Ubiquitin-mediated degradation of SlPsbS regulates low night temperature tolerance in tomatoes.

PsbS protein is essential for the rapid induction of non-photochemical quenching (NPQ) under low night temperatures (LNTs), but its stability is often affected by adverse environmental conditions. However, the regulatory mechanism for the stability of PsbS or chloroplast proteins remains to be fully characterized. We show that LNT decreases NPQ levels and SlPsbS protein abundance in tomato leaves. LNT-activated chloroplast vesicles (SlCVs) targeting the chloroplasts induce the formation of CV-containing vesicles (CCVs) containing SlPsbS, exported from the chloroplasts. Subsequently, SlCV and SlPsbS contact COP9 signalosome subunit 5A (SlCSN5A) in the cytosol and are ubiquitinated and degraded. Genetic evidence demonstrates that the overexpression of SlCV aggravates SlPsbS protein degradation, whereas silencing of SlCSN5 and SlCV delays LNT-induced NPQ reduction and SlPsbS protein turnover. This study reveals a ubiquitin-dependent degradation pathway of chloroplast proteins co-mediated by CV and CSN5A, thereby providing a basic reference for the regulation of chloroplast protein stability under stress conditions.

The role of apoptosis, immunogenic cell death, and macrophage polarization in carbon ion radiotherapy for keloids: Targeting the TGF-ß1/SMADs signaling pathway.

Keloids, characterized by excessive extracellular matrix (ECM) deposition and aberrant fibrous tissue proliferation, present significant therapeutic challenges due to their recalcitrant and recurrent nature. This study explores the efficacy of Carbon Ion Radiotherapy (CIRT) as a novel therapeutic approach for keloids, focusing on its impact on fibroblast proliferation, apoptosis induction, immunogenic cell death (ICD), macrophage polarization, and the TGF-ß/SMAD signaling pathway. Utilizing a murine model of keloid formed by subcutaneous injection of zeocin in C57BL/6 mice, we demonstrated that CIRT effectively reduces collagenous fiber synthesis and collagen production in keloid tissues. Further, CIRT was shown to inhibit keloid fibroblast proliferation and to induce apoptosis, as evidenced by increased expression of apoptosis-related proteins and confirmed through flow cytometry and TUNEL assay. Notably, CIRT induced mitochondrial stress, leading to enhanced immunogenicity of cell death, characterized by increased expression of ICD markers and secretion of interferon-γ. Additionally, CIRT promoted a shift from M2 to M1 macrophage polarization, potentially reducing TGF-ß release and mitigating ECM deposition. Our findings suggest that CIRT mediates its therapeutic effects through the inhibition of the TGF-ß/SMAD signaling pathway, thereby attenuating ECM formation and offering a promising avenue for keloid treatment. This study underscores the potential of CIRT as an innovative strategy for managing keloids, highlighting its multifaceted impact on key cellular processes involved in keloid pathogenesis.

A comparative assessment of age-related nicotinamide adenine dinucleotide phosphate-diaphorase positivity in the spinal cord and medulla oblongata of pigeons, rats, and mice.

Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (N-d) positive neurons have been extensively studied across various animals, and N-d neurodegenerative neurites have been detected in some aged animal models. However, detailed knowledge on N-d positivity and aging-related alterations in the spinal cord and medulla oblongata of pigeons is limited. In this study, we investigated N-d positivity and age-related changes in the pigeon's spinal cord and medulla oblongata and compared them to those in rats and mice. Pigeons, had more N-d neurons in the dorsal horn, around the central canal, and in the column of Terni in the thoracic and lumbar segments, with scattered neurons found in the ventral horn of the spinal segments. N-d neurons were also present in the white matter of the spinal cord. Morphometric analysis revealed that the size of N-d soma in the lumbosacral, cervical, and thoracic regions was substantially altered in aged pigeons compared to young birds. Furthermore, the lumbar to sacral segments underwent significant morphological alterations. The main findings of this study were the presence of age-related N-d positive bodies (ANB) in aged pigeons, predominantly in the external cuneate nucleus (CuE) and occasionally in the gracilis and CuEs. ANBs were also identified in the gracile nuclei and spinal cord in the aged rats and mice, whereas in aged rats, ANBs were detected in the CuE spinal nucleus. Immunohistochemistry showed that the age-related alterations occurred in the cell types and neuropeptides in old animals. The results suggest weak inflammatory response and neuronal dysfunction in the spinal cord in aged pigeons. Our results suggested that the ANB could be a potential aging marker for the central nervous system.

