Metabolic and Molecular Insights Into Nicotiana benthamiana Trichome Exudates: An Ammunition Depot for Plant Resistance Against Insect Pests.

Nicotiana benthamiana, a widely acknowledged laboratory model plant for molecular studies, exhibits lethality to certain insect pests and can serve as a dead-end trap plant for pest control in the field. However, the underlying mechanism of N. benthamiana's resistance against insects remains unknown. Here, we elucidate that the lethal effect of N. benthamiana on the whitefly Bemisia tabaci arises from the toxic glandular trichome exudates. By comparing the metabolite profiles of trichome exudates, we found that 51 metabolites, including five O-acyl sugars (O-AS) with medium-chain acyl moieties, were highly accumulated in N. benthamiana. Silencing of two O-AS biosynthesis genes, branched-chain keto acid dehydrogenase (BCKD) and Isopropyl malate synthase-C (IPMS-C), significantly reduced the O-AS levels in N. benthamiana and its resistance against whiteflies. Additionally, we demonstrated that the higher expression levels of BCKD and IPMS-C in the trichomes of N. benthamiana contribute to O-AS synthesis and consequently enhance whitefly resistance. Furthermore, overexpression of NbBCKD and NbIPMS-C genes in the cultivated tobacco Nicotiana tabacum enhanced its resistance to whiteflies. Our study revealed the metabolic and molecular mechanisms underlying the lethal effect of N. benthamiana on whiteflies and presents a promising avenue for improving whitefly resistance.

Attraction of Nicotiana benthamiana to Bemisia tabaci is related to a chemical signal in plant volatile, undecane.

BACKGROUND: The whitefly Bemisia tabaci is one of the world's foremost agricultural pests. Recently, we found that a wild relative of tobacco (Nicotiana benthamiana) demonstrates remarkable attractiveness and nearly 100% lethality towards whiteflies. Therefore, it can act as a dead-end trap crop for whitefly control in the field. However, the underlying mechanism of the significant attractiveness of N. benthamiana towards whiteflies is unclear. RESULTS: Binary-choice assays and olfactory experiments showed that compared to common tobacco (N. tabacum), the volatile of N. benthamiana has a greater attraction to whiteflies. Then we analyzed and compared volatiles from these two Nicotiana species by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). We identified 16 chemical compounds that are more abundant in N. benthamiana than in N. tabacum. Seven compounds were further tested with olfactometer assays and we found that, among them, undecane strongly attracted whiteflies. Further experiments revealed that even 0.005 µg mL-1 undecane is attractive to whiteflies. We also silenced the genes that may influence the biosynthesis of undecane and found the production of undecane decreased after silencing NbCER3, and that N. benthamiana plants with less undecane lost their attraction to whiteflies. In addition, we found that applying 0.005 µg mL-1 undecane on yellow sticky traps can increase the number of stuck insects on the traps by ≈40%. CONCLUSION: Undecane from the volatile of N. benthamiana is a critical chemical signal that attracts whiteflies and NbCER3 involved in the biosynthesis of undecane. Undecane may be used to improve the efficiency of yellow sticky traps for whitefly control. © 2024 Society of Chemical Industry.

Estrogen Oppositely Regulates Pulmonary Hypertension via METTL3/PFKFB3 Under Normoxia and Hypoxia.

Despite extensive investigation into estrogen's role in pulmonary hypertension (PH) development, its effects-whether beneficial or detrimental-remains contentious. This study aimed to elucidate estrogen's potential role in PH under normoxic and hypoxic conditions. Utilizing norfenfluramine- and hypoxia-induced rat models of PH, the study evaluated the impact of 17ß-estradiol (E2) on PH progression. E2 promoted PH development under normoxia while providing protection under hypoxia. Mechanistically, under normoxia, E2 upregulated methyltransferase-like 3 (METTL3) gene transcription and protein via an estrogen response element-dependent pathway, which in turn elevated the m6A methylation and translational efficiency of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) mRNA, leading to increased PFKFB3 protein levels and enhanced proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Conversely, under hypoxia, E2 downregulated METTL3 transcription through a hypoxia response element-dependent mechanism, driven by elevated hypoxia-induced factor 1α (HIF-1α) levels, resulting in reduced PFKFB3 protein expression and diminished PASMCs proliferation and migration. Both METTL3 and PFKFB3 proteins are upregulated in the pulmonary arteries of patients with PAH. Collectively, these findings suggest that E2 exerts differential effects on PH progression via dual regulation of the METTL3/PFKFB3 protein under normoxic and hypoxic conditions, positioning the METTL3/PFKFB3 protein as a potential therapeutic target for PH treatment.

