processes in Arabidopsis. However, little is known about the precise role of BRS1 in this context. RESULTS: In this study, we analyzed transcriptional and proteomic profiles of Arabidopsis seedlings overexpressing BRS1 and found that this gene was involved in both cold stress responses and redox regulation. Further proteomic evidence showed that BRS1 regulated cell redox by indirectly interacting with cytosolic NADP + -dependent isocitrate dehydrogenase (cICDH). One novel alternative splice form of BRS1 was identified in over-expression mutants brs1-1D, which may confer a new role in plant development and stress responses. CONCLUSIONS: This study highlights the role of BRS1 in plant redox regulation and stress responses, which extends our understanding of extracellular serine carboxypeptidases.

Auxin efflux controls orderly nucellar degeneration and expansion of the female gametophyte in Arabidopsis.

The nucellus tissue in flowering plants provides nutrition for the development of the female gametophyte (FG) and young embryo. The nucellus degenerates as the FG develops, but the mechanism controlling the coupled process of nucellar degeneration and FG expansion remains largely unknown. The degeneration process of the nucellus and spatiotemporal auxin distribution in the developing ovule before fertilization were investigated in Arabidopsis thaliana. Nucellar degeneration before fertilization occurs through vacuolar cell death and in an ordered degeneration fashion. This sequential nucellar degeneration is controlled by the signalling molecule auxin. Auxin efflux plays the core role in precisely controlling the spatiotemporal pattern of auxin distribution in the nucellus surrounding the FG. The auxin efflux carrier PIN1 transports maternal auxin into the nucellus while PIN3/PIN4/PIN7 further delivers auxin to degenerating nucellar cells and concurrently controls FG central vacuole expansion. Notably, auxin concentration and auxin efflux are controlled by the maternal tissues, acting as a key communication from maternal to filial tissue.

Stereocomplementary synthesis of casuarine and its 6-epi-, 7-epi-, and 6,7-diepi-stereoisomers.

Four diastereomers belonging to the family of casuarines, including casuarine (1), 6-epi-casuarine (2), 7-epi-casuarine (13) and 6,7-diepi-casuarine (14), have been synthesized from D-arabinose-derived cyclic nitrone 7 and nitrone-derived aldehyde 4 by a stereocomplementary strategy. Glycosidase inhibition comparison showed that 6-epi-casuarine (2) exhibits enhanced inhibition of trehalase (IC50 = 9.7 µM) and 6,7-diepi-casuarine (14) leads to specific inhibition of trehalase.

The Orally Active Noncompetitive AMPAR Antagonist Perampanel Attenuates Focal Cerebral Ischemia Injury in Rats.

Inhibition of ionotropic glutamate receptors (iGluRs) is a potential target of therapy for ischemic stroke. Perampanel is a potent noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) antagonist with good oral bioavailability and favorable pharmacokinetic properties. Here, we investigated the potential protective effects of perampanel against focal cerebral ischemia in a middle cerebral artery occlusion (MCAO) model in rats. Oral administration with perampanel significantly reduced MCAO-induced brain edema, brain infarct volume, and neuronal apoptosis. These protective effects were associated with improved functional outcomes, as measured by foot-fault test, adhesive removal test, and modified neurological severity score (mNSS) test. Importantly, perampanel was effective even when the administration was delayed to 1 h after reperfusion. The results of enzyme-linked immunosorbent assay (ELISA) showed that perampanel significantly decreased the expression of pro-inflammatory cytokines IL-1ß and TNF-α, whereas it increased the levels of anti-inflammatory cytokines IL-10 and TGF-ß1 after MCAO. In addition, perampanel treatment markedly decreased the expression of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS), and also inhibited nitric oxide (NO) generation in MCAO-injured rats at 24 and 72 h after reperfusion. In conclusion, this study demonstrated that the orally active AMPAR antagonist perampanel protects against experimental ischemic stroke via regulating inflammatory cytokines and NOS pathways.

Precise and low-power closed-loop neuromodulation through algorithm-integrated circuit co-design.

Implantable neuromodulation devices have significantly advanced treatments for neurological disorders such as Parkinson's disease, epilepsy, and depression. Traditional open-loop devices like deep brain stimulation (DBS) and spinal cord stimulators (SCS) often lead to overstimulation and lack adaptive precision, raising safety and side-effect concerns. Next-generation closed-loop systems offer real-time monitoring and on-device diagnostics for responsive stimulation, presenting a significant advancement for treating a range of brain diseases. However, the high false alarm rates of current closed-loop technologies limit their efficacy and increase energy consumption due to unnecessary stimulations. In this study, we introduce an artificial intelligence-integrated circuit co-design that targets these issues and using an online demonstration system for closed-loop seizure prediction to showcase its effectiveness. Firstly, two neural network models are obtained with neural-network search and quantization strategies. A binary neural network is optimized for minimal computation with high sensitivity and a convolutional neural network with a false alarm rate as low as 0.1/h for false alarm rejection. Then, a dedicated low-power processor is fabricated in 55 nm technology to implement the two models. With reconfigurable design and event-driven processing feature the resulting application-specific integrated circuit (ASIC) occupies only 5mm2 silicon area and the average power consumption is 142 µW. The proposed solution achieves a significant reduction in both false alarm rates and power consumption when benchmarked against state-of-the-art counterparts.