Chronic ethanol exposure induces cardiac fibroblast transdifferentiation via ceramide accumulation and oxidative stress.

AIMS: Excessive alcohol consumption is associated with cardiac dysfunction and the development of myocardial fibrosis. In this study, we aimed to investigate the direct impacts of ethanol on myocardial fibroblasts and elucidate the underlying mechanism responsible for chronic ethanol-induced myocardial fibrosis. METHODS: Rat primary cardiac fibroblasts exposed to ethanol for 24 h and C57BL/6J mice fed on Lieber-DeCarli diet to establish an ethanol intoxication model in vitro and in vivo, respectively. Histological analyses, molecular biology techniques, and analytical chemistry methods were then conducted. RESULTS AND CONCLUSION: In vivo and vitro experiments revealed that chronic ethanol exposure induced increased myocardial fibrosis and augmented the transdifferentiation of myocardial fibroblasts. Simultaneously, it elicited an upregulation in the production of long-chain and very-long-chain ceramides in cardiac fibroblasts. The excessive accumulation of ceramide leads to elevated levels of intracellular oxidative stress, culminating in the activation of TGF-ß-SMAD3 signaling and the development of fibrosis. Intervention of these pathways with pharmacological inhibitors in vitro or in vivo inhibited fibrosis. In conclusion, ethanol increased ceramides and reactive oxygen species (ROS) in cardiac fibroblasts, resulting in the activation of TGF-ß-SMAD3 signaling, transdifferentiation of fibroblasts, and myocardial fibrosis.

Prediction of Prognosis and Immunotherapy Response of Gastric Cancer Based on Glutamine Metabolism-Related Genes.

BACKGROUND: Reprogramming of glutamine metabolism in Gastric Cancer (GC) can significantly affect the tumor immune microenvironment and immunotherapy. This study examines the role of glutamine metabolism in the microenvironment and prognosis of gastric cancer. METHODS: We obtained gene expression data and clinical information of patients from the TCGA database. The patients were divided into two metabolic subtypes based on consistent clustering. A prognostic risk model containing three glutamine metabolism-related genes (GMRGs) was developed using Lasso-Cox. It was validated by the GEO validation cohort. Additionally, the immune microenvironment composition of the highand low-risk groups was assessed using ESTIMATE, CIBERSORT, and ssGSEA. Drug sensitivity analysis was conducted using the "oncoPredict" R package. RESULTS: We outlined the distinct clinical characteristics of two subtypes and developed a prognostic risk model. The high-risk group has a poorer prognosis due to an increased expression of immune checkpoints and immunosuppressive cellular infiltration. Our analysis, which included Cox risk regression, ROC curves, and nomogram, demonstrated that this risk model is an independent prognostic factor. The TIDE score was higher in the high-risk group than in the low-risk group. Additionally, the high-risk group did not respond well to chemotherapeutic drug treatment. CONCLUSION: This study shows that modelling glutamine metabolism is a good predictor of prognosis and immunotherapy efficacy in gastric cancer. Thus, we can better understand the role of glutamine metabolism in the development of cancer and use these insights to develop more targeted and effective treatments.

Type 2 herpes simplex virus-induced anti-N-methyl-D-aspartate receptor encephalitis responsive to immunoglobulin monotherapy.

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.

XPO1 serves as a prognostic marker involving AKT/MAPK/TGFBR1 pathway in OSCC.

BACKGROUND: Exportin 1 (XPO1) is a nuclear export protein that facilitates the transportation of various substances. XPO1 promotes tumor development as a poor prognostic factor in a variety of tumors and is a therapeutic target for screening inhibitors. However, the role of XPO1 in oral squamous cell carcinoma (OSCC) has yet to be determined. METHODS: The expression patterns of XPO1 mRNA in OSCC were investigated using bioinformatics tools, and the expression levels of XPO1 protein in OSCC specimens were confirmed by immunohistochemical assays. Survival analysis was conducted to evaluate the impact of XPO1 on prognosis. GO and KEGG enrichment analyses were utilized to uncover the signaling pathways mediated by XPO1. Additionally, we examined the association between XPO1 and AKT/MAPK/TGFBR1 and immune infiltration. RESULTS: XPO1 mRNA and protein expression levels were significantly enhanced in OSCC and associated with OSCC severity. Enhanced XPO1 expression was indicative of poor survival. Functional analysis showed that XPO1 mediated pathways associated with cell cycle and DNA replication and reduced immune infiltration in OSCC. Additionally, XPO1 mRNA and protein expression levels had significant positive relationships with AKT/MAPK/TGFBR1. CONCLUSIONS: XPO1, as a marker of poor prognosis in OSCC, can promote OSCC through AKT/MAPK/TGFBR1.

