GSTM3 enhances radiosensitivity of nasopharyngeal carcinoma by promoting radiation-induced ferroptosis through USP14/FASN axis and GPX4.

BACKGROUND: Radiotherapy is a critical treatment modality for nasopharyngeal carcinoma (NPC). However, the mechanisms underlying radiation resistance and tumour recurrence in NPC remain incompletely understood. METHODS: Oxidised lipids were assessed through targeted metabolomics. Ferroptosis levels were evaluated using cell viability, clonogenic survival, lipid peroxidation, and transmission electron microscopy. We investigated the biological functions of glutathione S-transferase mu 3 (GSTM3) in cell lines and xenograft tumours. Co-immunoprecipitation, mass spectrometry, and immunofluorescence were conducted to explore the molecular mechanisms involving GSTM3. Immunohistochemistry was performed to investigate the clinical characteristics of GSTM3. RESULTS: Ionising radiation (IR) promoted lipid peroxidation and induced ferroptosis in NPC cells. GSTM3 was upregulated following IR exposure and correlated with IR-induced ferroptosis, enhancing NPC radiosensitivity in vitro and in vivo. Mechanistically, GSTM3 stabilised ubiquitin-specific peptidase 14 (USP14), thereby inhibiting the ubiquitination and subsequent degradation of fatty acid synthase (FASN). Additionally, GSTM3 interacted with glutathione peroxidase 4 (GPX4) and suppressed GPX4 expression. Combining IR treatment with ferroptosis inducers synergistically improved NPC radiosensitivity and suppressed tumour growth. Notably, a decrease in GSTM3 abundance predicted tumour relapse and poor prognosis. CONCLUSIONS: Our findings elucidate the pivotal role of GSTM3 in IR-induced ferroptosis, offering strategies for the treatment of radiation-resistant or recurrent NPC.

Optimized nitrogen application ameliorates the photosynthetic performance and yield potential in peanuts as revealed by OJIP chlorophyll fluorescence kinetics.

BACKGROUND: Nitrogen (N) is a crucial element for increasing photosynthesis and crop yields. The study aims to evaluate the photosynthetic regulation and yield formation mechanisms of different nodulating peanut varieties with N fertilizer application. METHOD: The present work explored the effect of N fertilizer application rates (N0, N45, N105, and N165) on the photosynthetic characteristics, chlorophyll fluorescence characteristics, dry matter, N accumulation, and yield of four peanut varieties. RESULTS: The results showed that N application increased the photosynthetic capacity, dry matter, N accumulation, and yield of peanuts. The measurement of chlorophyll a fluorescence revealed that the K-phase, J-phase, and I-phase from the OJIP curve decreased under N105 treatment compared with N0, and WOI, ET0/CSM, RE0/CSM, ET0/RC, RE0/RC, φPo, φEo, φRo, and Ψ0 increased, whereas VJ, VI, WK, ABS/RC, TR0/RC, DI0/RC, and φDo decreased. Meanwhile, the photosystem activity and electron transfer efficiency of nodulating peanut varieties decreased with an increase in N (N165). However, the photosynthetic capacity and yield of the non-nodulating peanut variety, which highly depended on N fertilizer, increased with an increase in N. CONCLUSION: Optimized N application (N105) increased the activity of the photosystem II (PSII) reaction center, improved the electron and energy transfer performance in the photosynthetic electron transport chain, and reduced the energy dissipation of leaves in nodulating peanut varieties, which is conducive to improving the yield. Nevertheless, high N (N165) had a positive effect on the photosystem and yield of non-nodulating peanut. The results provide highly valuable guidance for optimizing peanut N management and cultivation measures.

The Simpler the Better: Ultrafast Air-Plasma Synthesis of 3D Crosslinked Graphene Nanoscroll-Nanosheet Aerogels at Room Temperature for Capacitive Deionization.

