The roles of nuclear orphan receptor NR2F6 in anti-viral innate immunity.

Proper transcription regulation by key transcription factors, such as IRF3, is critical for anti-viral defense. Dynamics of enhancer activity play important roles in many biological processes, and epigenomic analysis is used to determine the involved enhancers and transcription factors. To determine new transcription factors in anti-DNA-virus response, we have performed H3K27ac ChIP-Seq and identified three transcription factors, NR2F6, MEF2D and MAFF, in promoting HSV-1 replication. NR2F6 promotes HSV-1 replication and gene expression in vitro and in vivo, but not dependent on cGAS/STING pathway. NR2F6 binds to the promoter of MAP3K5 and activates AP-1/c-Jun pathway, which is critical for DNA virus replication. On the other hand, NR2F6 is transcriptionally repressed by c-Jun and forms a negative feedback loop. Meanwhile, cGAS/STING innate immunity signaling represses NR2F6 through STAT3. Taken together, we have identified new transcription factors and revealed the underlying mechanisms involved in the network between DNA viruses and host cells.

Identifying high-order plasmon modes in silver nanoparticle-over-mirror configuration.

Metallic nanoparticle-over-mirror (NPOM) represents as a versatile plasmonic configuration for surface enhanced spectroscopy, sensing and light-emitting metasurfaces. However, experimentally identifying the high-order localized surface plasmon modes in NPOM, especially for the best plasmonic material silver, is often hindered by the small scattering cross-section of high-order plasmon modes and the poor reproducibility of the spectra across different NPOMs, resulted from the polyhedral morphology of the colloidal nanoparticles or the rough surface of deposited polycrystalline metals. In this study, we identify the high-order localized surface plasmon modes in silver NPOM by using differential reflection spectroscopy. We achieved reproducible single-particle absorption spectra by constructing uniform NPOM consisting of silver nanospheres, single-crystallized silver microplates, and a self-assembled monolayer of 1,10-decanedithiol. For comparison, silver NPOM created from typical polycrystalline films exhibits significant spectral fluctuations, even when employing template stripping methods to minimize the film roughness. Identifying high-order plasmon modes in the NPOM configuration offers a pathway to construct high-quality plasmonic substrates for applications such as colloidal metasurface, surface-enhanced Raman spectroscopy, fluorescence, or infrared absorption.

Compact auto-aligning interferometers with picometer precision.

This research introduces a compact, auto-aligning interferometer engineered for measuring translations with a wide angular working range and picometer precision above 1H z. It presents a design ensuring automatic beam alignment during movement through secondary reflection from a corner reflector. The sensor head, a 20×10×10m m 3 all-glass quasi-monolithic structure, exhibits a displacement sensitivity below 1p m/H z 1/2 above 1H z and a wide angular working range of ±200m r a d. This versatile optical design holds promise to improve the sensitivity in applications such as laser ranging, optical seismometers, precision manufacturing, and metrology.

Automated identification of pesticide mixtures via machine learning analysis of TLC-SERS spectra.

Identification of components in pesticide mixtures has been a major challenge in spectral analysis. In this paper, we assembled monolayer Ag nanoparticles on Thin-layer chromatography (TLC) plates to prepare TLC-Ag substrates with mixture separation and surface-enhanced Raman scattering (SERS) detection. Spectral scans were performed along the longitudinal direction of the TLC-Ag substrate to generate SERS spectra of all target analytes on the TLC plate. Convolutional neural network classification and spectral angle similarity machine learning algorithms were used to identify pesticide information from the TLC-SERS spectra. It was shown that the proposed automated spectral analysis method successfully classified five categories, including four pesticides (thiram, triadimefon, benzimidazole, thiamethoxam) as well as a blank TLC-Ag data control. The location of each pesticide on the TLC plate was determined by the intersection of the information curves of the two algorithms with 100 % accuracy. Therefore, this method is expected to help regulators understand the residues of mixed pesticides in agricultural products and reduce the potential risk of agricultural products to human health and the environment.

