Strigolactone enhances tea plant adaptation to drought and Phyllosticta theicola petch by regulating caffeine content via CsbHLH80.

Strigolactones (SLs) play crucial roles in both plant growth and stress responses. However, their impact on the secondary metabolites of woody plants remains elusive. Here, we found that exogenous strigolactone analogue GR24 positively regulates tea plant flavor secondary metabolites, concurrently inhibiting caffeine biosynthesis and promoting the accumulation of caffeine catabolic pathway products. In this process, SL directly or indirectly inhibits the expression of CsSAMSs by inducing CsbHLH80, thereby reducing caffeine biosynthesis. Furthermore, CsbHLH80 enhances caffeine degradation, leading to increased allantoin. Under normal conditions, heightened allantoin reduces abscisic acid (ABA) accumulation. This inhibition reverses under drought stress. Increased ABA significantly enhances tea plant tolerance to both drought and Phyllosticta theicola Petch. In summary, this study offers novel insights for improving tea plant adaptation and quality in arid regions, particularly emphasizing the selection of stress-tolerant varieties and the refinement of production measures with a focus on high-quality production and environmentally friendly biological control methods.

Hydrogel-Mediated Jamming of Exosome Communications That Counter Tumor Adaption in the Tumor Immune Microenvironment.

Hypoxia, a common occurrence within solid tumors, can stimulate the dissemination of deceptive tumor exosomes, which function as communicative bridges and orchestrate the recruitment of various supportive cell types for enhanced tumor adaptability in a tumor immune microenvironment. Current nanotechnology provides us intelligent strategies to combat the hypoxic tumor microenvironment. However, once exposed to external stimuli, such as chemotherapy, tumor cells simultaneously release malignant signals to develop tumor migration and immunosuppression, posing challenges to clinical practice. Taking advantage of the membrane-targeting therapeutic strategy, the application of a self-assembled short peptide (PepABS-py), affording hydrogels on tumor cell surfaces, can block exosome dissemination with fiber-like nanostructures and effectively limit the systemic adverse effects of traditional therapeutics. Moreover, PepABS-py can attenuate the hypoxic tumor microenvironment in vivo by carrying an inhibitor of the hypoxic tumor-overexpressed CA IX enzyme, where hypoxia is also a crucial regulator to induce tumor exosomes and mediate intercellular communications within the immune system. Herein, its application on jamming exosome communications can target the T cell-related signaling pathway by regulating microRNAs in exosome cargoes and ultimately enhances CD8+ T cell infiltration and alleviates inflammatory monocytes at metastasis sites. Collectively, with the capability of blocking exosome dissemination, PepABS-py can be applied as a promising tumor membrane-targeting therapeutic tool to counter tumor adaption within an immune microenvironment and further advance traditional chemotherapy.

Loss of Lateral suppressor gene is associated with evolution of root nodule symbiosis in Leguminosae.

BACKGROUND: Root nodule symbiosis (RNS) is a fascinating evolutionary event. Given that limited genes conferring the evolution of RNS in Leguminosae have been functionally validated, the genetic basis of the evolution of RNS remains largely unknown. Identifying the genes involved in the evolution of RNS will help to reveal the mystery. RESULTS: Here, we investigate the gene loss event during the evolution of RNS in Leguminosae through phylogenomic and synteny analyses in 48 species including 16 Leguminosae species. We reveal that loss of the Lateral suppressor gene, a member of the GRAS-domain protein family, is associated with the evolution of RNS in Leguminosae. Ectopic expression of the Lateral suppressor (Ls) gene from tomato and its homolog MONOCULM 1 (MOC1) and Os7 from rice in soybean and Medicago truncatula result in almost completely lost nodulation capability. Further investigation shows that Lateral suppressor protein, Ls, MOC1, and Os7 might function through an interaction with NODULATION SIGNALING PATHWAY 2 (NSP2) and CYCLOPS to repress the transcription of NODULE INCEPTION (NIN) to inhibit the nodulation in Leguminosae. Additionally, we find that the cathepsin H (CTSH), a conserved protein, could interact with Lateral suppressor protein, Ls, MOC1, and Os7 and affect the nodulation. CONCLUSIONS: This study sheds light on uncovering the genetic basis of the evolution of RNS in Leguminosae and suggests that gene loss plays an essential role.

