Resilience evaluation of low-carbon supply chain based on improved matter-element extension model.

How to evaluate the resilience level and change trend of supply chain is an important research direction in current supply chain management practice. This paper proposes a new method of supply chain resilience assessment based on hesitant fuzzy linguistic term set (HFLTS) and matter element extension theory. Firstly, based on the research status quo at home and abroad, a low-carbon enterprise supply chain resilience assessment index system is established, which includes six first-level indicators and corresponding 21 second-level indicators of product supply resilience, resource resilience, partner resilience, information response resilience, financial resilience and knowledge resilience. Secondly, HFLTS was used to collect expert opinions and Ordered Weighted Arithmetic (OWA) to calculate the expert composite language, by which the fuzzy evaluation matrix of supply chain resilience assessment indicators was obtained. Once again, the resilience indicator weights are determined based on a game-theoretic portfolio assignment method combining the best-worst method (BWM) and the CRITIC method. Finally, the nearness degree function is combined with the extension comprehensive evaluation method to improve the matter element extension model, and the supply chain resilience assessment model of low-carbon enterprises based on the game theory combination assignment-improved matter element extension is established. Taking X low-carbon enterprise as an example, the evaluation results show that the supply chain resilience level of this enterprise is II, and the eigenvalue of the grade variable is 2.69, and the supply chain resilience is shifting to III, and the supply chain resilience is shifting to III, which indicates that the supply chain resilience of this enterprise is being enhanced. Therefore, the improved matter element extension not only ensures the accuracy of the evaluation results, but also has higher prediction accuracy.

Silver Nanoparticles In Situ Enhanced Electrochemiluminescence of the Porphyrin Organic Matrix for Highly Sensitive and Rapid Monitoring of Tetracycline Residues.

Accurate monitoring of tetracycline (TC) residues in the environment is crucial for avoiding contaminant risk. Herein, a novel TC biosensor was facilely designed by integrating silver nanoparticles (Ag NPs) into the porphyrin metal-organic matrix (Ag@AgPOM) as a bifunctional electrochemiluminescence (ECL) probe. Different from the step-by-step synthesis of the co-reaction accelerator and ECL emitter, the co-reaction accelerators Ag NPs were in situ-grown on the surface of 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) via a simple one-pot approach. Symbiotic Ag NPs on Ag@AgPOM formed an intimate interface and increased the collision efficiency of the ECL reaction, achieving the ECL enhancement of TCPP. Under the optimized conditions, the ternary ECL biosensor showed a wide linear detection range toward TC with a low detection limit of 0.14 fmol L-1. Compared with the traditional HPLC and ELISA methods, satisfied analytical adaptability made this sensing strategy feasible to monitor TC in complex environmental samples.

Embracing ChatGPT for Medical Education: Exploring Its Impact on Doctors and Medical Students.

ChatGPT (OpenAI), a cutting-edge natural language processing model, holds immense promise for revolutionizing medical education. With its remarkable performance in language-related tasks, ChatGPT offers personalized and efficient learning experiences for medical students and doctors. Through training, it enhances clinical reasoning and decision-making skills, leading to improved case analysis and diagnosis. The model facilitates simulated dialogues, intelligent tutoring, and automated question-answering, enabling the practical application of medical knowledge. However, integrating ChatGPT into medical education raises ethical and legal concerns. Safeguarding patient data and adhering to data protection regulations are critical. Transparent communication with students, physicians, and patients is essential to ensure their understanding of the technology's purpose and implications, as well as the potential risks and benefits. Maintaining a balance between personalized learning and face-to-face interactions is crucial to avoid hindering critical thinking and communication skills. Despite challenges, ChatGPT offers transformative opportunities. Integrating it with problem-based learning, team-based learning, and case-based learning methodologies can further enhance medical education. With proper regulation and supervision, ChatGPT can contribute to a well-rounded learning environment, nurturing skilled and knowledgeable medical professionals ready to tackle health care challenges. By emphasizing ethical considerations and human-centric approaches, ChatGPT's potential can be fully harnessed in medical education, benefiting both students and patients alike.

Changes in clinical parameters and inflammatory markers after blood culture collection facilitate early identification of positive culture in adult patients with COVID-19 and clinically suspected bloodstream infection.