Graphene nanoscroll (GNS) is an important 1D tubular form of graphene-derivative materials, which has garnered widely attention. However, conventional fabrication methods commonly suffer from complex processing and time-consuming. Herein, with graphene oxide (GO) as a precursor, the study puts forward a facile air-plasma synthesis strategy to fabricate 3D graphene nanoscroll-nanosheet aerogels (GSSA). It is demonstrated that without using any chemical additives, a highly efficient reduction-exfoliation-scrolling process can be achieved all-in-one at room temperature within 1 s. The GNSs "grew" from 2D graphene sheets and firmly cross-linked them together, and they not only provide a shortcut path for electron transport but also act as intrinsic spacers to prevent restacking of graphene sheets. When using as an electrode material for capacitive deionization (CDI), GSSA exhibits excellent merits of salt-removal performance. These findings open a new pathway to large-scale synthesis of high-quality and high-purity GNS-based materials with promising applications in CDI and beyond.

Growth of infants delivered by mothers with HIV in Guangxi, China: An 18-month longitudinal follow-up study, 2015-2021.

OBJECTIVES: The prevention of mother-to-child transmission of HIV has been a global success. But little is known about the growth parameters of infants delivered by mothers with HIV or the drug resistance of infants with HIV in China. The study aimed to assess growth parameters and drug resistance in Chinese infants exposed to HIV. METHODS: We conducted an 18-month longitudinal follow-up study of 3283 infants (3222 without HIV; 61 with HIV) born to mothers with HIV in the Guangxi Zhuang Autonomous Region between January 2015 and December 2021. The weight and length of all participants was recorded. In addition, genetic subtypes and drug resistance analysis were performed for infants with HIV. RESULTS: Compared with infants without HIV, those with HIV had significantly lower weight/length Z-scores, except at 18 months of age. The length/age Z-scores of infants with HIV was significantly reduced, except at 1 month of age. The weight/age Z-scores of infants with HIV were significantly lower at all follow-up time points. The weight/length Z-scores of male infants without HIV were significantly lower than for female infants without HIV at all follow-up time points. Male infants without HIV had lower length/age and weight/age Z-scores than female infants at the remaining follow-up points, except at 1 month of age. Of a total of 61 infants with HIV, subtype and drug-resistance data were obtained from 37 (60.66%) samples. Infants with HIV were dominated by the CRF01_AE genotype and showed a diversity of mutation sites dominated by non-nucleoside reverse transcriptase inhibitor resistance. CONCLUSION: Our study demonstrates the growth of infants exposed to HIV in southwest China and provides detailed information on subtype distribution and drug resistance of those with HIV. Nutritional support and drug-resistance surveillance for infants exposed to HIV need to be strengthened.

Construction of a BiOCl/Bi2O2CO3 S-Scheme Heterojunction Photocatalyst via Sharing [Bi2O2]2+ Slabs with Enhanced Photocatalytic H2O2 Production Performance.

The construction of a close contact interface is key to enhancing the photocatalytic activity in heterojunctions. In the work, the BiOCl/Bi2O2CO3 of sharing [Bi2O2]2+ slabs S-scheme heterojunction was prepared by a HCl in situ etching method. The optimal composite photocatalyst could accomplish sizable productivity of H2O2 to 2562.95 µmol g-1 h-1 under simulated solar irradiation, higher than that of primitive Bi2O2CO3 and BiOCl. Moreover, the synthesized catalysts showed good stability. The band structures of BiOCl and Bi2O2CO3 were determined, confirming the formation of BiOCl/Bi2O2CO3 S-scheme heterojunction The BiOCl/Bi2O2CO3, which obviously improved the separation efficiency of photoinduced carriers and effectively enhanced the redox ability of the photocatalyst. In addition, density functional theory (DFT) calculations were utilized to analyze the electron transfer properties and the constitution of the built-in electric field at the interface of BiOCl and Bi2O2CO3. The photocatalytic reaction process was further researched by electron paramagnetic resonance (EPR), indicating the active species in the photocatalytic production of hydrogen peroxide. Eventually, a feasible S-scheme electron transfer mechanism on the BiOCl/Bi2O2CO3 heterojunction during the photocatalytic H2O2 production process was proposed and discussed. This work provides a reliable strategy for the fine design of the S-scheme heterojunction.

A high-performance, sensitive, low-cost LIG/PDMS strain sensor for impact damage monitoring and localization in composite structures.