Causal relationship of inflammatory cytokines and serum metabolites in cerebral small vessel disease: a two-step Mendelian randomization study.

BACKGROUND AND PURPOSE: The aim was to investigate the causal relationships of inflammatory cytokines and serum metabolites in cerebral small vessel disease (CSVD). METHODS: Bidirectional Mendelian randomization was first conducted to screen inflammatory cytokines and serum metabolites that were associated with imaging features of CSVD, including white matter hyperintensities, recent small subcortical infarcts, cortical cerebral microinfarcts, cerebral microbleeds, lacunes and enlarged perivascular spaces. Sensitivity analyses were performed to evaluate the robustness and pleiotropy of these results. Subsequently, inflammatory cytokines and serum metabolites that were associated with CSVD were subjected to functional enrichment. Finally, mediation analysis was employed to investigate whether inflammatory cytokines or serum metabolites acted as an intermediary for the other in their causal relationship with CSVD. RESULTS: Of the inflammatory cytokines, five were risk factors (e.g., tumour-necrosis-factor-related apoptosis-inducing ligand) and five (e.g., fibroblast growth factor 19) were protective factors for CSVD. Eleven serum metabolites that increased CSVD risk and 13 metabolites that decreased CSVD risk were also identified. The majority of these markers of CSVD susceptibility were lipid metabolites. Natural killer cell receptor sub-type 2B4 was determined to act as a mediating factor of an unidentified metabolite for the enlargement of perivascular spaces. CONCLUSION: Several inflammatory cytokines and serum metabolites had causal relationships with imaging features of CSVD. A natural killer cell receptor mediated in part the promotional effect of a metabolite on perivascular space enlargement.

Myeloid Cells and Sensory Nerves Mediate Peritendinous Adhesion Formation via Prostaglandin E2.

Peritendinous adhesion that forms after tendon injury substantially limits daily life. The pathology of adhesion involves inflammation and the associated proliferation. However, the current studies on this condition are lacking, previous studies reveal that cyclooxygenase-2 (COX2) gene inhibitors have anti-adhesion effects through reducing prostaglandin E2 (PGE2) and the proliferation of fibroblasts, are contrary to the failure in anti-adhesion through deletion of EP4 (prostaglandin E receptor 4) gene in fibroblasts in mice of another study. In this study, single-cell RNA sequencing analysis of human and mouse specimens are combined with eight types of conditional knockout mice and further reveal that deletion of COX2 in myeloid cells and deletion of EP4 gene in sensory nerves decrease adhesion and impair the biomechanical properties of repaired tendons. Furthermore, the COX2 inhibitor parecoxib reduces PGE2 but impairs the biomechanical properties of repaired tendons. Interestingly, PGE2 local treatment improves the biomechanical properties of the repaired tendons. These findings clarify the complex role of PGE2 in peritendinous adhesion formation (PAF) and tendon repair.

Effects of Hypertension on Alzheimer's Disease: Updates in Pathophysiological and Neuroimaging Findings.

Alzheimer's disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.

Identification of Isoliensinine as a Ferroptosis Suppressor with Iron-Chelating Activity.

Ferroptosis is a type of regulated cell death driven by the iron-dependent accumulation of lipid peroxides. The high involvement of ferroptosis in diverse human diseases highlights the need for the identification of new chemotypes with anti-ferroptotic activity. Here, we performed a natural product library screening in HT1080 fibrosarcoma cells and identified licochalcone A (LA), isoeugenyl acetate (ISA), and isoliensinine (ISL) as suppressors of either RSL3- or IKE-induced ferroptosis. Mechanistically, ferroptosis resistance conferred by these compounds is mainly through GPX4/NRF2-independent mechanisms. Among them, only ISL could effectively rescue ferroptosis induced by FINO2, which is a stable oxidant of ferrous iron, suggesting that ISL may have the properties of an iron chelator. Consistent with the hypothesis, both computational tools and X-ray photoelectron spectroscopy supported the binding between ISL and iron ions. And ISL greatly inhibited excessive iron-dependent ferroptotic cell death through limiting intracellular iron accumulation. Furthermore, its iron chelator activity also protected mice from organ injury in an acute iron overload model. In conclusion, this study provided valuable insights for developing effective anti-ferroptosis agents from natural products, which represent a potential therapeutic strategy for treating ferroptosis-associated organ damage.

Comparative transcriptome analysis and HPLC reveal candidate genes associated with synthesis of bioactive constituents in Rheum palmatum complex.