OBJECTIVE: We explored whether changes in clinical parameters and inflammatory markers can facilitate early identification of positive blood culture in adult patients with COVID-19 and clinically suspected bloodstream infection (BSI). METHODS: This single-center retrospective study enrolled 20 adult patients with COVID-19 admitted to the intensive care unit who underwent blood culture for clinically suspected BSI (February 2020-November 2021). We divided patients into positive (Pos) and negative blood culture groups. Clinical parameters and inflammatory markers were obtained from medical records between blood culture collection and the first positive or negative result and compared between groups on different days. RESULTS: Patients in the positive culture group had significantly older age and higher D-dimer, immunoglobulin 6 (IL-6), and Sequential Organ Failure Assessment score as well as lower albumin (ALB). The area under the receiver operating characteristic curve (AUC) was 0.865 for IL-6, D-dimer and ALB on the first day after blood culture collection; the AUC was 0.979 for IL-6, IL-10, D-dimer, and C-reactive protein on the second day after blood culture collection. CONCLUSION: Changes in clinical parameters and inflammatory markers after blood culture collection may facilitate early identification of positive culture in adult patients with COVID-19 and clinically suspected BSI.

Clinical Use of Tranexamic Acid in High Tibial Osteotomy: A Systematic Review and Meta-analysis.

Background: High tibial osteotomy (HTO) can cause postoperative hemorrhage. The use of tranexamic acid to reduce the hemorrhage is still controversial. Purpose: To investigate the efficacy and safety of tranexamic acid in HTO. Study Design: Systematic review; Level of evidence, 4. Methods: Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the authors conducted a comprehensive search of the Embase, Cochrane Library, PubMed, Web of Science, MEDLINE, and Foreign Medical Literature Retrieval Service databases between their inception and January 1, 2023. All clinical studies comparing the use of tranexamic acid versus no tranexamic acid during HTO were collected. The primary outcome measures were hemoglobin decrease, drainage volume, and blood loss, and the secondary outcome measures were wound complications, blood transfusion, and postoperative thrombosis. All indicators were analyzed using meta-analysis software. Results were reported as mean differences or risk ratios with 95% confidence intervals. Results: Of 152 initial results, 9 studies involving 908 patients were included. The tranexamic acid group had lower indicators for total blood loss, hemoglobin decrease, and total drainage volume (P < .00001 for all). There were no differences between patients with versus without tranexamic acid in wound complications, including hematoma (P = .21) or infection (P = .18), nor were there any group differences in the prevalence of blood transfusion (P = .21) or postoperative thrombosis (P = .36). Conclusion: Tranexamic acid was able to effectively reduce postoperative hemorrhage in patients undergoing HTO without affecting the rates of wound complications, blood transfusion, or postoperative thrombosis.

Non-destructive detection of single corn seed vigor based on visible/near-infrared spatially resolved spectroscopy combined with chemometrics.

Seed vigor is an essential quality evaluation index for seed selection. However, accurately detecting the vigor of a single corn seed is challenging. In this study, we constructed a single-fiber spatially resolved detection device using visible/near-infrared spectroscopy to investigate the patterns and correlations between spatially resolved spectroscopy (SRS) at 500-1000 nm and seed vigor. The device collected spectral data at a light source-detector distance of 5-6.6 mm on the embryo side (S1) and endosperm side (S2) of the corn seeds. The proposed spectral ratio method based on SRS and spectral combination analysis achieved an improvement in the detection accuracy of different corn seed vigor. Modeling by SG-CARS-PLSDA using the ratio method showed further improvement in the prediction ability. The highest accuracy for both S1 and S2 in the Zhengdan 958 variety was 91.67 %, while those of S1 and S2 for the Shaandan 650 variety were 86.67 % and 88.33 %, respectively. In addition, SRS was found to be more advantageous in S2 acquisition, verifying the potential of SRS in the non-destructive testing of seed vigor. This provides a favorable reference for the comprehensive evaluation of other internal quality indices of seeds.

Predictive and Prognostic Potentials of Lymphocyte-C-Reactive Protein Ratio Upon Hospitalization in Adult Patients with Acute Pancreatitis.

