A covalent organic framework nanosheet-nanochannel composite with signal amplification strategy for electrochemical enantioselective recognition.

Recognition and separation of chiral isomers are of great importance in both industrial and biological applications. However, owing to identical molecular formulas and chemical properties of enantiomers, signal transduction and amplification are still two major challenges in chiral sensing. In this study, we developed an enantioselective device by integrating chiral covalent organic framework nanosheets (CONs) with nanochannels for sensitive identification and quantification of enantiomers. Using 3,4-dihydroxyphenylalanine (DOPA) as the model analyte, the as-prepared chiral nanofluidic device exhibits a remarkable chiral recognition ability to l-DOPA than d-DOPA. More importantly, due to the chelation of DOPA with Fe3+ ions, it can efficiently block the ion transport through channel and shield the channel surface charge, which will amplify the difference in the electrochemical response of l-DOPA and d-DOPA. Therefore, a sensitive chiral recognition can be achieved using the present nanofluidic device coupled using electrochemical amplification strategy. Notably, using this method, an ultra-low concentration of l-DOPA (as low as 0.21 pM) can be facilely and successfully detected with a linear range of 1 pM-10 µM. This study provides a reliable and sensitive approach for achieving highly selective detection of chiral molecules.

The rice E3 ubiquitin ligase-transcription factor module targets two trypsin inhibitors to enhance broad-spectrum disease resistance.

Broad-spectrum disease resistance (BSR) is crucial for controlling plant diseases and relies on immune signals that are subject to transcriptional and post-translational regulation. How plants integrate and coordinate these signals remains unclear. We show here that the rice really interesting new gene (RING)-type E3 ubiquitin ligase OsRING113 targets APIP5, a negative regulator of plant immunity and programmed cell death (PCD), for 26S proteasomal degradation. The osring113 mutants in Nipponbare exhibited decreased BSR, while the overexpressing OsRING113 plants showed enhanced BSR against Magnaporthe oryzae (M. oryzae) and Xanthomonas oryzae pv. oryzae (Xoo). Furthermore, APIP5 directly suppressed the transcription of the Bowman-Birk trypsin inhibitor genes OsBBTI5 and AvrPiz-t-interacting protein 4 (APIP4). Overexpression of these two genes, which are partially required for APIP5-mediated PCD and disease resistance, conferred BSR. OsBBTI5 and APIP4 associated with and stabilized the pathogenesis-related protein OsPR1aL, which promotes M. oryzae resistance. Our results identify an immune module with integrated and coordinated hierarchical regulations that confer BSR in plants.

OsEIL2 balances rice immune responses against (hemi)biotrophic and necrotrophic pathogens via the salicylic acid and jasmonic acid synergism.

Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes.

Genistein-Chitosan Derivative Nanoparticles for Targeting and Enhancing the Anti-Breast Cancer Effect of Tamoxifen In Vitro.

Tamoxifen (TAM) is a classical anti-estrogenic drug that antagonizes estrogen by competitively binding to estrogen receptor α (ERα). However, drug resistance to TAM remains a significant challenge in breast cancer treatment. In this study, we aimed to design an actively targeted drug delivery system to enhance the proliferation inhibitory effects of TAM on ER positive breast cancer cells. Herein, chitosan (CS) was modified with genistein (GEN) to obtain the actively targeted GEN-CS. The TAM-loaded nanoparticles (TAM-GEN-CS-NPs) were constructed using an ionic-crosslinking method, with GEN-CS as the carrier material and sodium tripolyphosphate (TPP) as the crosslinking agent. As a result, TAM-GEN-CS-NPs exhibited a spherical morphology with an average size of 299.8 nm. The encapsulation efficiency and drug loading content were 85.77% and 14.13 µg/mg, respectively. Compared with free TAM, TAM-GEN-CS-NPs displayed obvious slow-release performance. In vitro cellular assays demonstrated that TAM-GEN-CS-NPs had active targeting and proliferation inhibitory effects on MCF-7 cells. The IC50 of TAM and TAM-GEN-CS-NPs were 10.25 µg/mL and 7.22 µg/mL, respectively. More importantly, the combination index (CI) value of TAM and GEN was less than 1, indicating synergistic effects. Therefore, TAM-GEN-CS-NPs hold the potential to enhance TAM therapy for breast cancer through active targeting and synergistic treatment strategies.