Heparin-Binding Protein Promotes Acute Lung Injury in Sepsis Mice by Blocking the Aryl Hydrocarbon Receptor Signaling Pathway.

Purpose: This study aimed to explore the therapeutic effect and potential mechanism of heparin-binding protein (HBP) reduction on sepsis-related acute lung injury. Methods: We utilized a murine model of sepsis-induced by intraperitoneal injection of lipopolysaccharides (LPS) in C57BL/6J mice divided into four groups: Control, LPS, Anti-HBP, and ceftriaxone (CEF). Following sepsis induction, Anti-HBP or CEF treatments were administered, and survival rates were monitored for 48 h. We then used reverse-transcription quantitative PCR to analyze the expression levels of HBP in lung tissues, immunohistochemistry for protein localization, and Western blotting for protein quantification. Pulmonary inflammation was assessed using enzyme-linked immunosorbent assays of proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, and interferon-γ). The activation state of the aryl hydrocarbon receptor (AhR) signaling pathway was determined via Western blotting, evaluating both cytoplasmic and nuclear localization of AhR and the expression of cytochrome P450 1A1 protein by its target gene. Results: Anti-HBP specifically reduced HBP levels. The survival rate of mice in the Anti-HBP and CEF groups was much higher than that in the LPS group. The severity of lung injury and pulmonary inflammatory response in the Anti-HBP and CEF groups was significantly lower than that in the LPS group. AhR signaling pathway activation was observed in the Anti-HBP and CEF groups. Additionally, there was no significant difference in the above indices between the Anti-HBP and CEF groups. Conclusion: HBP downregulation in lung tissues significantly improved LPS-induced lung injury and the pulmonary inflammatory response, thereby prolonging the survival of sepsis mice, suggesting activation of the AhR signaling pathway. Moreover, the effect of lowering the HBP level was equivalent to that of the classical antibiotic CEF. Trial Registration: Not applicable.

CD8+ tissue-resident memory T cells are expanded in primary Sjögren's disease and can be therapeutically targeted by CD103 blockade.

OBJECTIVE: Tissue-resident memory cells (Trm) are a subset of T cells residing persistently and long-term within specific tissues that contribute to persistent inflammation and tissue damage. We characterised the phenotype and function of Trm and the role of CD103 in primary Sjogren's syndrome (pSS). METHODS: In both pSS and non-pSS sicca syndrome patients, we examined Trm frequency, cytokine production in salivary glands (SG) and peripheral blood (PB). We also analysed Trm-related gene expression in SG biopsies through bulk and single-cell RNA sequencing (scRNAseq). Additionally, we investigated Trm properties in an immunisation-induced animal model of pSS (experimental SS, ESS) mouse model and assessed the effects of Trm inhibition via intraglandular anti-CD103 monoclonal antibody administration. RESULTS: Transcriptomic pSS SG showed an upregulation of genes associated with tissue recruitment and long-term survival of Trm cells, confirmed by a higher frequency of CD8+CD103+CD69+ cells in pSS SG, compared with non-specific sialadenitis (nSS). In SG, CD8+ CD103+ Trm contributed to the secretion of granzyme-B and interferon-γ, CD8+ Trm cells were localised within inflammatory infiltrates, where PD1+CD8+ T cells were also increased compared with nSS and MALT lymphoma. scRNAseq of PB and pSS SG T cells confirmed expression of CD69, ITGAE, GZMB, GZMK and HLA-DRB1 among CD3+CD8+ SG T cells. In the SG of ESS, CD8+CD69+CD103+ Trm producing Granzyme B progressively expanded. However, intraglandular blockade of CD103 in ESS reduced Trm, reduced glandular damage and improved salivary flow. CONCLUSIONS: CD103+CD8+Trm cells are expanded in the SG of pSS and ESS, participate in tissue inflammation and can be therapeutically targeted.

Causal relationship between inflammatory proteins and glioblastoma: a two-sample bi­directional mendelian randomization study.