Health monitoring of composite structures in aircraft is critical, as these structures are commonly utilized in weight-sensitive areas and innovative designs that directly impact flight safety and reliability. Traditional monitoring methods have limitations in monitoring area, strain limit, and signal processing. In this paper, a multifunctional sensor has been developed using acid-treated laser-induced graphene (A-LIG) with a multi-layer three-dimensional conductive network. Compared to untreated laser-induced graphene, the sensitivity of A-LIG sensor is increased by 100%. Furthermore, PDMS is used to fill the pores, which improves the fatigue performance of the A-LIG sensor. To obtain clear monitoring results, a data conversion algorithm is provided to convert the electrical signal obtained by the sensor into a strain field contour cloud map. The impact test of the A-LIG/PDMS sensor on the carbon fiber panel of the aircraft wing box segment verifies the effectiveness of its strain sensing. This work introduces a novel approach to fabricating flexible sensors with improved sensitivity, extended strain range, and cost-effectiveness. The sensor exhibits high sensitivity (gauge factor,GF≈ 387), is low hysteresis (∼53 ms), and has a wide working range (up to 47%), and a highly stable and reproducible response over multiple test cycles (>18 000) with good switching response. It presents a promising and innovative direction for utilizing flexible sensors in the field of aircraft structural health monitoring.

Dauresorcinols A and B, two pairs of merosesquiterpenoid enantiomers with new carbon skeletons from Rhododendron dauricum.

Five pairs of new merosesquiterpenoid enantiomers, named dauresorcinols A-E (1-5), were isolated from the leaves of Rhododendron dauricum. Their structures were elucidated by comprehensive spectroscopic data analysis, quantum chemical calculations, Rh2(OCOCF3)4-induced ECD, and single-crystal X-ray diffraction analysis. Dauresorcinols A (1) and B (2) possess two new merosesquiterpene skeletons bearing an unprecedented 2,6,7,10,14-pentamethyl-11-oxatetracyclo[8.8.0.02,7.012,17]octadecane and a caged 15-isohexyl-1,5,15-trimethyl-2,10-dioxatetracyclo[7.4.1.111,14.03,8]pentadecane motif, respectively. Plausible biosynthetic pathways of 1-5 are proposed involving key oxa-electrocyclization and Wagner-Meerwein rearrangement reactions. (+)/(-)-1 and 3-5 showed potent α-glucosidase inhibitory activity, 3 to 22 times stronger than acarbose, an antidiabetic drug targeting α-glucosidase. Docking results provide a basis to design and develop merosesquiterpenoids as potent α-glycosidase inhibitors.

Discovery of highly functionalized grayanane diterpenoids from the flowers of Rhododendron molle as potent analgesics.

A systematical investigation on the chemical constituents of the flowers of Rhododendron molle (Ericaceae) led to the isolation and characterization of thirty-eight highly functionalized grayanane diterpenoids (1-38), including twelve novel analogues molleblossomins A-L (1-12). Their structures were elucidated by comprehensive methods, including 1D and 2D NMR analysis, calculated ECD, 13C NMR calculations with DP4+ probability analysis, and single crystal X-ray diffraction. Molleblossomins A (1), B (2), and E (5) are the first representatives of 2ß,3ß:9ß,10ß-diepoxygrayanane, 2,3-epoxygrayan-9(11)-ene, and 5,9-epoxygrayan-1(10),2(3)-diene diterpenoids, respectively. Molleblossomins G (7) and H (8) represent the first examples of 1,3-dioxolane-grayanane conjugates furnished with the acetaldehyde and 4-hydroxylbenzylidene acetal moieties, respectively. All grayanane diterpenoids 1-38 were screened for their analgesic activities in the acetic acid-induced writhing model, and all of them exhibited significant analgesic activities. Diterpenoids 6, 13, 14, 17, 20, and 25 showed more potent analgesic effects than morphine at a lower dose of 0.2 mg/kg, with the inhibition rates of 51.4%, 68.2%, 94.1%, 66.9%, 97.7%, and 60.0%, respectively. More importantly, even at the lowest dose of 0.04 mg/kg, rhodomollein X (14), rhodojaponin VI (20), and rhodojaponin VII (22) still significantly reduced the number of writhes in the acetic acid-induced pain model with the percentages of 61.7%, 85.8%, and 64.6%, respectively. The structure-activity relationship was summarized and might provide some hints to design novel analgesics based on the functionalized grayanane diterpenoids.

Microplastics and benthic animals reshape the geochemical characteristics of dissolved organic matter by inducing changes in keystone microbes in riparian sediments.