The F-box protein OsFBX156 positively regulates rice defence against the blast fungus Magnaporthe oryzae by mediating ubiquitination-dependent degradation of OsHSP71.1.

F-box protein is a subunit of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which plays a critical role in regulating different pathways in plant immunity. In this study, we identified the rice (Oryza sativa) F-box protein OsFBX156, which targets the heat shock protein 70 (OsHSP71.1) to regulate resistance to the rice blast fungus Magnaporthe oryzae. Overexpression of OsFBX156 or knockout of OsHSP71.1 in rice resulted in the elevation of pathogenesis-related (PR) genes and an induction burst of reactive oxygen species (ROS) after flg22 and chitin treatments, thereby enhancing resistance to M. oryzae. Furthermore, OsFBX156 can promote the degradation of OsHSP71.1 through the 26S proteasome pathway. This study sheds lights on a novel mechanism wherein the F-box protein OsFBX156 targets OsHSP71.1 for degradation to promote ROS production and PR gene expression, thereby positively regulating rice innate immunity.

Network pharmacology combined with experimental validation to investigate the effect of Rongjin Niantong Fang on chondrocyte apoptosis in knee osteoarthritis.

Knee osteoarthritis (KOA) is a chronic degenerative disease that affects the quality of life of middle­aged and elderly individuals, and is one of the major factors leading to disability. Rongjin Niantong Fang (RJNTF) can alleviate the clinical symptoms of patients with KOA, but the molecular mechanism underlying its beneficial effects on KOA remains unknown. Using pharmacological analysis and in vitro experiments, the active components of RJNTF were analyzed to explore their potential therapeutic targets and mechanisms in KOA. The potential targets and core signaling pathways by which RJNTF exerts its effects on KOA were obtained from databases such as Gene Expression Omnibus, Traditional Chinese Medicine Systems Pharmacology and Analysis Platform. Subsequently, chondrocyte apoptosis was modeled using hydrogen peroxide (H2O2). Cell Counting Kit­8 assay involving a poly [ADP­ribose] polymerase­1 (PARP1) inhibitor, DAPI staining, reverse transcription­quantitative PCR, Annexin V­FITC/PI staining and flow cytometry, western blotting and co­immunoprecipitation analysis were used to determine the therapeutic efficacy of RJNTF on KOA and to uncover the molecular mechanism. It was found that PARP1­knockdown lentivirus, incubation with PARP1 inhibitor PJ34, medium and high doses of RJNTF significantly reduced H2O2­induced chondrocyte apoptosis. Medium and high doses of RJNTF downregulated the expression of cleaved caspase­3, cleaved PARP1 and PAR total proteins, as well as nucleus proteins of apoptosis­inducing factor (AIF) and migration inhibitory factor (MIF), and upregulated the expression of caspase­3, PARP1 total protein, as well as the cytoplasmic expression of AIF and MIF, suggesting that RJNTF may inhibit chondrocyte apoptosis through the PARP1/AIF signaling pathway.

Antagonistic control of rice immunity against distinct pathogens by the two transcription modules via salicylic acid and jasmonic acid pathways.

Although the antagonistic effects of host resistance against biotrophic and necrotrophic pathogens have been documented in various plants, the underlying mechanisms are unknown. Here, we investigated the antagonistic resistance mediated by the transcription factor ETHYLENE-INSENSITIVE3-LIKE 3 (OsEIL3) in rice. The Oseil3 mutant confers enhanced resistance to the necrotroph Rhizoctonia solani but greater susceptibility to the hemibiotroph Magnaporthe oryzae and biotroph Xanthomonas oryzae pv. oryzae. OsEIL3 directly activates OsERF040 transcription while repressing OsWRKY28 transcription. The infection of R. solani and M. oryzae or Xoo influences the extent of binding of OsEIL3 to OsWRKY28 and OsERF040 promoters, resulting in the repression or activation of both salicylic acid (SA)- and jasmonic acid (JA)-dependent pathways and enhanced susceptibility or resistance, respectively. These results demonstrate that the distinct effects of plant immunity to different pathogen types are determined by two transcription factor modules that control transcriptional reprogramming and the SA and JA pathways.