Purpose: In this study, our objective was to investigate the potential utility of lymphocyte-C-reactive protein ratio (LCR) as a predictor of disease progression and a screening tool for intensive care unit (ICU) admission in adult patients with acute pancreatitis (AP). Methods: We included a total of 217 adult patients with AP who were admitted to the First Affiliated Hospital of Harbin Medical University between July 2019 and June 2022. These patients were categorized into three groups: mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), based on the presence and duration of organ dysfunction. Various demographic and clinical data were collected and compared among different disease severity groups. Results: Height, diabetes, lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet count (PLT), D-Dimer, albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), glucose (GLU), calcium ion (Ca2+), C-reactive protein (CRP), procalcitonin (PCT), hospitalization duration, ICU admission, need for BP, LCR, sequential organ failure assessment (SOFA) score, bedside index for severity in AP (BISAP) score, and modified Marshall score showed significant differences across different disease severity groups upon hospitalization. Notably, there were significant differences in LCR between the MAP group and the MSAP and SAP combined group, and the MAP and MSAP combined group and the SAP group, and adult AP patients with ICU admission and those without ICU admission upon hospitalization. Conclusion: In summary, LCR upon hospitalization can be utilized as a simple and reliable predictor of disease progression and a screening tool for ICU admission in adult patients with AP.

Dynamic lymphocyte-CRP ratio as a predictor: a single-centre retrospective study on disease severity and progression in adult COVID-19 patients.

OBJECTIVE: To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). METHODS: This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. RESULTS: This study included 145 patients assigned to moderate (n = 105), severe (n = 33) and critical groups (n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of -0.564, -0.548, -0.550 and -0.429 at four different times. CONCLUSION: Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.

Transformation risk and associated survival outcome of marginal zone lymphoma: A nationwide study.

Histological transformation into an aggressive B-cell lymphoma indicates a poor survival outcome for patients with indolent marginal zone lymphoma (MZL), which has been less studied. Large-scale data with long-term follow-up to investigate MZL transformation is limited. Here, by reporting a US-Nationwide cohort of 30,619 MZL patients diagnosed between 2000 and 2019, we found that transformation occurred in 2.08% (N = 624) of MZL cases, with the transformation incidence of 3.1 per 1,000 person-years. Advanced Ann Arbor stage, nodal MZL (NMZL) and splenic MZL (SMZL) were associated with an elevated risk of transformation. Certain subtype-specific characteristics, such as non-gastric extra-nodal MZL (vs. gastric, HR, 1.51, 95%CI 1.13-2.04; p = 0.006), and receiving splenectomy for SMZL (HR, 2.04, 95%CI 1.28-3.26; p = 0.003), also indicated a higher risk of transformation. Besides, transformation independently increased the overall mortality risk (HR, 1.38, 95%CI 1.24-1.53, p < 0.001), especially the higher lymphoma-caused mortality risk (HR, 3.21, 95%CI 2.81-3.67, p < 0.001). Transformation was also associated with a higher percentage of lymphoma-caused deaths. The post-transformation prognostic analyses demonstrated that female gender and age ≥ 65 years independently affected patients' mortalities. These findings, based on the largest cohort to date, contribute to a better understanding of transformed MZL, and provide valuable reference points for guidelines and patient counseling.

Binary-amplifying electrochemiluminescence sensor for sensitive assay of catechol and luteolin based on HKUST-1 derived CuO nanoneedles as a novel luminophore.

Herein, a highly novel and effective electrochemiluminescence (ECL) sensor based on metal-organic framework (MOF, HKUST-1) derived CuO nanoneedles (HKUST-1 derived CuO NNs), gold nanoparticles (AuNPs) and TiO2 was developed for ultrasensitive detection of catechol and luteolin. The HKUST-1 derived CuO NNs were employed as luminophore for the first time, which were successfully fabricated by using HKUST-1 as precursor. The results revealed that the HKUST-1 derived CuO NNs exhibit excellent ECL activity ascribed to its abundant active site and the high specific surface area, thus obviously promoting the separation and transfer of charge and further improving the current density of ECL sensor. To binary-amplify the signal of the ECL sensor, the AuNPs and TiO2 nano-materials with good biocompatibility, great electron transport efficiency and high catalytic activity were used as co-reaction accelerators in the ECL process. Dependent on the above brilliant strategy, the proposed ECL sensor achieved wide linear ranges from 3 × 10-9 - 1 × 10-4 M for catechol and 1 × 10-8 - 2 × 10-4 M for luteolin, with the detection limits of 1.5 × 10-9 M for catechol and 5.3 × 10-9 M for luteolin, respectively. Furthermore, the ECL sensor exhibited outstanding selectivity, repeatability, stability and obtained great feedback on determination of catechol and luteolin in actual samples. The method not only filled a gap in the ECL application of MOF-derived materials but also provided a novel sight for design other highly efficient luminescent materials.