Content of bioactive constituents is one of the most important characteristics in Rheum palmatum complex. Increasing ingredient content through genetic breeding is an effective strategy to solve the contradiction between large market demand and resource depletion, but currently hampered by limited understanding of metabolite biosynthesis in rhubarb. In this study, deep transcriptome sequencing was performed to compare roots, stems, and leaves of two Rheum species (PL and ZK) that show different levels of anthraquinone contents. Approximately 0.52 billion clean reads were assembled into 58,782 unigenes, of which around 80% (46,550) were found to be functionally annotated in public databases. Expression patterns of differential unigenes between PL and ZK were thoroughly investigated in different tissues. This led to the identification of various differentially expressed genes (DEGs) involved in shikimate, MEP, MVA, and polyketide pathways, as well as those involved in catechin and gallic acid biosynthesis. Some structural enzyme genes were shown to be significantly up-regulated in roots of ZK with high anthraquinone content, implying potential central roles in anthraquinone synthesis. Taken together, our study provides insights for future functional studies to unravel the mechanisms underlying metabolite biosynthesis in rhubarb. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01492-z.

Protein blend extrusion: Crafting meat analogues with varied textural structures and characteristics.

With an increasing emphasis on health and environmental consciousness, there is a growing inclination toward plant protein-based meat substitutes as viable alternatives to animal meat. In the pursuit of creating diverse and functional plant protein-based substitutes, innovative plant proteins have been introduced in conjunction with soy protein isolate (SPI), encompassing pea protein isolate (PPI), rice bran protein (RBP), fava bean protein isolate (FPI), and spirulina protein isolate (SPPI). Notably, SPI-WG extrudates and SPI-PPI extrudates exhibited superior fiber structures (fiber degrees were 1.72 and 1.88, respectively), with coarse fibers in SPI-WG extrudates and fine, dense fibers in SPI-PPI extrudates. The addition of RBP, FPI and SPPI had minimal effect on fiber structure. Fresh SPI-FPI displayed the slowest rate of water loss, losing about 7.11% of their total weight in 5 h. Different plant proteins can be selected for the preparation of plant protein-based meat substitutes according to practical needs.

Transferable Optical Enhancement Nanostructures by Gapless Stencil Lithography.

Optical spectroscopy techniques are central for the characterization of two-dimensional (2D) quantum materials. However, the reduced volume of atomically thin samples often results in a cross section that is far too low for conventional optical methods to produce measurable signals. In this work, we developed a scheme based on the stencil lithography technique to fabricate transferable optical enhancement nanostructures for Raman and photoluminescence spectroscopy. Equipped with this new nanofabrication technique, we designed and fabricated plasmonic nanostructures to tailor the interaction of few-layer materials with light. We demonstrate orders-of-magnitude increase in the Raman intensity of ultrathin flakes of 2D semiconductors and magnets as well as selective Purcell enhancement of quenched excitons in WSe2/MoS2 heterostructures. We provide evidence that the method is particularly effective for air-sensitive materials, as the transfer can be performed in situ. The fabrication technique can be generalized to enable a high degree of flexibility for functional photonic devices.

N-level complex helical structure modeling method.

This paper primarily explores the modeling method of n-level complex helical structures with coal mining machine cables as the research object. The paper first elaborately introduces the modeling method of n-level helix curves based on parametric equations and coordinate transformations, and compensates for the n-level helix curves with corrected pitch, which can obtain more accurate n-level helix curves and improve the accuracy of n-level helix curves modeling. Subsequently, based on this high-precision n-level helix curves modeling method, the paper elaborates on the method of solving pitch and twisting radius of multi-layer helical structure. Calculation scripts were written based on the above methods, which can be used to batch calculate the twisting radius and pitch of each layer structure in multi-layer structures when satisfying the conditions of in-layer tangency, inter-layer tangency, and extrusion deformation, and retain the actual results through logical judgment. Then, based on the above two methods, the paper developed a modeling method for braided structures based on piecewise functions containing fifth-order polynomials, which can effectively avoid the problem of insufficiently dense arrangement of braided lines and easy interference in traditional methods. Finally, a set of modeling tools was developed using C# and Python in Grasshopper to implement the modeling algorithm. Taking the MCPT-1.9/3.3 3120 + 170 + 4 * 10 coal mining machine cable as an example. The cable was modeled using both the method proposed in this paper and the traditional method. Comparative data shows that the method proposed in this paper can reduce errors by 3.31E6 times in the second-level and above helical structures. In addition this paper compares the standard line length, measured line length, and the line length established by the proposed model, showing that the relative errors are both less than 0.1941%. This paper provides a new, systematic, high-precision, and full-process cable modeling method, in which all parameters except the process parameters are accurately solved by equations. It lays a theoretical foundation for the high-precision simulation and intelligent sensing cables, which is of great significance for improving the safety, stability, and efficient development of the coal mining industry. The research results of the paper can not only be applied to the modeling of coal mining machine cables but also can be extended to the modeling of other complex multi-layer helical structures.