Integration of Metabolomic and Transcriptomic Analyses Reveals the Molecular Mechanisms of Flower Color Formation in Prunus mume.

Flower color is an important trait that affects the economic value of Prunus mume, a famous ornamental plant in the Rosaceae family. P. mume with purple-red flowers is uniquely charming and highly favored in landscape applications. However, little is known about its flower coloring mechanism, which stands as a critical obstacle on the path to innovative breeding for P. mume flower color. In this study, transcriptomic and targeted metabolomic analyses of purple-red P. mume and white P. mume were performed to elucidate the mechanism of flower color formation. In addition, the expression patterns of key genes were analyzed using an RT-qPCR experiment. The results showed that the differential metabolites were significantly enriched in the flavonoid synthesis pathway. A total of 14 anthocyanins emerged as the pivotal metabolites responsible for the differences in flower color between the two P. mume cultivars, comprising seven cyanidin derivatives, five pelargonium derivatives, and two paeoniflorin derivatives. Moreover, the results clarified that the metabolic pathway determining flower color in purple-red P. mume encompasses two distinct branches: cyanidin and pelargonidin, excluding the delphinidin branch. Additionally, through the integrated analysis of transcriptomic and metabolomic data, we identified 18 key genes responsible for anthocyanin regulation, thereby constructing the gene regulatory network for P. mume anthocyanin synthesis. Among them, ten genes (PmCHI, PmGT2, PmGT5, PmGST3, PmMYB17, PmMYB22, PmMYB23, PmbHLH4, PmbHLH10, and PmbHLH20) related to anthocyanin synthesis were significantly positively correlated with anthocyanin contents, indicating that they may be the key contributors to anthocyanin accumulation. Our investigation contributes a novel perspective to understanding the mechanisms responsible for flower color formation in P. mume. The findings of this study introduce novel strategies for molecular design breeding aimed at manipulating flower color in P. mume.

Strategies to attenuate ciprofloxacin inhibition on enhanced biological phosphorus removal from wastewater and its recoverability.

The inhibiting effects of ciprofloxacin (CIP) on enhanced biological phosphorus removal (EBPR) were investigated with no change in reactor operation and with increased aeration rate and sludge retention time (SRT) to explore inhibition-alleviating solutions. Additionally, performance recoverability was evaluated. The results showed that the phosphorus removal efficiency in the presence of 0.002-0.092 mg/L CIP for 7 days was only 12.5%. Increasing the aeration rate relieved inhibition (33.5% phosphorus removal efficiency on Day 7), and increasing SRT slowed EBPR performance deterioration. The EBPR performance recovered from CIP inhibition and increases in the aeration rate and SRT resulted in different recovery phenomena. The maximum PO43--P release rate continued to decrease in the first 2 days of the recovery stage and then gradually increased. However, the maximum PO43--P uptake rate immediately increased at different rates among reactors, which might be attributed to variations in the microbial community structure, decreased poly-P content, and enhanced abundances of ABC transporters and quorum sensing. It was found that some microorganisms associated with phosphorus removal were more tolerant to CIP than glycogen accumulating organisms. Moreover, the increased relative abundance of the qepA gene indicated that the microorganisms in the EBPR system had strong antibiotic resistance capacity. The bacterial community structure was significantly affected by CIP and could not recover to the initial structure. The results help to provide technical support for the operation of the EBPR process in the presence of CIP and to increase the understanding of system recoverability.

Trivalent Nickel-Catalyzing Electroconversion of Alcohols to Carboxylic Acids.