Dissolved organic matter (DOM) in riparian sediments plays a vital role in regulating element cycling and pollutant behavior of river ecosystems. Microplastics (MPs) and benthic animals (BAs) have been frequently detected in riparian sediments, influencing the substance transformation in river ecosystems. However, there is still a lack of systematic investigation on the effects of MPs and BAs on sediment DOM. This study investigated the impact of MPs and BAs on the geochemical characteristics of DOM in riparian sediments and their microbial mechanisms. The results showed that MPs and BAs increased sediment DOC concentration by 34.24%∼232.97% and promoted the conversion of macromolecular components to small molecular components, thereby reducing the humification degree of DOM. Mathematical model verified that the changes of keystone microbes composition in sediments were direct factors affecting the characteristics of DOM in riparian sediment. Especially, MPs tolerant microbes, including Planctomicrobium, Rhodobacter, Hirschia and Lautropia, significantly increased DOC concentration and decreased humification degree (P < 0.05). In addition, MPs and BAs could also influence keystone microbes in sediments by altering the structure of microbial network, thereby indirectly affecting DOM characteristics. The study demonstrates the pollution behavior of MPs in river ecosystems and provides a basis for protecting the ecological function of riparian sediments from MPs pollution.

Improving the substrate binding of acetyl-CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering.

Malonyl-CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid-derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme-engineering approach to improve the binding of acetyl-CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl-CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding-free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be -52.66 ± 0.11 kcal/mol for the wild type, -55.87 ± 0.16 kcal/mol for the S343A mutant, -60.52 ± 0.25 kcal/mol for T347W mutant, and -59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.

A chronic stress-induced microbiome perturbation, highly enriched in Ruminococcaceae_UCG-014, promotes colorectal cancer growth and metastasis.

Purpose: Mounting evidence indicates that psychological stress adversely affects cancer progression including tumor growth and metastasis. The aim of this study was to investigate the role of chronic stress-induced microbiome perturbation in colorectal cancer (CRC) progression. Methods: Chronic restraint stress (CRS) was used to establish the chronic stress mouse model, behavioral tests were used for the CRS model evaluation. Subcutaneous xenograft model and lung metastasis model were established to investigate the growth and metastasis of CRC promoted by CRS exposure. 16S rRNA gene sequencing and liquid chromatograph-mass spectrometer (LC-MS) were applied to observe the effects of CRS exposure on the alteration of the gut microbiome and microbial metabolites. Bioinformatics analysis and correlation analyses were applied to analyse the changes in the frequency of body mass, tumor volume, inflammatory factors, neuroendocrine hormones and metabolites of the gut microbiota. Results: In this study, we identifed that CRS exposure model was appropriately constructed by achieving expected increases in disease activity index and enhanced depressive-like behaviors. CRS exposure can promote growth and metastasis of CRC. Besides, the data indicated that CRS exposure not only increased the neuro- and immune-inflammation, but also weakened the gut mucosal immunological function. The 16s rRNA gene sequencing data showed that CRS exposure increased the abundance of g_Ruminococcaceae_UCG_014. Furthermore, the LC-MS data indicated that with only 2 exceptions of carpaine and DG (15:0/20:4(5Z,8Z,11Z,14Z)/0:0), the majority of these 24 metabolites were less abundant in CRS-exposed mice. Bioinformatics analysis and correlation analyses indicated that only Ruminoscoccaceae-UCG-014 was significantly associated with inflammation (IL-6), neurotransmission (5-HT), and microbial metabolism (PS). Conclusion: CRS exposure altered diversity, composition and metabolites of the gut microbiome, with Ruminococcaceae_UCG-014 perturbation consistently correlated to inflammatory responses, suggesting a particular role of this bacterial genus in CRC growth and metastasis.

Contextual Acceptance of COVID-19 Mitigation Mobile Apps in the United States: Mixed Methods Survey Study on Postpandemic Data Privacy.