Light-driven C-H activation mediated by 2D transition metal dichalcogenides.

C-H bond activation enables the facile synthesis of new chemicals. While C-H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C-H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C-C coupling mediated by 2D TMDCs to promote C-H activation and carbon dots synthesis. Our results shed light on 2D materials for C-H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.

PST-Diff: Achieving High-consistency Stain Transfer by Diffusion Models with Pathological and Structural Constraints.

Histopathological examinations heavily rely on hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining. IHC staining can offer more accurate diagnostic details but it brings significant financial and time costs. Furthermore, either re-staining HE-stained slides or using adjacent slides for IHC may compromise the accuracy of pathological diagnosis due to information loss. To address these challenges, we develop PST-Diff, a method for generating virtual IHC images from HE images based on diffusion models, which allows pathologists to simultaneously view multiple staining results from the same tissue slide. To maintain the pathological consistency of the stain transfer, we propose the asymmetric attention mechanism (AAM) and latent transfer (LT) module in PST-Diff. Specifically, the AAM can retain more local pathological information of the source domain images through the design of asymmetric attention mechanisms, while ensuring the model's flexibility in generating virtual stained images that highly confirm to the target domain. Subsequently, the LT module transfers the implicit representations across different domains, effectively alleviating the bias introduced by direct connection and further enhancing the pathological consistency of PST-Diff. Furthermore, to maintain the structural consistency of the stain transfer, the conditional frequency guidance (CFG) module is proposed to precisely control image generation and preserve structural details according to the frequency recovery process. To conclude, the pathological and structural consistency constraints provide PST-Diff with effectiveness and superior generalization in generating stable and functionally pathological IHC images with the best evaluation score. In general, PST-Diff offers prospective application in clinical virtual staining and pathological image analysis.

Boosting Monolayer Transition Metal Dichalcogenides Growth by Hydrogen-Free Ramping during Chemical Vapor Deposition.

The controlled vapor-phase synthesis of two-dimensional (2D) transition metal dichalcogenides (TMDs) is essential for functional applications. While chemical vapor deposition (CVD) techniques have been successful for transition metal sulfides, extending these methods to selenides and tellurides often faces challenges due to uncertain roles of hydrogen (H2) in their synthesis. Using CVD growth of MoSe2 as an example, this study illustrates the role of a H2-free environment during temperature ramping in suppressing the reduction of MoO3, which promotes effective vaporization and selenization of the Mo precursor to form MoSe2 monolayers with excellent crystal quality. As-synthesized MoSe2 monolayer-based field-effect transistors show excellent carrier mobility of up to 20.9 cm2/(V·s) with an on-off ratio of 7 × 107. This approach can be extended to other TMDs, such as WSe2, MoTe2, and MoSe2/WSe2 in-plane heterostructures. Our work provides a rational and facile approach to reproducibly synthesize high-quality TMD monolayers, facilitating their translation from laboratory to manufacturing.

A Review of Diamond Materials and Applications in Power Semiconductor Devices.

Diamond is known as the ultimate semiconductor material for electric devices with excellent properties such as an ultra-wide bandgap (5.47 eV), high carrier mobility (electron mobility 4000 cm2/V·s, hole mobility 3800 cm2/V·s), high critical breakdown electric field (20 MV/cm), and high thermal conductivity (22 W/cm·K), showing good prospects in high-power applications. The lack of n-type diamonds limits the development of bipolar devices; most of the research focuses on p-type Schottky barrier diodes (SBDs) and unipolar field-effect transistors (FETs) based on terminal technology. In recent years, breakthroughs have been made through the introduction of new structures, dielectric materials, heterogeneous epitaxy, etc. Currently, diamond devices have shown promising applications in high-power applications, with a BV of 10 kV, a BFOM of 874.6 MW/cm2, and a current density of 60 kA/cm2 already realized. This review summarizes the research progress of diamond materials, devices, and specific applications, with a particular focus on the development of SBDs and FETs and their use in high-power applications, aiming to provide researchers with the relevant intuitive parametric comparisons. Finally, the paper provides an outlook on the parameters and development directions of diamond power devices.