Real-world effectiveness and safety of nirmatrelvir-ritonavir (Paxlovid)-treated for COVID-19 patients with onset of more than 5 days: a retrospective cohort study.

Background: Nirmatrelvir-ritonavir (Paxlovid) has received emergency use authorization from the US Food and Drug Administration owing to its effectiveness and safety. However, data on the effectiveness and safety of Paxlovid use in COVID-19 patients with onset of more than 5 days are lacking. Methods: A real-world retrospective study was performed during the outbreak involving the SARS-CoV-2 BA.5.2 subvariant. Hospitalized COVID-19 patients (including mild, moderate, severe and critical cases) were divided into three groups: Paxlovid treatment within (Group A) or more than (Group B) 5 days of COVID-19 onset and no Paxlovid treatment during more than 5 days of COVID-19 onset with only basic symptomatic treatment (Group C). Endpoints were all-cause 28-day mortality, improvement in clinical classification, and a composite endpoint of disease progression, viral load and virus elimination time. Safety was assessed by comparing adverse events reported during treatment in each group. Results: During the period, 248 hospitalized COVID-19 patients, including 55 in Group A, 170 in Group B, and 23 in Group C, were enrolled. There were no significant differences in the clinical classification improvement rate [80.0% (16/20) vs. 81.3% (52/64), p = 1.000; 60.0% (21/35) vs. 55.7% (59/106), p = 0.653, respectively] or all-cause 28-day mortality [0% (0/20) vs. 1.6% (1/64), p = 1.000; 11.4% (4/35) vs. 6.6% (7/106), p = 0.576, respectively] between Groups A and B for nonsevere and severe cases. However, the clinical classification improvement rate in Group B was markedly higher than that in Group C [81.3% (52/64) vs. 50.0% (6/12), p = 0.049] among nonsevere cases. Cycle threshold values of the N and ORF genes in Group B were significantly increased after Paxlovid treatment [31.14 (IQR 26.81-33.93) vs. 38.14 (IQR 36.92-40.00), p < 0.001; 31.33 (IQR 26.00-33.47) vs. 38.62 (IQR 35.62-40.00), p < 0.001, respectively]. No significant differences in reported adverse events of neurological disease (p = 0.571), liver injury (p = 0.960) or kidney injury (p = 0.193) between Group A and Group B were found. Conclusion: Paxlovid treatment within 10 days of onset can shorten the disease course of COVID-19 by reducing the viral load. Paxlovid is effective and safe in treating COVID-19 with onset of more than five or even 10 days when patients have a high viral load.

Three new ramarioid species of Phaeoclavulina (Gomphaceae, Gomphales) from China.

Three new species of Phaeoclavulina from China are described: Phaeoclavulinabicolor, P.echinoflava, and P.jilinensis. Recognition of the new species is supported by morphological and molecular evidence. Phylogenetic analyses of concatenated ITS1-5.8S-ITS2 and nuclear large subunit sequences support the establishment of the new species and their placement within the Phaeoclavulina clade. A key to the known Phaeoclavulina species in China is provided.

Steerable Interfacial Assembly of 1D Amyloid-Like Protein Nanocomposites for Enhanced Nanoherbicide Utilization.

