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Ammonia (NH 3 ) is pivotal to the fertilizer industry and one of the most commonly produced chemicals 1 . The direct use of atmospheric nitrogen (N 2 ) had been challenging, owing to its large bond energy (945 kilojoules per mole) 2 , 3 , until the development of the Haber–Bosch process. Subsequently, many strategies have been explored to reduce the activation barrier of the N≡N bond and make the process more efficient. These include using alkali and alkaline earth metal oxides as promoters to boost the performance of traditional iron- and ruthenium-based catalysts 4 – 6 via electron transfer from the promoters to the antibonding bonds of N 2 through transition metals 7 , 8 . An electride support further lowers the activation barrier because its low work function and high electron density enhance electron transfer to transition metals 9 , 10 . This strategy has facilitated ammonia synthesis from N 2 dissociation 11 and enabled catalytic operation under mild conditions; however, it requires the use of ruthenium, which is expensive. Alternatively, it has been shown that nitrides containing surface nitrogen vacancies can activate N 2 (refs. 12 – 15 ). Here we report that nickel-loaded lanthanum nitride (LaN) enables stable and highly efficient ammonia synthesis, owing to a dual-site mechanism that avoids commonly encountered scaling relations. Kinetic and isotope-labelling experiments, as well as density functional theory calculations, confirm that nitrogen vacancies are generated on LaN with low formation energy, and efficiently bind and activate N 2 . In addition, the nickel metal loaded onto the nitride dissociates H 2 . The use of distinct sites for activating the two reactants, and the synergy between them, results in the nickel-loaded LaN catalyst exhibiting an activity that far exceeds that of more conventional cobalt- and nickel-based catalysts, and that is comparable to that of ruthenium-based catalysts. Our results illustrate the potential of using vacancy sites in reaction cycles, and introduce a design concept for catalysts for ammonia synthesis, using naturally abundant elements. Ammonia is synthesized using a dual-site approach, whereby nitrogen vacancies on LaN activate N 2 , which then reacts with hydrogen atoms produced over the Ni metal to give ammonia.

NRC publication: Yes

The tunability of reaction pathways is required for exploring efficient and low cost catalysts for ammonia synthesis. There is an obstacle by the limitations arising from scaling relation for this purpose. Here, we demonstrate that the alkali earth imides ( Ae NH) combined with transition metal (TM = Fe, Co and Ni) catalysts can overcome this difficulty by utilizing functionalities arising from concerted role of active defects on the support surface and loaded transition metals. These catalysts enable ammonia production through multiple reaction pathways. The reaction rate of Co/SrNH is as high as 1686.7 mmol·g Co −1 ·h −1 and the TOFs reaches above 500 h −1 at 400 °C and 0.9 MPa, outperforming other reported Co-based catalysts as well as the benchmark Cs-Ru/MgO catalyst and industrial wüstite-based Fe catalyst under the same reaction conditions. Experimental and theoretical results show that the synergistic effect of nitrogen affinity of 3d TMs and in-situ formed NH 2− vacancy of alkali earth imides regulate the reaction pathways of the ammonia production, resulting in distinct catalytic performance different from 3d TMs. It was thus demonstrated that the appropriate combination of metal and support is essential for controlling the reaction pathway and realizing highly active and low cost catalysts for ammonia synthesis. The presence of electrically active defects on the surface of the support has been shown to be effective for N 2 activation. Here the authors discover that electron-rich polyanionic NH 2− defect allows for efficient ammonia synthesis via multiple reaction pathway by incorporating various affordable transition metals.

Increased endoplasmic reticulum (ER) stress is one of the central mechanisms that lead to dysregulated metabolic homeostasis in obesity. It is thus crucial to understand the underpinnings of the mechanisms that lead to the development of ER stress. A high level of ER Ca²⁺ is imperative for maintenance of normal ER function and this high Ca²⁺ concentration of ER is maintained by sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA). Here, we show that SERCA2b protein and mRNA levels are dramatically reduced in the liver of obese mice and restoration of SERCA2b in the liver of obese and diabetic mice alleviates ER stress, increases glucose tolerance, and significantly reduces the blood glucose levels. Furthermore, overexpression of SERCA2b in the liver of obese mice significantly reduces the lipogenic gene expression and the triglyceride content in the liver. Our results document the importance of SERCA2b in dysregulated glucose and lipid homeostasis in the liver of obese mice and suggest development of drugs to increase SERCA2b activity for treatment of type 2 diabetes and nonalcoholic steatohepatitis.