BACKGROUND: The COVID-19 pandemic gave rise to countless user-facing mobile apps to help fight the pandemic ("COVID-19 mitigation apps"). These apps have been at the center of data privacy discussions because they collect, use, and even retain sensitive personal data from their users (eg, medical records and location data). The US government ended its COVID-19 emergency declaration in May 2023, marking a unique time to comprehensively investigate how data privacy impacted people's acceptance of various COVID-19 mitigation apps deployed throughout the pandemic. OBJECTIVE: This research aims to provide insights into health data privacy regarding COVID-19 mitigation apps and policy recommendations for future deployment of public health mobile apps through the lens of data privacy. This research explores people's contextual acceptance of different types of COVID-19 mitigation apps by applying the privacy framework of contextual integrity. Specifically, this research seeks to identify the factors that impact people's acceptance of data sharing and data retention practices in various social contexts. METHODS: A mixed methods web-based survey study was conducted by recruiting a simple US representative sample (N=674) on Prolific in February 2023. The survey includes a total of 60 vignette scenarios representing realistic social contexts that COVID-19 mitigation apps could be used. Each survey respondent answered questions about their acceptance of 10 randomly selected scenarios. Three contextual integrity parameters (attribute, recipient, and transmission principle) and respondents' basic demographics are controlled as independent variables. Regression analysis was performed to determine the factors impacting people's acceptance of initial data sharing and data retention practices via these apps. Qualitative data from the survey were analyzed to support the statistical results. RESULTS: Many contextual integrity parameter values, pairwise combinations of contextual integrity parameter values, and some demographic features of respondents have a significant impact on their acceptance of using COVID-19 mitigation apps in various social contexts. Respondents' acceptance of data retention practices diverged from their acceptance of initial data sharing practices in some scenarios. CONCLUSIONS: This study showed that people's acceptance of using various COVID-19 mitigation apps depends on specific social contexts, including the type of data (attribute), the recipients of the data (recipient), and the purpose of data use (transmission principle). Such acceptance may differ between the initial data sharing and data retention practices, even in the same context. Study findings generated rich implications for future pandemic mitigation apps and the broader public health mobile apps regarding data privacy and deployment considerations.

Divergent Synthetic Approach to Grayanane Diterpenoids.

The total syntheses of nine grayanane diterpenoids, namely, GTX-II (1), GTX-III (2), rhodojaponin III (3), GTX-XV (4), principinol D (5), iso-GTX-II (6), 1,5-seco-GTX-Δ1,10-ene (7), and leucothols B (8) and D (9), that belong to five distinct subtypes, were disclosed in a divergent manner. Among them, six members were accomplished for the first time. The concise synthetic approach features three key transformations: (1) an oxidative dearomatization-induced [5 + 2] cycloaddition/pinacol rearrangement cascade to assemble the bicyclo[3.2.1]octane carbon framework (CD rings); (2) a photosantonin rearrangement to build up the 5/7 bicycle (AB rings) of 1-epi-grayanoids; and (3) a Grob fragmentation/carbonyl-ene process to access four additional subtypes of grayanane skeletons. Density functional theory calculations were performed to elucidate the mechanistic origins of the crucial divergent transformation, which combined with late-stage synthetic findings provided insights into the biosynthetic relationships between these diverse skeletons.

Piericones A and B as Potent Antithrombotics: Nanomolar Noncompetitive Protein Disulfide Isomerase Inhibitors with an Unexpected Chemical Architecture.

Extracellular protein disulfide isomerase (PDI) is a promising target for thrombotic-related diseases. Four potent PDI inhibitors with unprecedented chemical architectures, piericones A-D (1-4), were isolated from Pieris japonica. Their structures were elucidated by spectroscopic data analysis, chemical methods, quantum 13C nuclear magnetic resonance DP4+ and electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Piericones A (1) and B (2) were nanomolar noncompetitive PDI inhibitors possessing an unprecedented 3,6,10,15-tetraoxatetracyclo[7.6.0.04,9.01,12]pentadecane motif with nine contiguous stereogenic centers. Their biosynthetic pathways were proposed to include a key intermolecular aldol reaction and an intramolecular 1,2-migration reaction. Piericone A (1) significantly inhibited in vitro platelet aggregation and fibrin formation and in vivo thrombus formation via the inhibition of extracellular PDI without increasing the bleeding risk. The molecular docking and dynamics simulation of 1 and 2 provided a novel structure basis to develop PDI inhibitors as potent antithrombotics.

Recruitment of phosphatase PP2A by RACK1 adaptor protein deactivates transcription factor IRF3 and limits type I interferon signaling.