Conventional herbicide formulations suffer from serious problems such as easy drift, run-off and scouring into the environment, which pose enormous threats to human health and environmental safety. Herein, an innovative strategy is proposed to prepare oil-in-water nanoemulsions with long-term stability, enhanced droplet deposition, and improved nanoherbicide adhesion via steerable interfacial assembly of 1D amyloid-like protein nanocomposites. Bovine serum albumin (BSA) undergoes rapid amyloid-like aggregation upon reduction of its disulfide bond. The resulting phase-transitioned BSA (PTB) oligomers instantly self-assemble on the surface of cellulose nanofibers (CNF) to form the 1D PTB/CNF nanocomposites, which greatly expands the parameter space for interfacial assembly of amyloid-like proteins. The PTB/CNF nanocomposites exhibit excellent interfacial activity, enabling spontaneous adsorption at the oil-water interface to stabilize nanoemulsion. The excess PTB/CNF nanocomposites would also self-assemble at the air-aqueous interface upon spraying, resulting in efficient droplet deposition on (super)hydrophobic leaves. The deposited nanoherbicides show excellent resistance to wind/rain corrosion due to the robust amyloid-mediated adhesion, with a retention rate of more than 80% after severe scouring. Consequently, herbicide applications can be reduced by at least 30% compared to commercial emulsifiable concentrates, showing greater herbicidal efficiency. This study provides novel insights and approaches to promote sustainable agricultural development.

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We isolated the dark septate endophytic (DSE) fungi from roots of typical plant species in the tundra of Changbai Mountains Nature Reserve, including Rhododendron aureum, R. conferentiatum, Vaccinium uliginosum, and Dryas octopetala, and studied their colonization. We further investigated the DSE community composition and species diversity of the four tundra plant species by using morphological characteristics combined with rDNA ITS sequence analysis. The results showed that DSE formed a typical structure of "microsclerotia" in roots of the four plant species. A total of 69 strains of DSE fungi were isolated from the root samples, belonging to 10 genera, and 12 species. They were Phialocephala fortinii, Alternaria alternata, A. tenuissima, Epicocum nigrum, Canariomyces microsporus, Colletotrichum spaethianum, C. camelliae, Leptophoria sp., Cladosporium cladosporioides, Phoma sp., Cadophora sp., and Discosia italica, respectively. The DSE fungal species diversity was rich, and all these fungal species were firstly reported as DSE fungi in the alpine tundra belt of China. Among them, Phialocephala fortinii was the common and dominant species of all tundra plants. The Simpson, Pielou, and Shannon diversity indices of DSE fungi of the four plant species of tundra differed significantly. Our results showed that tundra plants have rich diversity of DSE fungi, and they can form a good symbiotic relationship, which enhance the adaptability of tundra plants to the harsh environment.

Brucea javanica Seed Oil Emulsion and Shengmai Injections Improve Peripheral Microcirculation in Treatment of Gastric Cancer.

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. ß-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS: YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. ß-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.

Clinical characteristics and genomic profiling of outpatients with endometrial cancer at a Chinese tertiary cancer center.

OBJECTIVE: Endometrial cancer is stepping into the era of precision therapy. Genomic test is recommended for newly diagnostic patients. However, outpatients displayed more complex characteristics. Here, we elucidated the clinical characteristics and genomic profiling of outpatients with endometrial cancer at our institution. METHODS: Between 2018 and 2023, 68 endometrial cancer received genomic tests at outpatient department of Fudan University Shanghai Cancer Center. Data, including age, pathological histology, FIGO stage and treatment strategy were collected. Germline mutations, molecular subtypes and other somatic mutations were also summarized. RESULTS: Overall, 72.1% (49/68) of patients receive genomic tests at primary diagnosis, while 27.9% (19/68) of patients received tests at recurrence. Nine patients had deleterious germline mutations, including BRCA1(2), MLH1(1), MSH2(2, including one with co-mutation of RAD50), MSH6(2), FANCA(1), MUTYH(1). Molecular subtypes were recognized among 62 patients, as POLE super-mutation(4, 6.5%), MSI-H(7, 11.3%), CN-Low(36, 58.1%) and CN-High(15, 24.2%). Ten patients received anti-PD1 monotherapy or in combination with chemotherapy or anti-angiogenic therapy, with the duration of disease control of 1 to 35 months. The ORR rate was 30%, and six patients had stable disease. The median (range) follow-up time was 18(2-160) months. 23(33.8%) relapses were recorded, and CN-High subtype displayed worst PFS compared with other subtypes (P < 0.01). 6 deaths were reported including 2(5.6%) of CN-Low and 4(26.7%) of CN-High. CONCLUSION: Outpatients department gathered a considerable proportion of recurrent patients with complex genomic features. Patients with worse prognosis could be well studied, and anti-PD1 therapy was a promising salvage therapy in the real world.