Combinational Intercalation-Conversion-Intercalation reaction of CuInS2@PPy anode for Sodium-Ion batteries.

Polypyrrole-coated CuInS2 (CuInS2@PPy) composite was prepared through the chemical vapor transport method and subsequent in situ polymerized coating strategy. In this unique nanoarchitecture, the PPy coating layer plays a crucial role in improving the conductivity of the composite, suppressing the volume change of CuInS2, and maintaining the structural integrity of electrode material upon cycling. In addition, the electrochemical reaction mechanism and kinetics of CuInS2@PPy were investigated in-depth. Benefitting from the synergism of its combinational intercalation-conversion-intercalation reaction mechanism and the high conductivity of the PPy coating layer, CuInS2@PPy electrode exhibits superior rate capability and cycling stability for sodium-ion batteries, with a capacity of 404.8 mA h g-1 at 4 A g-1 over 2500 cycles.

Construction of heterostructured Fe2O3/Fe7S8 hollow fibers to boost the electrochemical kinetics of lithium storage.

Heterostructured Fe2O3/Fe7S8 hollow fibers were rationally designed and synthesized via the electrospinning technique, followed by a calcination process and sulfuration treatment. Benefitting from the synergistic effect of the hollow structure and the built-in electric field induced by the heterostructure, the as-prepared Fe2O3/Fe7S8 composite anode exhibits high specific capacity (947 mA h g-1 after 100 cycles at 0.2 A g-1), excellent rate capability, and long-term cycling stability (730 mA h g-1 after 1000 cycles at 1 A g-1).

Recognition of the inducible, secretory small protein OsSSP1 by the membrane receptor OsSSR1 and the co-receptor OsBAK1 confers rice resistance to the blast fungus.

The plant apoplast, which serves as the frontline battleground for long-term host-pathogen interactions, harbors a wealth of disease resistance resources. However, the identification of the disease resistance proteins in the apoplast is relatively lacking. In this study, we identified and characterized the rice secretory protein OsSSP1 (Oryza sativa secretory small protein 1). OsSSP1 can be secreted into the plant apoplast, and either in vitro treatment of recombinant OsSSP1 or overexpression of OsSSP1 in rice could trigger plant immune response. The expression of OsSSP1 is suppressed significantly during Magnaporthe oryzae infection in the susceptible rice variety Taibei 309, and OsSSP1-overexpressing lines all show strong resistance to M. oryzae. Combining the knockout and overexpression results, we found that OsSSP1 positively regulates plant immunity in response to fungal infection. Moreover, the recognition and immune response triggered by OsSSP1 depend on an uncharacterized transmembrane OsSSR1 (secretory small protein receptor 1) and the key co-receptor OsBAK1, since most of the induced immune response and resistance are lost in the absence of OsSSR1 or OsBAK1. Intriguingly, the OsSSP1 protein is relatively stable and can still induce plant resistance after 1 week of storage in the open environment, and exogenous OsSSP1 treatment for a 2-week period did not affect rice yield. Collectively, our study reveals that OsSSP1 can be secreted into the apoplast and percepted by OsSSR1 and OsBAK1 during fungal infection, thereby triggering the immune response to enhance plant resistance to M. oryzae. These findings provide novel resources and potential strategies for crop breeding and disease control.

The time course of category-based attentional template pre-activation depends on the category framework.

When searching for a target defined by a set of objects, attention can be directed toward task-relevant objects by creating a category-based attentional template (CAT). Previous studies have found that CAT can be activated before the onset of the target. However, the time course of CAT pre-activation and whether the category framework (prototypical or semantic) can modulate it remain unclear. To explore the time course of CAT pre-activation, we employed a rapid serial probe presentation paradigm (RSPP) with event-related potentials (ERPs). To investigate the effect of the category framework on the time course of CAT pre-activation, the target category was defined as the prototypical category (Experiment 1) or the semantic category (Experiment 2). The results showed that the prototype-based CAT was pre-activated 300 ms prior to the target, whereas the semantics-based CAT was pre-activated 1500 ms before the onset of the target. The difference in the time course of pre-activation between the two CAT types indicates that the category framework can modulate the time course of CAT pre-activation. Additionally, during the attentional selection phase, an overall comparison of the target revealed that a larger N2pc was elicited by the prototype-based CAT than by the semantics-based CAT, suggesting that the prototype-based CAT could capture more attention than the semantics-based CAT. The findings on the difference between the two CAT frameworks in the preparatory and attentional selection phases provide more evidence for categorical information in visual search and extend our understanding of the mechanism of categorical attentional selection.