Achieving High OER Performance by Tuning the Co/Mn Content in Prussian Blue Analogues.

The need for efficient, economical, and clean energy systems is increasing, and as a result, interest in water-splitting techniques to produce green hydrogen is also increasing. However, the sluggish kinetics of the oxygen evolution reaction (OER) hinders the practical application and widespread use of water-splitting technologies; therefore, to address this challenge, it is essential to develop cost-effective and efficient OER catalysts. In this work, we have synthesized an inexpensive and tunable FeCoMn Prussian blue analogue (PBAs) as an efficient OER catalyst via a straightforward process. The ratio of the Co and Mn to optimize the electrochemical performance, and as a result, the FeCo0.41Mn0.42 PBA catalyst demonstrated the best electrochemical performance (260/304 mV overpotential at 10/50 mA cm-2, a low Tafel slope of 48 mV dec-1 and a good stability of 72 h at 10 mA cm-2). Additionally, X-ray absorption spectroscopy (XAS) measurements and density functional theory (DFT) calculations suggest that the FeCo0.41Mn0.42 PBA possesses the optimized electronic density distribution at the active site (Co), and the doping of Mn and Fe can not only increase the electricity conductivity but also activate the critical H2O deprotonation step.

JPH203 alleviates peritoneal fibrosis via inhibition of amino acid-mediated mTORC1 signaling.

BACKGROUND AND AIMS: The mesothelial-mesenchymal transition (MMT) of mesothelial cells has been recognized as a critical process during progression of peritoneal fibrosis (PF). Despite its crucial role in amino acid transport and metabolism, the involvement of L-type amino acid transporter 1 (LAT1) and the potential therapeutic role of its inhibitor, JPH203, in fibrotic diseases remain unexplored. Considering the paucity of research on amino acid-mediated mTORC1 activation in PF, our study endeavors to elucidate the protective effects of JPH203 against PF and explore the involvement of amino acid-mediated mTORC1 signaling in this context. METHODS: We established the transforming growth factor beta 1 (TGF-ß1) induced MMT model in primary human mesothelial cells and the peritoneal dialysis fluid (PDF) induced PF model in mice. The therapeutic effects of JPH203 on PF were then examined on these two models by real-time quantitative polymerase chain reaction, western blotting, immunofluorescence staining, Masson's trichrome staining, H&E staining, picro-sirius red staining, and immunohistochemistry. The involvement of amino acid-mediated mTORC1 signaling was screened by RNA sequencing and further verified by western blotting in vitro. RESULTS: LAT1 was significantly upregulated and JPH203 markedly attenuated fibrotic phenotype both in vitro and in vivo. RNA-seq unveiled a significant enrichment of mTOR signaling pathway in response to JPH203 treatment. Western blotting results indicated that JPH203 alleviates PF by inhibiting amino acid-mediated mTORC1 signaling, which differs from the direct inhibition observed with rapamycin. CONCLUSION: JPH203 alleviates PF by inhibiting amino acid-mediated mTORC1 signaling.

Overall Survival in Real-World Patients with Unresectable Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab Versus Sorafenib or Lenvatinib as First-Line Therapy: Findings from the National Veterans Health Administration Database.