Inhibition of Endoplasmic Reticulum Stress Improves Chronic Ischemic Hippocampal Damage Associated with Suppression of IRE1α/TRAF2/ASK1/JNK-Dependent Apoptosis.

Chronic cerebral ischemia is a complex form of stress, of which the most common hemodynamic characteristic is chronic cerebral hypoperfusion (CCH). Lasting endoplasmic reticulum (ER) stress can drive neurological disorders. Targeting ER stress shows potential neuroprotective effects against stroke. However, the role of ER stress in CCH pathological processes and the effects of targeting ER stress on brain ischemia are unclear. Here, a CCH rat model was established by bilateral common carotid artery occlusion. Rats were treated with 4-PBA, URB597, or both for 4 weeks. Neuronal morphological damage was detected using hematoxylin-eosin staining. The expression levels of the ER stress-ASK1 cascade-related proteins GRP78, IRE1α, TRAF2, CHOP, Caspase-12, ASK1, p-ASK1, JNK, and p-JNK were assessed by Western blot. The mRNA levels of TNF-α, IL-1ß, and iNOS were assessed by RT-PCR. For oxygen-glucose deprivation experiments, mouse hippocampal HT22 neurons were used. Apoptosis of the hippocampus and HT22 cells was detected by TUNEL staining and Annexin V-FITC analysis, respectively. CCH evoked ER stress with increased expression of GRP78, IRE1α, TRAF2, CHOP, and Caspase-12. Co-immunoprecipitation experiments confirmed the interaction between TRAF2 and ASK1. ASK1/JNK signaling, inflammatory cytokines, and neuronal apoptosis were enhanced, accompanied by persistent ER stress; these were reversed by 4-PBA and URB597. Furthermore, the ASK1 inhibitor GS4997 and 4-PBA displayed synergistic anti-apoptotic effects in cells with oxygen-glucose deprivation. In summary, ER stress-induced apoptosis in CCH is associated with the IRE1α/TRAF2/ASK1/JNK signaling pathway. Targeting the ER stress-ASK1 cascade could be a novel therapeutic approach for ischemic cerebrovascular diseases.

Compassionate use of contezolid in a toddler with severe community-acquired pneumonia induced by staphylococcus aureus: a case report and follow-up.

Background: Initial choices of antimicrobial therapy for most cases of community-acquired pneumonia (CAP) in children under 5 years of age are typically based on local epidemiology, risk factors assessment, and subsequent clinical parameters and positive cultures, which can lead to the underdiagnosis and underestimation of lung infections caused by uncommon pathogens. Contezolid, an orally administered oxazolidinone antibiotic, gained approval from the National Medical Products Administration (NMPA) of China in June 2021 for managing complicated skin and soft tissue infections (cSSTI) caused by staphylococcus aureus (SA), streptococcus pyogenes, or streptococcus agalactis. Owing to its enhanced safety profile and ongoing clinical progress, the scope of contezolid's clinical application continues to expand, benefiting a growing number of patients with Gram-positive bacterial infections. Case summary: In this report, we present the first use of contezolid in a toddler with severe CAP caused by SA, aiming to avoid potential adverse drug reactions (ADRs) associated with vancomycin and linezolid. Conclusion: Although contezolid has not been officially indicated for CAP, it has been shown to be effective and safe in the management of SA-induced severe CAP in this toddler, suggesting its potential as an alternative option in the dilemma, especially for patients who are susceptible or intolerant to ADRs associated with first-line anti-methicillin-resistant staphylococcus aureus (MRSA) antimicrobial agents.

[A new benzopyran glycoside from Gentiana macrophylla].