Background: Observational studies have indicated a potential correlation between glioblastoma and circulating inflammatory proteins. Further investigation is required to establish a causal relationship between these two factors. Methods: We performed a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary of 91 circulating inflammation-related proteins (N = 14,824) to assess their causal impact on glioblastoma. The GWAS summary data for glioblastoma included 243 cases and 287,137 controls. The inverse variance weighted (IVW) method was used as the primary analytical method to assess causality. Four additional MR methods [simple mode, MR-Egger, weighted median, and weighted mode] were used to supplement the IVW results. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Reverse MR analysis was also performed. glioblastoma transcriptomic data from The Cancer Genome Atlas (TCGA) were analyzed to validate the findings obtained through MR, while pathway and functional enrichment analyses were conducted to predict the potential underlying mechanisms. Results: Our findings from employing the inverse variance weighted method in our forward MR analysis provide robust evidence supporting a potential association between glioblastoma and elevated levels of Cystatin D, as well as decreased levels of fibroblast growth factor 21 (FGF21) in the circulation. Moreover, our reverse MR analysis revealed that glioblastoma may contribute to increased concentrations of C-X-C motif chemokine 9 (CXCL9) and Interleukin-33 (IL-33) in the bloodstream. Transcriptomic analysis showed that FGF21 expression was inversely associated with the risk of developing glioblastoma, whereas an increased risk was linked to elevated levels of CXCL9 and IL-33. Pathway and functional enrichment analyses suggested that Cystatin D might exert its effects on glioblastoma through intracellular protein transport, whereas FGF21 might affect glioblastoma via glucose response mechanisms. Conclusion: These results indicate that FGF21 is a significant factor in glioblastoma susceptibility. Glioblastoma also affects the expression of inflammatory proteins such as C-X-C motif chemokine 9 and Interleukin-33, providing new insights into the mechanisms of glioblastoma genesis and clinical research.

Dependency-aware deep generative models for multitasking analysis of spatial omics data.

Spatially resolved transcriptomics (SRT) technologies have significantly advanced biomedical research, but their data analysis remains challenging due to the discrete nature of the data and the high levels of noise, compounded by complex spatial dependencies. Here, we propose spaVAE, a dependency-aware, deep generative spatial variational autoencoder model that probabilistically characterizes count data while capturing spatial correlations. spaVAE introduces a hybrid embedding combining a Gaussian process prior with a Gaussian prior to explicitly capture spatial correlations among spots. It then optimizes the parameters of deep neural networks to approximate the distributions underlying the SRT data. With the approximated distributions, spaVAE can contribute to several analytical tasks that are essential for SRT data analysis, including dimensionality reduction, visualization, clustering, batch integration, denoising, differential expression, spatial interpolation, resolution enhancement and identification of spatially variable genes. Moreover, we have extended spaVAE to spaPeakVAE and spaMultiVAE to characterize spatial ATAC-seq (assay for transposase-accessible chromatin using sequencing) data and spatial multi-omics data, respectively.

Phosphorus and nitrogen supramolecule for fabricating flame-retardant, transparent and robust polyvinyl alcohol film.

Supramolecular flame retardants have attracted increasing attention recently due to their simple and eco-friendly preparation process. In this study, a novel flame retardant HEPFR was prepared using supramolecular self-assembly technology between piperazine and 1-hydroxy ethylidene-1,1-diphosphonic acid (HEDP). It was introduced into polyvinyl alcohol (PVA) matrix to form PVA/HEPFR composite film. Subsequently, the transparency, mechanical properties, thermal stability, and flame retardancy of PVA/HEPFR films were studied. Due to the hydrogen bonded cross-linked network structure between PVA and HEPFR, the mechanical properties of PVA/HEPFR films have been improved, while maintaining good transparency. With 10 wt% addition of HEPFR, PVA films can reach the VTM-0 level in UL-94 testing. And the limiting oxygen index can be increased from 18.5% of pure PVA to 26.5%. The peak heat release rate was reduced by 61.5%. The flame retardancy and thermal stability of PVA/HEPFR films have been greatly improved. This study provides a "one stone, three birds" strategy for preparing flame-retardant, transparent, and robust PVA film.