The transcription factor IRF3 is a central regulator of type I interferon (IFN) signaling. The mechanisms underlying deactivation of IRF3 are poorly understood although many studies suggest that IRF3 activity is terminated through degradation after viral infection. Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3 pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection. After challenge with LPS, poly(I:C), or low-titer SeV, activated IRF3 was dephosphorylated and returned to resting state without being degraded, although high-titer SeV infection triggered the degradation of IRF3. Furthermore, PP2A-deficient macrophages showed enhanced type I IFN signaling upon LPS, poly(I:C), and SeV challenge and protected mice from lethal vesicular stomatitis virus infection. Therefore, dephosphorylation of IRF3 is a deactivation mechanism that contributes to termination of IRF3-type I IFN signaling.

An ecdysteroid-regulated 16-kDa protein homolog participates in the immune response of the crayfish Procambarus clarkii.

An ecdysteroid-regulated 16-kDa protein homolog (named Pc-E16), encoding 150 amino acid residues with a conserved MD-2-related lipid-recognition domain, was first identified in Procambarus clarkii. Phylogenetic analyses indicated similarity between Pc-E16 and 16-kDa proteins from Aplysia californica and insects. Recombinant Pc-E16 protein was successfully expressed in BL21 (DE3) Escherichia coli cells, and polyclonal antibodies against purified Pc-E16 proteins were prepared. In comparison with other tissues, Pc-E16 was highly expressed in the intestine; real-time PCR and Western blotting results indicated that Pc-E16 expression was significantly induced by lipopolysaccharides in hepatopancreas and hemocytes. Pc-E16-mediated signaling pathways were investigated by digital gene expression analysis following RNA interference targeting Pc-E16. A total of 6103 differentially expressed genes (DEGs) were identified, of which 3318 were up- and 2785 were downregulated. Many DEGs were involved in binding and catalytic activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that DEGs were clustered into 225 pathways, and 15 significantly enriched pathways were identified at the immune system level. In addition, the expression level of Pc-E16 in hemocytes and hepatopancreas was obviously downregulated at 48 h after dsRNA injection, and Pc-E16-RNAi treatment affected the expression levels of immune-related genes. Altogether, our results suggest that Pc-E16 is involved in the innate immune response of P. clarkii.

Highly oxygenated grayanane diterpenoids with structural diversity from the flowers of Rhododendron dauricum and their analgesic activities.

Twenty-eight grayanane diterpenoids (1-28) including 13 new ones, named daublossomins A-M (1-13), and two new natural products, 3-O-acetylgrayanotoxin II (14) and 10-epi-grayanotoxin III (15), were isolated from the flowers of Rhododendron dauricum L. (Ericaceae). Their structures were elucidated by means of comprehensive spectroscopic methods and quantum chemical calculations (13C NMR-DP4+ analysis and calculated ECD), and the absolute configurations of ten grayanane diterpenoids 1, 4, 5, 7, 8, 22, 23, 25, 27, and 28 were determined by X-ray crystallographic analysis. Daublossomin A (1) represents the first example of an 11,16-epoxygrayan-6-one diterpenoid. Daublossomins B (2) and C (3) are the first examples of 9ß,10ß-epoxygrayanane diterpenoids, and daublossomin I (9) is the second conjugated grayan-1(5),6(7),9(10)-triene diterpenoid. Compounds 1-11 and 13-27 were evaluated for their analgesic activities in the HOAc-induced writhing test in mice, and 1-8, 10, 11, 13, 15, 17, 18, 22-24, and 26 exhibited significant analgesic effects at a dose of 5.0 mg/kg (inhibition rates > 50%). Among them, daublossomins A (1) and F (6) still showed potent analgesic activity even at a lower dose of 0.2 mg/kg with the inhibition rates of 54.4% and 55.2%, respectively. Grayanotoxin III (20) showed more potent analgesic activities than the positive control, morphine, at a dose of 0.04 mg/kg. A preliminary structure-activity relationship for the analgesic grayanane diterpenoids was discussed, providing some useful clues to design and develop structurally novel potent analgesics.

Sustainable preparation of high-calorific value and low-N and S energy products through the low-temperature alkali fusion of coal gasification fine ash.