Thirteen compounds were isolated and identified from 70% ethanol extract of the roots of Gentiana macrophylla by multi-chromatographic methods, including microporous resin, silica gel, and C_(18) reversed-phase column chromatography, as well as HPLC as follows: macrophylloside G(1), macrophylloside D(2), 5-formyl-2,3-dihydroisocoumarin(3),(+)-medicarpin(4),(+)-syringaresinol(5), liquiritigenin(6),(3R)-sativanone(7),(3R)-3'-O-methylviolanone(8), 4,2',4'-trihydroxychalcone(9), latifolin(10), gentioxepine(11), 6α-hydroxycyclonerolidol(12), and ethyl linoleate(13). Compound 1 was a new benzopyran glycoside. Compounds 4, 6-10, 12, and 13 were isolated for the first time from Gentiana plants. Compounds 1 and 2 showed promising hepatoprotective activity against D-GalN-induced AML12 cell damage at the concentration of 10 µmol·L~(-1), and compound 2 exhibited more significant activity than silybin at the same concentration.

Interfacial Regulation toward Efficient CsPbBr3 Quantum Dot-Based Inverted Perovskite Light-Emitting Diodes.

Inverted perovskite light-emitting diodes (PeLEDs) based on quantum dots (QDs) are some of the most promising candidates for next-generation lighting and display applications. Due to the strong fluorescence quenching caused by zinc oxide, high performance in such inverted devices remains challenging. Here, we report an efficient inverted green CsPbBr3 QDs LED using an emitting buffer layer. Ultrathin CsPbBr3 QD emitters act as the buffer layer to reduce the interface luminescence quenching reaction at the ZnO/upper emitting layer interface, increasing the probability of exciton recombination within the emissive layer and regulating the charge transport, leading to effective carrier recombination. The resulting device exhibits an external quantum efficiency of 13.1%, enhanced by about 4.7 times compared with that without a buffer layer device. This work provides a path to fabricating high-performance inverted PeLEDs.

Curcumin Changed the Number, Particle Size, and miRNA Profile of Serum Exosomes in Roman Laying Hens under Heat Stress.

Exosomes have the ability to transport RNA/miRNAs and possess immune modulatory functions. Heat stress, a significant limiting factor in the poultry industry, can induce oxidative stress and suppress the immune responses of laying hens. In this study, we investigated the expression profiles of serum exosomes and their miRNAs in Roman laying hens who were fed a diet with either 0 or 200 mg/kg curcumin under heat stress conditions. The numbers of exosomes were significantly higher in both the HC (heat stress) and HT (heat stress with 200 mg/kg curcumin) groups compared to the NC (control) group and NT (control with 200 mg/kg curcumin) group (p < 0.05). Additionally, we observed that the most prevalent particle diameters were 68.75 nm, 68.25 nm, 54.25 nm, and 60.25 nm in the NC, NT, HC, and HT groups, respectively. From our sRNA library analysis, we identified a total of 863 unique miRNAs; among them, we screened out for subsequent bioinformatics analysis a total of 328 gga-miRNAs(chicken miRNA from the miRbase database). The KEGG pathways that are associated with target genes which are regulated by differentially expressed miRNAs across all four groups at a p-value < 0.01 included oxidative phosphorylation, protein export, cysteine and methionine metabolism, fatty acid degradation, ubiquitin-mediated proteolysis, and cardiac muscle contraction. The above findings suggest that curcumin could mitigate heat-induced effects on laying hens by altering the miRNA expression profiles of serum exosomes along with related regulatory pathways.

Rare and complex diseases in focus: ChatGPT's role in improving diagnosis and treatment.

Rare and complex diseases pose significant challenges to both patients and healthcare providers. These conditions often present with atypical symptoms, making diagnosis and treatment a formidable task. In recent years, artificial intelligence and natural language processing technologies have shown great promise in assisting medical professionals in diagnosing and managing such conditions. This paper explores the role of ChatGPT, an advanced artificial intelligence model, in improving the diagnosis and treatment of rare and complex diseases. By analyzing its potential applications, limitations, and ethical considerations, we demonstrate how ChatGPT can contribute to better patient outcomes and enhance the healthcare system's overall effectiveness.

Lifetime risks of second primary malignancies after pediatric Hodgkin lymphoma and non-Hodgkin lymphoma.