During the COVID-19 endemic phase, pulmonary sequelae substantially contributed to disease burden. Immunologic responses may be critical in both acute COVID-19 and in long-term sequelae. We aimed to evaluate associations between convalescent neutralizing antibodies and long-term pulmonary sequelae in patients hospitalized with mild to moderate COVID-19. Among patients who recovered from hospitalization due to COVID-19, those who consented to participate in the study provided convalescent serum between June 2021 and April 2022. These baseline patients were invited for a second follow-up visit between September and November 2023. A serum sample was collected at the second visit, and low-dose chest computed tomography (CT) was performed. Pulmonary sequelae were defined as findings of fibrotic, fibrotic-like, and ground-glass opacities (GGOs). Antibody and cytokine levels were assessed in serum samples from the baseline convalescent phase, and antibody levels were also measured in the serum sample at the second visit. A total of 107 patients were enrolled at baseline, and 37 consented to the second follow-up visit. Most second-visit patients (97.3%, 36/37) did not require an oxygen supply beyond that provided via masks or nasal prongs. Twenty-two patients (59.5%) exhibited pulmonary sequelae on chest CT at a median follow-up period of 27 months (interquartile range 25-28, range 22-30) after hospitalization for COVID-19. Fifteen patients (40.5%) had fibrotic or fibrotic-like pulmonary changes, and twelve (32.4%) had GGOs. Pulmonary sequelae were associated with older age (adjusted odds ratio 1.130, 95% confidence interval 1.028-1.243; P = 0.011). There were no significant differences in convalescent cytokines or neutralizing antibodies between patients with pulmonary sequelae and those without. Pulmonary sequelae were quite common on chest CT after two years of mild to moderate COVID-19 and were associated with older age. The immunological or inflammatory status in the immediate post-acute infection period did not predict long-term complications.

Cerebral small vessel disease (CSVD) is a group of pathologies that affect the cerebral blood vessels. CSVD accounts for 25% of strokes and contributes to 45% of dementia. However, the pathogenesis of CSVD remains unclear, involving a variety of complex mechanisms. CSVD may result from dysfunction in the glymphatic system (GS). The GS contains aquaporin-4 (AQP-4), which is in the perivascular space, at the endfeet of the astrocyte. The GS contributes to the removal of waste products from the central nervous system, occupying perivascular spaces and regulating the exchange and movement of cerebrospinal fluid and interstitial fluid. The GS involves astrocytes and aquaporin channels, which are components of the blood–brain barrier, and problems with them may constitute the pathogenesis of CSVD. Vascular risk factors, including diabetes, dilate the perivascular space, disrupting the glymphatic system and the active regulation of AQP-4. CSVD exacerbation due to disorders of the GS is associated with multiple vasculopathies. Dysfunction of the glymphatic system and AQP-4 interferes with the functioning of the blood–brain barrier, which exacerbates CSVD. In a long-term follow-up of CSVD patients with microbleeds, lacunar infarcts, and white matter hyperintensity, several vascular risk factors, including hypertension, increased the risk of ischemic stroke. Dysfunction of the GS may be the cause of CSVD; however, the underlying treatment needs to be studied further.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea. SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed. SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS.

This study focuses on predicting the prognosis of acute ischemic stroke patients with focal neurologic symptoms using a combination of diffusion-weighted magnetic resonance imaging (DWI) and clinical information. The primary outcome is a poor functional outcome defined by a modified Rankin Scale (mRS) score of 3–6 after 3 months of stroke. Employing nnUnet for DWI lesion segmentation, the study utilizes both multi-task and multi-modality methodologies, integrating DWI and clinical data for prognosis prediction. Integrating the two modalities was shown to improve performance by 0.04 compared to using DWI only. The model achieves notable performance metrics, with a dice score of 0.7375 for lesion segmentation and an area under the curve of 0.8080 for mRS prediction. These results surpass existing scoring systems, showing a 0.16 improvement over the Totaled Health Risks in Vascular Events score. The study further employs grad-class activation maps to identify critical brain regions influencing mRS scores. Analysis of the feature map reveals the efficacy of the multi-tasking nnUnet in predicting poor outcomes, providing insights into the interplay between DWI and clinical data. In conclusion, the integrated approach demonstrates significant advancements in prognosis prediction for cerebral infarction patients, offering a superior alternative to current scoring systems.