Exosomal AC068768.1 enhances the proliferation, migration, and invasion of laryngeal squamous cell carcinoma through miR-139-5p/NOTCH1 axis.

Objective: Long non-coding RNAs (lncRNAs) are closely associated with the pathogenesis of laryngeal squamous cell carcinoma (LSCC). This study aimed to investigate the roles of AC068768.1 in LSCC. Methods: Exosomes were extracted by ultracentrifugation and identified by transmission electron microscopy (TEM) assay. The expression levels of mRNA and miRNA were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cellular functions were assesses through immunofluorescence, flow cytometry, colony formation, wound healing and transwell assays. Chromatin immunoprecipitation (ChIP) and luciferase assays were conducted to verify the binding of AC068768.1 by signal transducer and activator of transcription 3 (STAT3). Xenograft assays were performed to confirm the roles of AC068768.1 in LSCC, and hematoxylin-eosin (HE) staining was applied for histological analysis. Results: LSCC cell-derived exosomes induced M2-like tumor-associated macrophages (TAM2) polarization, which promoted the proliferation, migration, and invasion of LSCCs. Knockdown of exosomal AC068768.1 inhibited M2 polarization and suppressed LSCC aggressiveness both in vitro and in vivo. Moreover, AC068768.1 sponged miR-139-5p, inducing the upregulation of neurogenic locus notch homolog protein 1 (NOTCH1). LSCCs adapted to TAM2 polarization in the tumor microenvironment via AC068768.1-mediated activation of the NOTCH1 pathway. Additionally, NOTCH1 activated STAT3. Conclusion: The AC068768.1/miR-139-5p/NOTCH1/STAT3 axis promotes the metastasis of LSCC. This finding may provide a novel target for LSCC therapy.

PPIH as a poor prognostic factor increases cell proliferation and m6A RNA methylation in hepatocellular carcinoma.

RNA-binding proteins (RBPs) play a crucial role in the biological processes of liver hepatocellular carcinoma (LIHC). Peptidyl-prolyl cis-trans isomerase H (PPIH), an RBP, possesses prolyl isomerase activity and functions as a protein chaperone. The relationship between PPIH and LIHC has not yet been fully elucidated. This study elucidated potential mechanisms through which PPIH affects the prognosis of LIHC. Bioinformatics analysis and in vitro experiments revealed that PPIH expression was higher in LIHC tissues than in normal tissues. PPIH was identified as an independent prognostic factor, with high PPIH expression being associated with worse prognoses. Moreover, PPIH increased the m6A RNA methylation level and promoted cell proliferation by modulating DNA replication and the expression of cell cycle-related genes in LIHC cells. Bioinformatics analysis also revealed that PPIH expression increased immune cell infiltration and the expression of immune checkpoint proteins. Collectively, these findings indicate that PPIH might promote LIHC progression by enhancing the m6A RNA methylation level, increasing cell proliferation, and altering the tumor immune microenvironment. Our study demonstrates that PPIH, as a poor prognostic factor, may lead to LIHC malignancy through multiple pathways. Further in-depth research on this topic is warranted.

Aboveground biomass stocks of species-rich natural forests in southern China are influenced by stand structural attributes, species richness and precipitation.

Forests, the largest terrestrial carbon sinks, play an important role in carbon sequestration and climate change mitigation. Although forest attributes and environmental factors have been shown to impact aboveground biomass, their influence on biomass stocks in species-rich forests in southern China, a biodiversity hotspot, has rarely been investigated. In this study, we characterized the effects of environmental factors, forest structure, and species diversity on aboveground biomass stocks of 30 plots (1 ha each) in natural forests located within seven nature reserves distributed across subtropical and marginal tropical zones in Guangxi, China. Our results indicate that forest aboveground biomass stocks in this region are lower than those in mature tropical and subtropical forests in other regions. Furthermore, we found that aboveground biomass was positively correlated with stand age, mean annual precipitation, elevation, structural attributes and species richness, although not with species evenness. When we compared stands with the same basal area, we found that aboveground biomass stock was higher in communities with a higher coefficient of variation of diameter at breast height. These findings highlight the importance of maintaining forest structural diversity and species richness to promote aboveground biomass accumulation and reveal the potential impacts of precipitation changes resulting from climate warming on the ecosystem services of subtropical and northern tropical forests in China. Notably, many natural forests in southern China are not fully stocked. Therefore, their continued growth will increase their carbon storage over time.