OBJECTIVES: Survivors after pediatric Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are with lifetime risk for second primary malignancy (SPM). This necessitates a thorough analysis to better understand the potential long-term health implications for these individuals. METHODS: We used a US-wide population-based cancer registry data to quantify the SPM risk and identify its incidence patterns among pediatric lymphoma patients. RESULTS: We observed 4.74-fold (95% CI 4.27-5.25) and 3.40-fold (95% CI 2.78-4.10) increased risks of SPM in survivors after pediatric HL and NHL, respectively. Through over 40 years' follow-up, the cumulative incidence of SPM for pediatric lymphoma was persistently increasing, and here we firstly report the high 40-year cumulative incidence rates of SPM, 22.2% for HL and 12.6% for NHL, suggesting that SPM accounts for a great proportion of deaths among survivors. Of 6805 pediatric lymphomas, 462 (6.36%) developed a SPM, especially second breast and thyroid cancer, followed by hematologic neoplasms including leukemia and NHL. The competing risk analysis demonstrated gender, lymphoma subtype and radiotherapy were significantly associated with SPM. Different risk patterns of SPM were identified between pediatric HL and NHL. Chemotherapy accelerated SPM development but did not increase its incidence risk. CONCLUSION: Overall, patients after pediatric lymphoma can be with high lifetime risk of SPM, and more attention should be paid to SPM-related signs for early detection and intervention.

Alleviating CB2-Dependent ER Stress and Mitochondrial Dysfunction Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment.

Augmentation of endoplasmic reticulum (ER) stress may trigger excessive oxidative stress, which induces mitochondrial dysfunction. The fatty acid amide hydrolase inhibitor, URB597, shows anti-oxidation characteristics in multiple neurological disorders. The present study aimed to determine whether inhibition of ER stress was involved in the protective effects of URB597 against chronic cerebral hypoperfusion (CCH)-induced cognitive impairment. Hippocampal HT-22 cells were exposed to oxygen-glucose deprivation. The cell viability, apoptosis, ER stress, mitochondrial ATP, and oxidative stress levels were assessed following treatment with URB597, benzenebutyric acid (4-PBA), and thapsigargin (TG). Furthermore, the effects of URB597 on ER stress and related pathways were investigated in the CCH animal model, including Morris water maze testing of cognition, western blotting analysis of ER stress signaling, and transmission electron microscopy of mitochondrial and ER ultrastructure changes. The results suggested that cerebral ischemia caused ER stress with upregulation of ER stress signaling-related proteins, mitochondrial dysfunction, neuronal apoptosis, ultrastructural injuries of mitochondria-associated ER membranes, and cognitive decline. Co-immunoprecipitation experiments confirmed the interaction between CB2 and ß-Arrestin1. Inhibiting ER stress by URB597 improved these changes by activating CB2/ß-Arrestin1 signaling, which was reversed by the CB2 antagonist, AM630. Together, the results identified a novel mechanism of URB597, involving CCH-induced cognitive impairment alleviation of CB2-dependent ER stress and mitochondrial dysfunction. Furthermore, this study identified CB2 as a potential target for therapy of ischemic cerebrovascular diseases.

ZmNRT1.1B (ZmNPF6.6) determines nitrogen use efficiency via regulation of nitrate transport and signalling in maize.

Nitrate (NO3 - ) is crucial for optimal plant growth and development and often limits crop productivity under low availability. In comparison with model plant Arabidopsis, the molecular mechanisms underlying NO3 - acquisition and utilization remain largely unclear in maize. In particular, only a few genes have been exploited to improve nitrogen use efficiency (NUE). Here, we demonstrated that NO3 - -inducible ZmNRT1.1B (ZmNPF6.6) positively regulated NO3 - -dependent growth and NUE in maize. We showed that the tandem duplicated proteoform ZmNRT1.1C is irrelevant to maize seedling growth under NO3 - supply; however, the loss of function of ZmNRT1.1B significantly weakened plant growth under adequate NO3 - supply under both hydroponic and field conditions. The 15 N-labelled NO3 - absorption assay indicated that ZmNRT1.1B mediated the high-affinity NO3 - -transport and root-to-shoot NO3 - translocation. Transcriptome analysis further showed, upon NO3 - supply, ZmNRT1.1B promotes cytoplasmic-to-nuclear shuttling of ZmNLP3.1 (ZmNLP8), which co-regulates the expression of genes involved in NO3 - response, cytokinin biosynthesis and carbon metabolism. Remarkably, overexpression of ZmNRT1.1B in modern maize hybrids improved grain yield under N-limiting fields. Taken together, our study revealed a crucial role of ZmNRT1.1B in high-affinity NO3 - transport and signalling and offers valuable genetic resource for breeding N use efficient high-yield cultivars.