Background Non-small cell lung cancer (NSCLC) is associated with abnormal activation of the epidermal growth factor receptor (EGFR) due to overexpression or mutations. While EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib, are used to treat NSCLC, resistance often develops, due to additional EGFR mutations or activation of alternative signaling pathways. Therefore, novel drugs to overcome EGFR-TKI resistance are needed for effective treatment of NSCLC. Narciclasin (Ncs) is a cytotoxic alkaloid from Narcissus species and exhibit antitumor and anti-inflammatory activities. Methods Cell viability assay was assessed using trypan blue staining and the Live/Dead viability assay. The growth inhibitory effects of Ncs were evaluated by WST-1 assay and cell cycle analysis across multiple NSCLC cell lines, including expressing A549 and H1299 (wt-EGFR), gefitinib-resistant H1975 (L858R/T790M-EGFR), gefitinib-sensitive PC-9 (exon 19 deleted-EGFR), and gefitinib-resistant PC-9 derivative, PC-9-GR. Ncs binding to wt-EGFR and mutant EGFRs was simulated with molecular docking models. Ncs effects on EGFR kinase activity was evaluated in vitro kinase assay using wt-EGFR and L858R/T790M-EGFR. Anti-tumor effects of Ncs in vivo were assessed using C. elegans tumor model expressing L858R/T790M-EGFR and mouse model xenografted with A549 and H1975. Histological analysis was conducted to measure EGFR, p-EGFR, and p-STAT3 levels in tumor tissues. Results Ncs exhibited significant growth inhibitory effects on various NSCLC cell lines, including, A549, H1299 and PC-9 cells (gefitinib-sensitive), and H1975 and PC-9-GR cells (gefitinib-resistant). Notably, Ncs dramatically reduced cell growth with IC50 of 22 nM in H1975 cells expressing gefitinib -resistant EGFR mutant, much lower than any other cell lines. Ncs dramatically induced G2/M arrest in H1975 cells. Ncs binds to both wt-EGFR and mutant EGFRs in molecular docking models and preferentially inhibited the kinase activity of L858R/T790M-EGFR compared to wt-EGFR. In a C. elegans tumor model, Ncs reduced the tumor-mimicking multivulva phenotype. Ncs treatment resulted in decreased tumor growth in mice xenografted with A549 and H1975 cells and lowered levels of EGFR, p-EGFR, and p-STAT3 in tumor tissues. Conclusions Our results suggest that Ncs exerts anti-tumor activity by inhibiting EGFR activity and downstream signaling. This effect is particularly evident in cases with EGFR mutations that confer resistance to TKIs, including gefitinib, supporting the potential of Ncs as a therapeutic agent for TKI-resistant NSCLC.

Long noncoding RNA growth arrest-specific transcript 5 (GAS5) has been identified as a tumor suppressor due to its downregulation in several cancers. However, our comprehensive analyses revealed aberrant overexpression of GAS5 in various cancers, with a direct association with SMARCA4 in hepatocellular carcinoma (HCC). Differential expression analyses were conducted using publicly available transcriptome datasets. Functional studies of GAS5 and its downstream targets in HCC were performed via small interfering RNA-mediated knockdown in various HCC cell lines, in vivo xenograft mouse models and spontaneous liver cancer models in Ras -transgenic mice. Here we discover that METTL3-mediated N 6 -methyladenosine modification promoted IGF2BP2 binding, stabilizing GAS5 in HCC. GAS5 expression was significantly upregulated in large cohort of patients with solid cancer, including HCC. Targeted disruption of GAS5 resulted in notable inhibition of growth and proliferation in HCC cells. Further analyses demonstrated that GAS5 enhanced in vitro tumorigenesis and metastatic potential of HCC cells. MicroRNA target prediction and functional validation indicated that GAS5 shared a miR-423-3p binding element with SMARCA4 messenger RNA, functioning as a competing endogenous RNA. This interaction was validated in vitro tumorigenesis assays and in vivo models. Moreover, a synergistic effect was observed with vehicle containing a small interfering RNA mixture targeting both GAS5 and SMARCA4 in these animal models. N 6 -methyladenosine-mediated IGF2BP2 binding stabilizes GAS5, which functions as a competing endogenous RNA for miR-423-3p, thereby enhancing the translation of SMARCA4 messenger RNA. GAS5 acts as a crucial regulator of the oncogenic SMARCA4 in hepatocellular carcinogenesis, presenting a potential therapeutic target for the treatment of liver malignancies. Aberrant GAS5 expression drives liver cancer progression Hepatocellular carcinoma (HCC) is a common and deadly liver cancer. Despite research, survival rates have not improved much. Scientists are exploring new ways to treat HCC by targeting RNA changes in cancer cells. This study focuses on a molecule GAS5, which is typically low in many cancers but found at elevated levels in HCC. Researchers found that GAS5 helps cancer grow by interacting with other molecules such as miR-423-3p and SMARCA4. They used lab experiments and mouse models to show that reducing GAS5 or SMARCA4 can slow down cancer growth. They also discovered that GAS5 is stabilized by a chemical change called N 6 -methyladenosine methylation, which helps it function in cancer cells. By targeting these interactions, the researchers suggest new treatment strategies for HCC. In the future, therapies could focus on disrupting these molecular interactions to improve outcomes for patients with liver cancer. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.