ScRNA-seq reveals novel immune-suppressive T cells and investigates CMV-TCR-T cells cytotoxicity against GBM.

BACKGROUND: Glioblastoma (GBM) is a fatal primary brain malignancy in adults. Previous studies have shown that cytomegalovirus (CMV) is a risk factor for tumorigenesis and aggressiveness for glioblastoma. However, little is known about how CMV infection affects immune cells in the tumor microenvironment of GBM. Furthermore, there has been almost no engineered T-cell receptor (TCR)-T targeting CMV for GBM research to date. METHODS: We evaluated the CMV infection status of patients with GBM's tumor tissue by immune electron microscopy, immunofluorescence, and droplet digital PCR. We performed single-cell RNA sequencing for CMV-infected GBM to investigate the effects of CMV on the GBM immune microenvironment. CellChat was applied to analyze the interaction between cells in the GBM tumor microenvironment. Additionally, we conducted single-cell TCR/B cell receptor (BCR) sequencing and Grouping of Lymphocyte Interactions with Paratope Hotspots 2 algorithms to acquire specific CMV-TCR sequences. Genetic engineering was used to introduce CMV-TCR into primary T cells derived from patients with CMV-infected GBM. Flow cytometry was used to measure the proportion and cytotoxicity status of T cells in vitro. RESULTS: We identified two novel immune cell subpopulations in CMV-infected GBM, which were bipositive CD68+SOX2+ tumor-associated macrophages and FXYD6+ T cells. We highlighted that the interaction between bipositive TAMs or cancer cells and T cells was predominantly focused on FXYD6+ T cells rather than regulatory T cells (Tregs), whereas, FXYD6+ T cells were further identified as a group of novel immunosuppressive T cells. CMV-TCR-T cells showed significant therapeutic effects on the human-derived orthotopic GBM mice model. CONCLUSIONS: These findings provided an insight into the underlying mechanism of CMV infection promoting the GBM immunosuppression, and provided a novel potential immunotherapy strategy for patients with GBM.

Substrate-Independent Superhydrophobic Coating Capable of Photothermal-Induced Repairability for Multiple Damages Fabricated via Simple Blade Coating.

Repairable superhydrophobic surfaces have promising application potential in many fields. However, so far, it is still a challenge to develop a superhydrophobic surface with repairability for multiple types of damage through a simple method. In this paper, a repairable superhydrophobic coating was obtained on various substrates by blade-coating mixtures of polydimethylsiloxane (PDMS), polyvinylidene fluoride (PVDF), and multiwalled carbon nanotubes (MWCNTs) modified with dopamine (PDA) and octadecylamine (ODA). The obtained coating has a good liquid-repellent property with a water contact angle above 150° and a water sliding angle of ∼6° and possesses an excellent absorbance (∼97%) in the wavelength range of 250-2500 nm. Due to its high absorbance, the coating displays an outstanding photothermal effect with a temperature rise of ∼65 °C under irradiation by 1.0 kW/m2 of simulated sunlight. Furthermore, after being degraded by multiple stimuli, including plasma treatment, acid/alkali/oil immersion, sand impact, and the icing-thawing cycle, the coating can recover superhydrophobicity via sunlight irradiation, demonstrating the good photothermal-induced repairability of the coating. It can be expected that the good water-repellent property, photothermal effect, and repairability give this coating a promising prospect in practical applications.

Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial.

AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.

Analysis of Factors and T-Lymphocyte Subset Changes in Pediatric Recurrent Respiratory Infections Post-Pidotimod Treatment.