The comprehension of activity and selectivity origins of the electrooxidation of organics is a crucial knot for the development of a highly efficient energy conversion system that can produce value-added chemicals on both the anode and cathode. Here, we find that the potential-retaining trivalent nickel in NiOOH (Fermi level, -7.4 eV) is capable of selectively oxidizing various primary alcohols to carboxylic acids through a nucleophilic attack and nonredox electron transfer process. This nonredox trivalent nickel is highly efficient in oxidizing primary alcohols (methanol, ethanol, propanol, butanol, and benzyl alcohol) that are equipped with the appropriate highest occupied molecular orbital (HOMO) levels (-7.1 to -6.5 eV vs vacuum level) and the negative dual local softness values (Δsk, -0.50 to -0.19) of nucleophilic atoms in nucleophilic hydroxyl functional groups. However, the carboxylic acid products exhibit a deeper HOMO level (<-7.4 eV) or a positive Δsk, suggesting that they are highly stable and weakly nucleophilic on NiOOH. The combination (HOMO, Δsk) is useful in explaining the activity and selectivity origins of electrochemically oxidizing alcohols to carboxylic acid. Our findings are valuable in creating efficient energy conversions to generate value-added chemicals on dual electrodes.

The relationship between nonsteroidal anti-inflammatory drugs and cancer incidence: An umbrella review.

Several clinical and preclinical studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, reduce the incidence of various cancer types. However, there is still a lack of literature evaluating the overall association between multiple cancer morbidities and NSAIDs. Thus, we conducted an umbrella review to evaluate the quality of evidence, validity, and biases of the existing systematic reviews and meta-analyses on the relationships between NSAIDS and multiple tumor incidence outcomes. We found that NSAIDs might be associated with a decreased risk of several cancers, including the central nervous system, breast, esophageal, gastric, head and neck, hepatocellular, cholangiocarcinoma, colorectal, endometrial, lung, ovary, prostate, and pancreatic cancers, but regular intake of any dose of non-aspirin NSAIDs (NA-NSAIDs) could increase the incidence of kidney cancer. However, most of included studies are evaluated as low quality according to our evidence assessment. Furthermore, due to the potential side effects, such as hemorrhage, digestive symptoms and peptic ulcer, it is still not recommend to use NSAIDs regularly to prevent cancers.

Biodegradable Nanoflowers with Abaloparatide Spatiotemporal Management of Functional Alveolar Bone Regeneration.

Post-extraction alveolar bone atrophy greatly hinders the subsequent orthodontic tooth movement (OTM) or implant placement. In this study, we synthesized biodegradable bifunctional bioactive calcium phosphorus nanoflowers (NFs) loaded with abaloparatide (ABL), namely ABL@NFs, to achieve spatiotemporal management for alveolar bone regeneration. The NFs exhibited a porous hierarchical structure, high drug encapsulation efficacy, and desirable biocompatibility. ABL was initially released to recruit stem cells, followed by sustained release of Ca2+ and PO43- for in situ interface mineralization, establishing an osteogenic "biomineralized environment". ABL@NFs successfully restored morphologically and functionally active alveolar bone without affecting OTM. In conclusion, the ABL@NFs demonstrated promising outcomes for bone regeneration under orthodontic condition, which might provide a desirable reference of man-made "bone powder" in the hard tissue regeneration field.

Variation in the physiological response of adult worker bees of different ages (Apis mellifera L.) to pyraclostrobin stress.