Background/Objectives: This study evaluated comparative overall survival (OS) of United States veterans with unresectable hepatocellular carcinoma (uHCC) receiving first-line (1L) atezolizumab plus bevacizumab vs. sorafenib or lenvatinib, overall and across racial and ethnic groups. Methods: In this retrospective study, patients with uHCC who initiated atezolizumab plus bevacizumab (post-2020) or sorafenib or lenvatinib (post-2018) were identified from the Veterans Health Administration National Corporate Data Warehouse (1 January 2017-31 December 2022). Patient characteristics were evaluated in the year prior to 1L treatment initiation. Kaplan-Meier and multivariable Cox regression methods were used to compare OS starting from treatment between cohorts, both overall and by race and ethnicity. Results: Among the 1874 patients included, 405 (21.6%) received 1L atezolizumab plus bevacizumab, 1016 (54.2%) received sorafenib, and 453 (24.2%) received lenvatinib, with a median follow-up time of 8.5, 7.6, and 8.2 months, respectively. Overall, patients receiving atezolizumab plus bevacizumab had longer unadjusted median OS (12.8 [95% CI: 10.6, 17.1] months) than patients receiving sorafenib (8.0 [7.1, 8.6] months) or lenvatinib (9.5 [7.8, 11.4] months; both log-rank p < 0.001). After adjustment, atezolizumab plus bevacizumab was associated with a reduced risk of death by 30% vs. sorafenib (adjusted HR: 0.70 [95% CI: 0.60, 0.82]) and by 26% vs. lenvatinib (0.74 [0.62, 0.88]; both p < 0.001). OS trends in the White, Black, and Hispanic patient cohorts were consistent with that of the overall population. Conclusions: Atezolizumab plus bevacizumab was associated with improved survival outcomes compared with sorafenib and lenvatinib in patients with uHCC, both overall and across racial and ethnic subgroups.

Chemotherapy Combined With Endocrine Therapy: Old Wine in a New Bottle?

Both chemotherapy (CT) and endocrine therapy (ET) play important roles in the systemic treatment of breast cancer (BC). However, previous studies have shown an antagonistic effect when CT and ET are administered simultaneously. Therefore, sequential administration is more effective than combined administration. The current guidelines and consensus recommend a sequential schedule of CT and ET for patients with hormone receptor-positive (HR+) BC. However, with the continuous introduction of new endocrine drugs, the question of whether the simultaneous administration of CT and ET is superior to sequential therapy has surfaced again as a hot topic of clinical concern. Recent studies have shown that the combination of certain chemotherapeutic agents with endocrine drugs has a synergistic effect. This review aims to summarize the new advances achieved in recent years on the old topic of CT combined with ET in the treatment of BC.

Interactions of Saccharomyces cerevisiae and Lactiplantibacillus plantarum Isolated from Light-Flavor Jiupei at Various Fermentation Temperatures.

Chinese Baijiu is a famous fermented alcoholic beverage in China. Interactions between key microorganisms, i.e., Saccharomyces cerevisiae and Lactiplantibacillus plantarum, have recently been reported at specific temperatures. However, empirical evidence of their interactions at various temperatures during fermentation is lacking. The results of this study demonstrated that S. cerevisiae significantly suppressed the viability and lactic acid yield of L. plantarum when they were cocultured above 15 °C. On the other hand, L. plantarum had no pronounced effect on the growth and ethanol yield of S. cerevisiae in coculture systems. S. cerevisiae was the main reducing sugar consumer. Inhibition of lactic acid production was also observed when elevated cell density of L. plantarum was introduced into the coculture system. A proteomic analysis indicated that the enzymes involved in glycolysis, lactate dehydrogenase, and proteins related to phosphoribosyl diphosphate, ribosome, and aminoacyl-tRNA biosynthesis in L. plantarum were less abundant in the coculture system. Collectively, our data demonstrated the antagonistic effect of S. cerevisiae on L. plantarum and provided insights for effective process management in light-flavor Baijiu fermentation.

Outcomes of extracorporeal membrane oxygenation cannulation strategy in lung transplantation: A retrospective cohort study.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) with different cannulation strategies is determined according to surgical position and patient condition. However, no cannulation guidelines have been proposed. This retrospective study assessed the outcomes of diverse ECMO cannulation strategies in patients undergoing lung transplantation (LTx). METHODS: Data of patients undergoing intraoperative veno-arterial ECMO-assisted LTx were retrospectively collected from December 1st, 2015 to October 31st, 2021. Patients were classified into three groups based on the different cannulation strategies: femoral artery-femoral vein (F-F)-ECMO, axillary artery-femoral vein (A-F)-ECMO, and ascending aorta-femoral vein (AAO-F)-ECMO. The F-F-ECMO, A-F-ECMO, and AAO-F-ECMO groups comprised 34, 44, and 30 patients, respectively. MAIN RESULTS: The AAO-F-ECMO group exhibited a significantly shorter duration of postoperative ECMO therapy (3 vs. 2 vs. 0 days, P < 0.01).the level of postoperative proBNP was lower on the third and seventh days (P < 0.001). AAO-F-ECMO patients had a significantly lower incidence of postoperative infections, heart failure, and bleeding (P < 0.05). Similar outcomes were observed in postoperative survival rates among the three groups (P > 0.05). CONCLUSIONS: Ascending aorta-femoral vein ECMO can provide sufficient and effective aerobic blood to perfuse organs with fewer side effects than cannulation in the femoral artery-femoral vein or axillary artery-femoral vein.