Objective: This study aims to analyze factors contributing to recurrent respiratory tract infections (RRTIs) in pediatric patients and evaluate the efficacy of pidotimod (PI) treatment. Methods: This study utilized a retrospective cohort design, enrolling a total of 85 children diagnosed with RRTIs between September 2020 and September 2022, alongside 54 healthy children. Logistic regression analysis was employed to identify factors contributing to RRTI occurrence. Among the participants, 40 children underwent conventional treatment (control group), while 45 received PI treatment (research group). Comparative analyses were conducted to assess clinical efficacy and adverse effects between the two treatment groups. Results: The history of family members' smoking and parental allergy emerged as independent risk factors for RRTIs (P < .05, OR>1), whereas parental education level, outdoor activity, and micronutrient intake were identified as independent protective factors for RRTIs (P < .05, OR<1). Symptoms such as cough, fever, rhonchi, moist rales, and tonsillar enlargement resolved significantly faster in the research group compared to the control group (P < .05). Additionally, the research group exhibited reduced infection duration and fewer recurrent infections (P < .05). Following treatment, the overall treatment efficacy was superior in the research group compared to the control group (P < .05), with no significant difference in the incidence of adverse effects (P > .05). Post-treatment, levels of CD3+, CD4+, and CD4+/CD8+ were elevated in the research group compared to the control group, while CD8+ levels were lower (P < .05). Conclusions: Daily outdoor activity among children, family members' history of smoking, parental allergy history, education level, and micronutrient intake emerged as independent factors influencing pediatric RRTIs. Furthermore, PI was identified as a significant treatment option for RRTIs.

Engineered Microorganisms for Advancing Tumor Therapy.

Engineered microorganisms have attracted significant interest as a unique therapeutic platform in tumor treatment. Compared with conventional cancer treatment strategies, engineering microorganism-based systems provide various distinct advantages, such as the intrinsic capability in targeting tumors, their inherent immunogenicity, in situ production of antitumor agents, and multiple synergistic functions to fight against tumors. Herein, the design, preparation, and application of the engineered microorganisms for advanced tumor therapy are thoroughly reviewed. This review presents a comprehensive survey of innovative tumor therapeutic strategies based on a series of representative engineered microorganisms, including bacteria, viruses, microalgae, and fungi. Specifically, it offers extensive analyses of the design principles, engineering strategies, and tumor therapeutic mechanisms, as well as the advantages and limitations of different engineered microorganism-based systems. Finally, the current challenges and future research prospects in this field, which can inspire new ideas for the design of creative tumor therapy paradigms utilizing engineered microorganisms and facilitate their clinical applications, are discussed.

Millimeter-scale magnetic implants paired with a fully integrated wearable device for wireless biophysical and biochemical sensing.

Implantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors mainly requires transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces biocompatibility, or limits portability. Here, we develop a set of millimeter-scale, chip-less, and battery-less magnetic implants paired with a fully integrated wearable device for measuring biophysical and biochemical signals. The wearable device can induce a large amplitude damped vibration of the magnetic implants and capture their subsequent motions wirelessly. These motions reflect the biophysical conditions surrounding the implants and the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities of measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure, and CSF glucose levels. This miniaturized system opens the possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.

Examination of Oral Candida Infection in Primary Sjögren's Syndrome Patients

Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by symptoms such as dry mouth, dry eyes, and other systematic symptoms. Due to the hyposalivation experienced by pSS patients, oral dysbacteriosis often occurs. A common complication of pSS is the oral Candida infection. In this article, the authors describe systematic methods that can effectively diagnose oral Candida infection and identify the Candida strains using saliva, oral mucosal swabs, or mouthwash from pSS patients. The Sabouraud's Dextrose Agar (SDA), hyphal formation assay, potassium hydroxide (KOH) smear test, and calcofluor white (CFW) staining assay are used for the diagnosis of oral Candida infection. A Candida diagnostic agar is used for the identification of Candida strains. Finally, antifungal susceptibility testing is used to determine appropriate antifungal drug treatment. This standardized method can enhance the diagnosis, treatment, and future research of pSS-related oral Candida infections. Early diagnosis, using this method, can also prevent any complications arising due to delay in receiving appropriate treatment.

Nature-Inspired Molecular-Crowding Enabling Wide-Humidity Range Applicable, Anti-Freezing, and Robust Zwitterionic Hydrogels for On-Skin Electronics.