The social division of labor within the honeybee colony is closely related to the age of the bees, and the age structure is essential to the development and survival of the colony. Differences in tolerance to pesticides and other external stresses among worker bees of different ages may be related to their social division of labor and corresponding physiological states. Pyraclostrobin was widely used to control the fungal diseases of nectar and pollen plants, though it was not friend to honey bees and other pollinators. This work aimed to determine the effects of field recommended concentrations of pyraclostrobin on the activities of protective and detoxifying enzymes, on the expression of genes involved in nutrient metabolism, and immune response in worker bees of different ages determined to investigate the physiological and biochemical differences in sensitivity to pyraclostrobin among different age of worker bees. The result demonstrates that the tolerance of adult worker bees to pyraclostrobin was negatively correlated with their age, and the significantly reduced survival rate of forager bees (21 day-old) with continued fungicide exposure. The activities of protective enzymes (CAT and SOD) and detoxifying enzymes (CarE, GSTs and CYP450) in different ages of adult worker bees were significantly altered, indicating the physiological response and the regulatory capacity of worker bees of different ages to fungicide stress was variation. Compared with 1 and 8 day-old worker bees, the expression of nutrient-related genes (ilp1 and ilp2) and immunity-related genes (apidaecin and defensin1) in forager bees (21 day-old) was gradually downregulated with increasing pyraclostrobin concentrations. Moreover, the expression of vitellogenin and hymenoptaecin in forager bees (21 day-old) was also decreased in high concentration treatment groups (250 and 313 mg/L). The present study confirmed the findings of the chronic toxicity of pyraclostrobin on the physiology and biochemistry of worker bees of different ages, especially to forager bees (21 day-old). These results would provide important physiological and biochemical insight for better understanding the potential risks of pyraclostrobin on honeybees and other non-target pollinators.

Macroscopic assembly of 2D materials for energy storage and seawater desalination.

Since the discovery of graphene in 2004, two-dimensional (2D) materials have attracted widespread attention due to their excellent physical and chemical properties in the fields of energy, environment, catalysis, and optoelectronics. However, there are still many key problems in the process of practical application. To further promote the potential of 2D materials for practical applications, macroscopic assembly of 2D materials is crucial for the continued development of 2D materials, especially in the fields of energy storage and seawater desalination. Therefore, this review focuses on the latest progress and current status related to the macroscopic assembly of 2D materials, including 1D fibers, 2D films, and 3D architectures. In addition, the application of macroscopic bodies assembled based on 2D materials in the fields of energy storage and seawater desalination is also introduced. Finally, future directions for the macroscopic assembly of 2D materials and their applications are prospected.

Nonredox trivalent nickel catalyzing nucleophilic electrooxidation of organics.

A thorough comprehension of the mechanism behind organic electrooxidation is crucial for the development of efficient energy conversion technology. Here, we find that trivalent nickel is capable of oxidizing organics through a nucleophilic attack and electron transfer via a nonredox process. This nonredox trivalent nickel exhibits exceptional kinetic efficiency in oxidizing organics that possess the highest occupied molecular orbital energy levels ranging from -7.4 to -6 eV (vs. Vacuum level) and the dual local softness values of nucleophilic atoms in nucleophilic functional groups, such as hydroxyls (methanol, ethanol, benzyl alcohol), carbonyls (formamide, urea, formaldehyde, glucose, and N-acetyl glucosamine), and aminos (benzylamine), ranging from -0.65 to -0.15. The rapid electrooxidation kinetics can be attributed to the isoenergetic channels created by the nucleophilic attack and the nonredox electron transfer via the unoccupied eg orbitals of trivalent nickel (t2g6eg1). Our findings are valuable in identifying kinetically fast organic electrooxidation on nonredox catalysts for efficient energy conversions.

LncRNA SLC1A5-AS/MZF1/ASCT2 Axis Contributes to Malignant Progression of Hepatocellular Carcinoma.