Fine-tuning of IPA1 transactivation activity by E3 ligase IPI7-mediated non-proteolytic K29-ubiquitination during Magnaporthe oryzae infection.

The Ideal Plant Architecture 1 (IPA1) transcription factor promotes rice yield and immunity through phosphorylation at its amino acid residue Ser163 as a switch. Although phosphorylated IPA1 mimic, IPA1(S163D), directly targets the promoter of immune response gene WRKY45, it cannot activate its expression. Here, we identified a co-activator of IPA1(S163D), a RING-finger E3 ligase IPA1 interactor 7 (IPI7), which fine-tunes the transcriptional activity of IPA1 to timely promote plant immunity and simultaneously maintain growth for yield. IPI7 interacts with IPA1 and promotes K29-polyubiquitination of IPA1 in vitro and in vivo. However, the stability of IPA1 protein is not affected by IPI7-mediated ubiquitination. The IPI7-promoted K29-polyubiquitination of IPA1 is induced by Magnaporthe oryzae infection and required for phosphorylated IPA1 to transactivate WRKY45 expression for immune response but not for plain IPA1 to transactivate DENSE AND ERECT PANICLES 1 (DEP1) expression for panicle development. IPI7 knockout impairs IPA1-mediated immunity but not yield. Our study reveals that plants utilize non-proteolytic K29-ubiquitination as a response to pathogen infection to fine-tune IPA1 transactivation activity for promoting immunity.

Reviving Sodium Tunnel Oxide Cathodes Based on Structural Modulation and Sodium Compensation Strategy Toward Practical Sodium-Ion Cylindrical Battery.

As a typical tunnel oxide, Na0.44MnO2 features excellent electrochemical performance and outstanding structural stability, making it a promising cathode for sodium-ion batteries (SIBs). However, it suffers from undesirable challenges such as surface residual alkali, multiple voltage plateaus, and low initial charge specific capacity. Herein, an internal and external synergistic modulation strategy is adopted by replacing part of the Mn with Ti to optimize the bulk phase and construct a Ti-containing epitaxial stabilization layer, resulting in reduced surface residual alkali, excellent Na+ transport kinetics and improved water/air stability. Specifically, the Na0.44Mn0.85Ti0.15O2 using water-soluble carboxymethyl cellulose as a binder can realize a capacity retention rate of 94.30% after 1,000 cycles at 2C, and excellent stability is further verified in kilogram large-up applications. In addition, taking advantage of the rich Na content in Prussian blue analog (PBA), PBA-Na0.44Mn1-xTixO2 composites are designed to compensate for the insufficient Na in the tunnel oxide and are matched with hard carbon to achieve the preparation of coin full cell and 18650 cylindrical battery with satisfactory electrochemical performance. This work enables the application of tunnel oxides cathode for SIBs in 18650 cylindrical batteries for the first time and promotes the commercialization of SIBs.

Improving Seed Shattering Resistance in Wild O. alta Rice with Mesoporous Silica Nanoparticle Delivery Systems.