Immunoproteasome acted as immunotherapy 'coffee companion' in advanced carcinoma therapy.

Immunoproteasome is a specialized form of proteasome which plays a crucial role in antigen processing and presentation, and enhances immune responses against malignant cells. This review explores the role of immunoproteasome in the anti-tumor immune responses, including immune surveillance and modulation of the tumor microenvironment, as well as its potential as a target for cancer immunotherapy. Furthermore, we have also discussed the therapeutic potential of immunoproteasome inhibitors, strategies to enhance antigen presentation and combination therapies. The ongoing trials and case studies in urology, melanoma, lung, colorectal, and breast cancers have also been summarized. Finally, the challenges facing clinical translation of immunoproteasome-targeted therapies, such as toxicity and resistance mechanisms, and the future research directions have been addressed. This review underscores the significance of targeting the immunoproteasome in combination with other immunotherapies for solid tumors and its potential broader applications in other diseases.

Advancing Heterogeneous Organic Synthesis With Coordination Chemistry-Empowered Single-Atom Catalysts.

For traditional metal complexes, intricate chemistry is required to acquire appropriate ligands for controlling the electron and steric hindrance of metal active centers. Comparatively, the preparation of single-atom catalysts is much easier with more straightforward and effective accesses for the arrangement and control of metal active centers. The presence of coordination atoms or neighboring functional atoms on the supports' surface ensures the stability of metal single-atoms and their interactions with individual metal atoms substantially regulate the performance of metal active centers. Therefore, the collaborative interaction between metal and the surrounding coordination environment enhances the initiation of reaction substrates and the formation and transformation of crucial intermediate compounds, which imparts single-atom catalysts with significant catalytic efficacy, rendering them a valuable framework for investigating the correlation between structure and activity, as well as the reaction mechanism of catalysts in organic reactions. Herein, comprehensive overviews of the coordination interaction for both homogeneous metal complexes and single-atom catalysts in organic reactions are provided. Additionally, reflective conjectures about the advancement of single-atom catalysts in organic synthesis are also proposed to present as a reference for later development.

Engineering an Epoxide Hydrolase for Chemoenzymatic Asymmetric Synthesis of Chiral Triazole Fungicide (S)- and (R)-Flutriafol.

Flutriafol, a globally utilized triazole fungicide in agriculture, is typically applied as a racemic mixture, but its enantiomers differ in bioactivity and environmental impact. The synthesis of flutriafol enantiomers is critically dependent on chiral precursors: 2,2-bisaryl-substituted oxirane [(2-fluorophenyl)-2-(4-fluorophenyl)oxirane, 1a] and 1,2-diol [1-(2-fluorophenyl)-1-(4-fluorophenyl)ethane-1,2-diol, 1b]. Here, we engineered a Rhodotorula paludigensis epoxide hydrolase (RpEH), obtaining mutant Escherichia coli/RpehH336W/L360F with a 6.4-fold enhanced enantiomeric ratio (E) from 5.5 to 35.4. This enabled a gram-scale resolution of rac-1a by E. coli/RpehH336W/L360F, producing (S)-1a (98.2% ees) and (R)-1b (75.0% eep) with 44.3 and 55.7% analytical yields, respectively. As follows, chiral (S)-flutriafol (98.2% ee) and (R)-flutriafol (75.0% ee) were easily synthesized by a one-step chemocatalytic process from (S)-1a and a two-step chemocatalytic process from (R)-1b, respectively. This chemoenzymatic approach offers a superior alternative for the asymmetric synthesis of flutriafol enantiomers. Furthermore, molecular dynamics simulations revealed insight into the enantioselectivity improvement of RpEH toward bulky 2,2-bisaryl-substituted oxirane 1a.

Preparation of monoclonal antibodies recognizing pharmacologically active metabolites of metamizole based on rational hapten design and their application in the detection of animal-derived food.