BACKGROUND: Hypoxia is a pivotal factor influencing cellular gene expression and contributing to the malignant progression of tumors. Metabolic anomalies under hypoxic conditions are predominantly mediated by mitochondria. Nonetheless, the exploration of hypoxia-induced long noncoding RNAs (lncRNAs) associated with mitochondria remains largely uncharted. METHODS: We established hypoxia cell models using primary human hepatocytes (PHH) and hepatocellular carcinoma (HCC) cell lines. We isolated mitochondria for high-throughput sequencing to investigate the roles of candidate lncRNAs in HCC progression. We employed in vitro and in vivo assays to evaluate the functions of solute carrier family 1 member 5 antisense lncRNA (SLC1A5-AS). RNA-seq was utilized to scrutinize the comprehensive genome profile regulated by SLC1A5-AS in HCC. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were utilized to validate the expression of alanine-serine-cysteine transporter 2 (ASCT2, encoded by the SLC1A5 gene), and a glutamine uptake assay was employed to estimate the glutamine uptake capacity of Huh-7 cells after SLC1A5-AS overexpression. To delve into the mechanisms governing the regulation of SLC1A5 expression by SLC1A5-AS, we employed a biotin-labeled SLC1A5-AS probe in conjunction with a western blot assay to confirm the interactions between SLC1A5-AS and candidate transcription factors. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were utilized to authenticate the effects of the predicted transcription factors on SLC1A5 promoter activity. RESULTS: Following the screening, we identified CTB-147N14.6, derived from the antisense strand of the SLC1A5 gene, which we have named SLC1A5-AS. SLC1A5-AS exhibited significantly elevated expression levels in HCC tissue and was associated with poor prognosis in HCC patients. In vitro and in vivo assays revealed that the overexpression of SLC1A5-AS significantly heightened cell invasion and metastasis. RNA-seq data unveiled SLC1A5-AS involvement in glutamine metabolism, left-handed amino (L-amino) acid transmembrane transporter activity, and the nuclear factor kappa-B (NF-κB) signaling pathway. Overexpression of SLC1A5-AS markedly increased ASCT2 mRNA/protein levels, thereby enhancing glutamine uptake and promoting the growth and metastasis of HCC cells. Mechanistically, higher RNA levels of SLC1A5-AS directly bound with myeloid zinc finger 1 (MZF1), acting as a transcriptional repressor, thus diminishing its binding to the SLC1A5 promoter region. CONCLUSIONS: Our findings unveil a novel role for the lncRNA SLC1A5-AS in glutamine metabolism, suggesting that targeting SLC1A5-AS/MZF1, in conjunction with ASCT2 inhibitor treatment, could be a potential therapeutic strategy for this disease.

Facile one-step synthesis of mesoporous Pt-based alloy nanospheres for ethanol electrooxidation.

Mesoporous Pt-based alloy nanospheres were prepared via a one-step soft-template strategy. The regulation of electronic structure, lattice contraction and abundant active sites endowed the mesoporous Pt-based catalysts with remarkable electrochemical activity towards ethanol oxidation reaction.

Harnessing nanobodies to expand the recognition spectrum of plant NLRs for diverse pathogens.

The strategy to expand the recognition spectrum of plant nucleotide-binding domain leucine-rich repeat (NLR) proteins by modifying their recognition sequences is generally limited and often unsuccessful. Kourelis et al. introduced a groundbreaking approach for generating a customized immune receptor, called Pikobody. This method involves integrating a nanobody domain of a fluorescent protein (FP) into a plant NLR. Their research demonstrates that the resulting Pikobody successfully initiates an immune response against diverse pathogens when exposed to the corresponding FP.

The rice peroxisomal receptor PEX5 negatively regulates resistance to rice blast fungus Magnaporthe oryzae.

The receptor protein PEX5, an important component of peroxisomes, regulates growth, development, and immunity in yeast and mammals. PEX5 also influences growth and development in plants, but whether it participates in plant immunity has remained unclear. Here, we report that knockdown of OsPEX5 enhances resistance to the rice blast fungus Magnaporthe oryzae. We demonstrate that OsPEX5 interacts with the E3 ubiquitin ligase APIP6, a positive regulator of plant immunity. APIP6 ubiquitinates OsPEX5 in vitro and promotes its degradation in vivo via the 26S proteasome pathway. In addition, OsPEX5 interacts with the aldehyde dehydrogenase OsALDH2B1, which functions in growth-defense trade-offs in rice. OsPEX5 stabilizes OsALDH2B1 to enhance its repression of the defense-related gene OsAOS2. Our study thus uncovers a previously unrecognized hierarchical regulatory mechanism in which an E3 ubiquitin ligase targets a peroxisome receptor protein that negatively regulates immunity in rice by stabilizing an aldehyde dehydrogenase that suppresses defense gene expression.