To address food security challenges and climate change, the polyploid wild rice Oryza alta has been explored as a potential crop, although it suffers from seed shattering. We employed mesoporous silica nanoparticles (MSNs) to deliver small interfering RNAs (siRNAs) for targeted gene silencing. Foliar spraying of MSN-siRNA complexes effectively delivered siRNA, resulting in up to 70% gene silencing of the PDS gene and 75% silencing of the transgenic Ruby gene. Additionally, MSN-siRNAs were infiltrated into the panicles of O. alta to target four seed shattering major genes every other day for 2 weeks until heading outdoors. This method silenced all four shattering genes ranging from 10.7% to 49.4% and significantly reduced the formation of the abscission layer between rice grains and pedicels, which enhanced pedicel tensile strength. Our MSN-siRNA system provides a flexible, nonpermanent approach to modifying crop traits, offering a promising tool for sustainable agricultural practices.

Robot-assisted resection of ganglion cell neuroma with a diameter of 78 mm: A case report.

RATIONALE: Intrathoracic paragangliomas are typically found within the intricate posterior mediastinal region adjacent to the vertebrae, often presenting with substantial volume. Surgical excision of such tumors presents formidable challenges and is conventionally performed via open surgical procedures. PATIENT CONCERNS: In this report, we present the case of a 53-year-old female patient who presented with the discovery of a left intrathoracic mass during a routine physical examination approximately 1 month prior. She complained of chest tightness and chest pain. DIAGNOSES: She complained of chest tightness and chest pain. Magnetic resonance imaging of the chest and brachial plexus revealed a mass adjacent to the left upper lung hilum, measuring approximately 78 × 63 × 72 mm. The initial suspicion leaned towards a benign lesion. Notably, there was slight compression of the left first thoracic nerve root and mild compression of the middle and lower trunks of the left brachial plexus. Based on the morphological features of the tumor and imaging findings, we suspected its benign nature. INTERVENTIONS: We opted for robot-assisted thoracic surgery to resect the mediastinal tumor. OUTCOMES: Subsequent postoperative pathology confirmed the diagnosis as a paraganglioma. The patient did not experience any notable complications post-surgery, and a 6-month follow-up revealed no signs of recurrence. LESSONS: The successful application of the robot-assisted thoracic surgery surgical technique underscores its efficacy in minimally invasive resection of sizable intrathoracic tumors situated in the posterior mediastinum.

Membrane-camouflaged biomimetic nanoplatform with arsenic complex for synergistic reinforcement of liver cancer therapy.

Aim: Arsenic has excellent anti-advanced liver cancer effects through a variety of pathways, but its severe systemic toxicity forces the need for a safe and effective delivery strategy.Methods: Based on the chelating metal ion properties of polydopamine (PDA), arsenic was immobilized on an organic carrier, and a M1-like macrophage cell membrane (MM)-camouflaged manganese-arsenic complex mesoporous polydopamine (MnAsOx@MP@M) nanoplatform was successfully constructed. MnAsOx@MP@M was evaluated at the cellular level for tumor inhibition and tumor localization, and in vivo for its anti-liver cancer effect in a Hepa1-6 tumor-bearing mouse model.Results: The nanoplatform targeted the tumor site through the natural homing property of MM, completely degraded and released drugs to kill tumor cells in an acidic environment, while playing an immunomodulatory role in promoting tumor-associated macrophages (TAMs) repolarization.Conclusion: MnAsOx@MP@M has synergistically enhanced the targeted therapeutics against liver cancer via nanotechnology and immunotherapy, and it is expected to become a safe and multifunctional treatment platform in clinical oncology.

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Duplication and sub-functionalization of flavonoid biosynthesis genes plays important role in Leguminosae root nodule symbiosis evolution.