Metamizole (MET) is an antipyretic and analgesic drug, the illegal use of which can result in residues of MET metabolites in edible tissues of animals. In this study, a computational chemistry-assisted hapten screening strategy was used to screen for the optimal immunogenic hapten-A and the optimal coating antigen hapten-G-OVA. A monoclonal antibody capable of recognizing two pharmacologically active metabolites of MET, 4-methylamidinoantipyrine (MAA) and 4-aminoantipyrine (AA), was prepared from the hapten-A. The antibody showed excellent specificity for MAA and AA and almost no cross-reactivity with the pharmacologically inactive metabolites 4-formamidinoantipyrine (FAA) and 4-acetamidinoantipyrine (AAA). An ic-ELISA was developed for the simultaneous detection of MAA and AA in animal-derived food, the limits of detection for MAA ranged from 0.93 to 1.18 µg/kg, while those for AA ranged from 1.74 to 4.61 µg/kg. The recovery rate fell within the range of 82 %-110 %, with a coefficient of variation less than 16.39 %.

Retrospective analysis based on a clinical grading system for patients with hepatic hemangioma: A single center experience.

BACKGROUND: The optimal approach for managing hepatic hemangioma is controversial. AIM: To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience. METHODS: A clinical grading system was retrospectively applied to 1171 patients with hepatic hemangioma from January 2002 to December 2018. Patients were classified into four groups based on the clinical grading system and treatment: (1) Observation group with score < 4 (Obs score < 4); (2) Surgical group with score < 4 (Sur score < 4); (3) Observation group with score ≥ 4 (Obs score ≥ 4); and (4) Surgical group with score ≥ 4 (Sur score ≥ 4). The clinico-pathological index and outcomes were evaluated. RESULTS: There were significantly fewer symptomatic patients in surgical groups (Sur score ≥ 4 vs Obs score ≥ 4, P < 0.001; Sur score < 4 vs Obs score < 4, χ² = 8.60, P = 0.004; Sur score ≥ 4 vs Obs score < 4, P < 0.001). The patients in Sur score ≥ 4 had a lower rate of in need for intervention and total patients with adverse event than in Obs score ≥ 4 (P < 0.001; P < 0.001). Nevertheless, there was no significant difference in need for intervention and total patients with adverse event between the Sur score < 4 and Obs score < 4 (P > 0.05; χ² = 1.68, P > 0.05). CONCLUSION: This clinical grading system appeared as a practical tool for hepatic hemangioma. Surgery can be suggested for patients with a score ≥ 4. For those with < 4, follow-up should be proposed.

STOP1 regulates CCX1-mediated Ca2+ homeostasis for plant adaptation to Ca2+ deprivation.

Calcium (Ca) is essential for plant growth and stress adaptation, yet its availability is often limited in acidic soils, posing a major threat to crop production. Understanding the intricate mechanisms orchestrating plant adaptation to Ca deficiency remains elusive. Here, we show that the Ca deficiency-enhanced nuclear accumulation of the transcription factor SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1) in Arabidopsis thaliana confers tolerance to Ca deprivation, with the global transcriptional responses triggered by Ca deprivation largely impaired in the stop1 mutant. Notably, STOP1 activates the Ca deprivation-induced expression of CATION/Ca2+ EXCHANGER 1 (CCX1) by directly binding to its promoter region, which facilitates Ca2+ efflux from endoplasmic reticulum to cytosol to maintain Ca homeostasis. Consequently, the constitutive expression of CCX1 in the stop1 mutant partially rescues the Ca deficiency phenotype by increasing Ca content in the shoots. These findings uncover the pivotal role of the STOP1-CCX1 axis in plant adaptation to low Ca, offering alternative manipulating strategies to improve plant Ca nutrition in acidic soils and extending our understanding of the multifaceted role of STOP1.

Efficacy and mechanism of energy metabolism dual-regulated nanoparticles (atovaquone-albendazole nanoparticles) against cystic echinococcosis.

BACKGROUND: Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs. METHODS: Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity. RESULTS: Drug NPs are characterized by uniform particle size, stability, high drug loading, and - 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes. CONCLUSION: ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.