Green synthesis of silver nanoparticles using Eucommia ulmoides leaf extract for inhibiting stem end bacteria in cut tree peony flowers.

Tree peony ( Paeonia suffruticosa Andr.) is a popular cut flower among ornamental plants. However, its short vase life severely hinders the production and application of cut tree peony flowers. To extend the postharvest longevity and improve the horticultural value, silver nanoparticles (Ag-NPs) was applied for reducing bacterial proliferation and xylem blockage in cut tree peony flowers in vitro and in vivo. Ag-NPs was synthesized with the leaf extract of Eucommia ulmoides and characterized. The Ag-NPs aqueous solution showed inhibitory activity against bacterial populations isolated from stem ends of cut tree peony 'Luoyang Hong' in vitro. The minimum inhibitory concentration (MIC) was 10 mg L-1. Compared with the control, pretreatments with Ag-NPs aqueous solution at 5 and 10 mg L-1 for 24 h increased flower diameter, relative fresh weight (RFW), and water balance of tree peony 'Luoyang Hong' flowers. Additionally, malondialdehyde (MDA) and H2O2 content in pretreated petals were lower than the control during the vase life. The activities of superoxide dismutase (SOD) and catalase (CAT) in pretreated petals were lower than that of the control at the early vase stage and higher at the late vase life. Furthermore, pretreatments with Ag-NPs aqueous solution at 10 mg L-1 for 24 h could reduce bacterial proliferation in the xylem vessels on the stem ends by confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM). Overall, pretreatments with green synthesized Ag-NPs aqueous solution effectively reduced bacteria-induced xylem blockage of cut tree peony, resulting in improved water uptake, extended vase life, and enhanced postharvest quality. Therefore, this technique can be used as a promising postharvest technology in the cut flower industry.

A 0.99-to-4.38 uJ/class Event-Driven Hybrid Neural Network Processor for Full-Spectrum Neural Signal Analyses.

Versatile and energy-efficient neural signal processors are in high demand in brain-machine interfaces and closed-loop neuromodulation applications. In this paper, we propose an energy-efficient processor for neural signal analyses. The proposed processor utilizes three key techniques to efficiently improve versatility and energy efficiency. 1) Hybrid neural network design: The processor supports artificial neural network (ANN)- and spiking neural network (SNN)-based neuromorphic processing where ANN is used to support the processing of ExG signals and SNN is used for handling neural spike signals. 2) Event-driven processing: The processor can perform always-on binary neural network (BNN)-based event detection with low-energy consumption, and it only switches to the high-accuracy convolutional neural network (CNN)-based recognition mode when events are detected. 3) Reconfigurable architecture: By exploiting the computational similarity of different neural networks, the processor supports critical BNN, CNN, and SNN operations with the same processing elements, achieving significant area reduction and energy efficiency improvement over those of a naive implementation. It achieves 90.05% accuracy and 4.38 uJ/class in a center-out reaching task with an SNN and 99.4% sensitivity, 98.6% specificity, and 1.93 uJ/class in an EEG-based seizure prediction task with dual neural network-based event-driven processing. Moreover, it achieves a classification accuracy of 99.92%, 99.38%, and 86.39% and energy consumption of 1.73, 0.99, and 1.31 uJ/class for EEG-based epileptic seizure detection, ECG-based arrhythmia detection, and EMG-based gesture recognition, respectively.

Geometrically accurate real-time volumetric visualization of the middle ear using optical coherence tomography.

We introduce a novel system for geometrically accurate, continuous, live, volumetric middle ear optical coherence tomography imaging over a 10.9mm×30∘×30∘ field of view (FOV) from a handheld imaging probe. The system employs a discretized spiral scanning (DC-SC) pattern to rapidly collect volumetric data and applies real-time scan conversion and lateral angular distortion correction to reduce geometric inaccuracies to below the system's lateral resolution over 92% of the FOV. We validate the geometric accuracy of the resulting images through comparison with co-registered micro-computed tomography (micro-CT) volumes of a phantom target and a cadaveric middle ear. The system's real-time volumetric imaging capabilities are assessed by imaging the ear of a healthy subject while performing dynamic pressurization of the middle ear in a Valsalva maneuver.