Coal gasification fine ash (CGFA) is characterized by high yield, high carbon content, and difficult recovery. This results in waste of coal resources and serious environmental pollution. To address this issue, a novel green deashing process is proposed in this study to modify CGFA into deashed carbon (DAC) with a high calorific value and an ash content of less than 5% through a low-temperature alkaline fusion process. Compared with traditional alkaline fusion (which is carried out at 600-1000 °C), low-temperature alkaline fusion treatment can efficiently remove ash minerals in the temperature range of 300-450 °C, which is beneficial to the efficient recovery of residual carbon in DA, while simultaneously improving the physicochemical properties and energy characteristics of DAC, thereby improving its combustion performance. At an alkali fusion temperature of 350 °C, a NaOH:DA ratio of 4.5:1, and a reaction time of 40 min, the resulting DAC product had ash content of 2.28%, combustible material recovery (CMR) of 82.03%, higher heating value (HHV) of 31.07 MJ kg-1, and SBET of 445.43 m2 g-1. In comparison, it was found that low-temperature alkali fusion significantly improved the deashing of CGFA when compared to existing deashing technologies. These results strongly suggest that this innovative deashing method can modify CGFA into a high-calorific value and low-N and S fuel, thereby providing a cost-effective and sustainable utilization method for CGFA.

Impact of automatic acquisition of key clinical information on the accuracy of electrocardiogram interpretation: a cross-sectional study.

BACKGROUND: The accuracy of electrocardiogram (ECG) interpretation by doctors are affected by the available clinical information. However, having a complete set of clinical details before making a diagnosis is very difficult in the clinical setting especially in the early stages of the admission process. Therefore, we developed an artificial intelligence-assisted ECG diagnostic system (AI-ECG) using natural language processing to provide screened key clinical information during ECG interpretation. METHODS: Doctors with varying levels of training were asked to make diagnoses from 50 ECGs using a common ECG diagnosis system that does not contain clinical information. After a two-week-blanking period, the same set of ECGs was reinterpreted by the same doctors with AI-ECG containing clinical information. Two cardiologists independently provided diagnostic criteria for 50 ECGs, and discrepancies were resolved by consensus or, if necessary, by a third cardiologist. The accuracy of ECG interpretation was assessed, with each response scored as correct/partially correct = 1 or incorrect = 0. RESULTS: The mean accuracy of ECG interpretation was 30.2% and 36.2% with the common ECG system and AI-ECG system, respectively. Compared to the unaided ECG system, the accuracy of interpretation was significantly improved with the AI-ECG system (P for paired t-test = 0.002). For senior doctors, no improvement was found in ECG interpretation accuracy, while an AI-ECG system was associated with 27% higher mean scores (24.3 ± 9.4% vs. 30.9 ± 10.6%, P = 0.005) for junior doctors. CONCLUSION: Intelligently screened key clinical information could improve the accuracy of ECG interpretation by doctors, especially for junior doctors.

A Comprehensive Evolutionary Study of Chloroplast RNA Editing in Gymnosperms: A Novel Type of G-to-A RNA Editing Is Common in Gymnosperms.

Although more than 9100 plant plastomes have been sequenced, RNA editing sites of the whole plastome have been experimentally verified in only approximately 21 species, which seriously hampers the comprehensive evolutionary study of chloroplast RNA editing. We investigated the evolutionary pattern of chloroplast RNA editing sites in 19 species from all 13 families of gymnosperms based on a combination of genomic and transcriptomic data. We found that the chloroplast C-to-U RNA editing sites of gymnosperms shared many common characteristics with those of other land plants, but also exhibited many unique characteristics. In contrast to that noted in angiosperms, the density of RNA editing sites in ndh genes was not the highest in the sampled gymnosperms, and both loss and gain events at editing sites occurred frequently during the evolution of gymnosperms. In addition, GC content and plastomic size were positively correlated with the number of chloroplast RNA editing sites in gymnosperms, suggesting that the increase in GC content could provide more materials for RNA editing and facilitate the evolution of RNA editing in land plants or vice versa. Interestingly, novel G-to-A RNA editing events were commonly found in all sampled gymnosperm species, and G-to-A RNA editing exhibits many different characteristics from C-to-U RNA editing in gymnosperms. This study revealed a comprehensive evolutionary scenario for chloroplast RNA editing sites in gymnosperms, and reported that a novel type of G-to-A RNA editing is prevalent in gymnosperms.