Gene innovation plays an essential role in trait evolution. Rhizobial symbioses, the most important N2-fixing agent in agricultural systems that exists mainly in Leguminosae, is one of the most attractive evolution events. However, the gene innovations underlying Leguminosae root nodule symbiosis (RNS) remain largely unknown. Here, we investigated the gene gain event in Leguminosae RNS evolution through comprehensive phylogenomic analyses. We revealed that Leguminosae-gain genes were acquired by gene duplication and underwent a strong purifying selection. Kyoto Encyclopedia of Genes and Genomes analyses showed that the innovated genes were enriched in flavonoid biosynthesis pathways, particular downstream of chalcone synthase (CHS). Among them, Leguminosae-gain type Ⅱ chalcone isomerase (CHI) could be further divided into CHI1A and CHI1B clades, which resulted from the products of tandem duplication. Furthermore, the duplicated CHI genes exhibited exon-intron structural divergences evolved through exon/intron gain/loss and insertion/deletion. Knocking down CHI1B significantly reduced nodulation in Glycine max (soybean) and Medicago truncatula; whereas, knocking down its duplication gene CHI1A had no effect on nodulation. Therefore, Leguminosae-gain type Ⅱ CHI participated in RNS and the duplicated CHI1A and CHI1B genes exhibited RNS functional divergence. This study provides functional insights into Leguminosae-gain genetic innovation and sub-functionalization after gene duplication that contribute to the evolution and adaptation of RNS in Leguminosae.

Optimizing carbon sources on performance for enhanced efficacy in single-stage aerobic simultaneous nitrogen and phosphorus removal via biofloc technology.

Bioflocs can efficiently achieve simultaneous nitrate and phosphate removal through a single-stage aerobic process, provided they are continuously supplemented with an organic carbon source. This study investigated the effects of different carbon sources on this process. Results revealed that phosphate removal rate in the glucose group was 0.61 ± 0.02 mg/L/h, significantly higher than those in the acetate (0.28 ± 0.01 mg/L/h) and propionate (0.29 ± 0.03 mg/L/h) groups (p < 0.05). However, the three groups observed no significant differences in nitrate removal rates (p > 0.05). The superior performance of the glucose group in simultaneous nitrogen and phosphorus removal is likely due to the higher biomass synthesis. In contrast, nitrate removal in the acetate and propionate groups was primarily driven by denitrification, resulting in lower sludge production and reduced phosphate uptake. For practical application of bioflocs in simultaneous nitrogen and phosphorus removal, glucose is recommended as the optimal carbon source.

Ferroptosis in the adjuvant treatment of lung cancer-the potential of selected botanical drugs and isolated metabolites.

Ferroptosis represents a distinct form of cell death that is not associated with necrosis, autophagy, apoptosis, or pyroptosis. It is characterised by intracellular iron-dependent lipid peroxidation. The current literature indicates that a number of botanical drugs and isolated metabolites can modulate ferroptosis, thereby exerting inhibitory effects on lung cancer cells or animal models. The aim of this review is to elucidate the mechanisms through which botanical drugs and isolated metabolites regulate ferroptosis in the context of lung cancer, thereby providing potential insights into lung cancer treatment. It is crucial to highlight that these preclinical findings should not be interpreted as evidence that these treatments can be immediately translated into clinical applications. In the future, we will continue to study the pharmacology, pharmacokinetics and toxicology of these drugs, as well as evaluating their efficacy and safety in clinical trials, with the aim of providing new approaches to the development of new agents for the treatment of lung cancer.

Selective recognition of PTRE1 transcripts mediated by protein-protein interaction between the m6A reader ECT2 and PTRE1.

N6-methyladenosine (m6A) is a prevalent internal post-transcriptional modification in eukaryotic RNAs executed by m6A-binding proteins known as "readers." Our previous research demonstrated that the Arabidopsis m6A reader ECT2 positively regulates transcript levels of the proteasome regulator PTRE1 and several 20S proteasome subunits, thereby enhancing 26S proteasome activity. However, mechanism underlying the selective recognition of m6A targets by readers, such as ECT2, remains elusive. In this study, we further demonstrate that ECT2 physically interacts with PTRE1 and several 20S proteasome subunits. This interaction, which occurs on the ribosome, involves the N terminus of PTRE1, suggesting that ECT2 might bind to the nascent PTRE1 polypeptide. Deleting ECT2's protein interaction domain impairs its mRNA-binding ability, whereas mutations in the m6A-RNA-binding site do not affect protein-protein interactions. Moreover, introducing a novel protein-binding domain into ECT2 increases transcript levels of proteins interacting with this domain. Our findings indicate that interaction with the PTRE1 protein enhances ECT2's binding to PTRE1 m6A mRNAs during translation, thereby regulating PTRE1 mRNA levels.