Hydrogels are currently in the limelight for applications in soft electronics but they suffer from the tendency to lose water or freeze when exposed to dry environments or low temperatures. Molecular crowding is a prevalent occurrence in living cells, in which molecular crowding agents modify the hydrogen bonding structure, causing a significant reduction in water activity. Here, a wide-humidity range applicable, anti-freezing, and robust hydrogel is developed through the incorporation of natural amino acid proline (Pro) and conductive MXene into polyvinyl alcohol (PVA) hydrogel networks. Theoretical calculations reveal that Pro can transform "free water" into "locked water" via the molecular-crowding effect, thereby suppressing water evaporation and ice forming. Accordingly, the prepared hydrogel exhibits high water retention capability, with 77% and 55% being preserved after exposure to 20 °C, 28% relative humidity (RH) and 35 °C, 90% RH for 12 h. Meanwhile, Pro lowers the freezing temperature of the hydrogel to 34 °C and enhances its stretchability and strength. Finally, the PVA/Pro/MXene hydrogels are assembled as multifunctional on-skin strain sensors and conductive electrodes to monitor human motions and detect tiny electrophysiological signals. Collectively, this work provides a molecular crowding strategy that will motivate researchers to develop more advanced hydrogels for versatile applications.

The involvement of RNA N6-methyladenosine and histone methylation modification in decidualization and endometriosis-associated infertility.

Defective decidualization of endometrial stromal cells (ESCs) in endometriosis (EM) patients leads to inadequate endometrial receptivity and EM-associated infertility. Hypoxia is an inevitable pathological process of EM and participates in deficient decidualization of the eutopic secretory endometrium. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses H3K27Me3, leading to decreased expression levels of target genes. Although EZH2 expression is low under normal decidualization, it is abundantly increased in the eutopic secretory endometrium of EM and is induced by hypoxia. Chromatin immunoprecipitation-PCR results revealed that decidua marker IGFBP1 is a direct target of EZH2, partially explaining the increased levels of histone methylation modification in defected decidualization of EM. To mechanism controlling this, we examined the effects of hypoxia on EZH2 and decidualization. EZH2 mRNA showed decreased m6 A modification and increased expression levels under hypoxia and decidualization combined treatment. Increased EZH2 expression was due to the increased expression of m6 A demethylase ALKBH5 and decreased expression of the m6 A reader protein YTHDF2. YTHDF2 directly bind to the m6 A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Moreover, selective Ezh2 depletion in mouse ESCs increased endometrial receptivity and improved mouse fertility by up-regulating decidua marker IGFBP1 expression. This is the first report showing that YTHDF2 can act as a m6 A reader to promote decidualization by decreasing the stability of EZH2 mRNA and further increasing the expression of IGFBP1 in ESCs. Taken together, our findings highlight the critical role of EZH2/H3K27Me3 in decidualization and reveal a novel epigenetic mechanism by which hypoxia can suppress EM decidualization by decreasing the m6 A modification of EZH2 mRNA.

Cathepsin B degrades RbcL during freezing-induced programmed cell death in Arabidopsis.

KEY MESSAGE: Cathepsin B plays an important role that degrades the Rubisco large subunit RbcL in freezing stress. Programmed cell death (PCD) has been well documented in both development and in response to environmental stresses in plants, however, PCD induced by freezing stress and its molecular mechanisms remain poorly understood. In the present study, we characterized freezing-induced PCD and explored its mechanisms in Arabidopsis. PCD induced by freezing stress was similar to that induced by other stresses and senescence in Arabidopsis plants with cold acclimation. Inhibitor treatment assays and immunoblotting indicated that cathepsin B mainly contributed to increased caspase-3-like activity during freezing-induced PCD. Cathepsin B was involved in freezing-induced PCD and degraded the large subunit, RbcL, of Rubisco. Our results demonstrate an essential regulatory mechanism of cathepsin B for Rubisco degradation in freezing-induced PCD, improving our understanding of freezing-induced cell death and nitrogen and carbohydrate remobilisation in plants.