Inhibition of DEF-p65 Interactions as a Potential Avenue to Suppress Tumor Growth in Pancreatic Cancer.

The limited success of current targeted therapies for pancreatic cancer underscores an urgent demand for novel treatment modalities. The challenge in mitigating this malignancy can be attributed to the digestive organ expansion factor (DEF), a pivotal yet underexplored factor in pancreatic tumorigenesis. The study uses a blend of in vitro and in vivo approaches, complemented by the theoretical analyses, to propose DEF as a promising anti-tumor target. Analysis of clinical samples reveals that high expression of DEF is correlated with diminished survival in pancreatic cancer patients. Crucially, the depletion of DEF significantly impedes tumor growth. The study further discovers that DEF binds to p65, shielding it from degradation mediated by the ubiquitin-proteasome pathway in cancer cells. Based on these findings and computational approaches, the study formulates a DEF-mimicking peptide, peptide-031, designed to disrupt the DEF-p65 interaction. The effectiveness of peptide-031 in inhibiting tumor proliferation has been demonstrated both in vitro and in vivo. This study unveils the oncogenic role of DEF while highlighting its prognostic value and therapeutic potential in pancreatic cancer. In addition, peptide-031 is a promising therapeutic agent with potent anti-tumor effects.

Global trends and hotspots in research on acupuncture for neurodegenerative diseases over the last decade: a bibliometric and visualization analysis.

Objectives: This study aimed to explore the current status and trends of acupuncture for neurodegenerative diseases (NDs) in the last decade and provide new insights for researchers in future studies. Methods: The publications concerning acupuncture treatment for NDs published between 2014 and 2023 were extracted from the Web of Science Core Collection. We used CiteSpace and VOSviewer to analyze data on numbers of annual publications, countries, institutions, cited journals, cited authors, cited references, keywords, and citation bursts about acupuncture for NDs. Results: A total of 635 publications were obtained from 2014 to 2023. We identified the most prolific journals, countries, institutions, authors, patterns of authorship, and the main direction of future research in the field of acupuncture for NDs in the last decade. The country, institution, and journal with the most publications are China (389 articles), Beijing University of Chinese Medicine (56 articles), and Evidence Based Complementary and Alternative Medicine (42 articles), respectively. The high-frequency keywords focused on "Alzheimer's disease," "Parkinson's disease," "acupuncture," "dementia," and "electroacupuncture." The top five keywords in terms of centrality were "cerebral ischemia," "acupuncture stimulation," "fMRI," "apoptosis," and "deep brain stimulation." Conclusion: The results from this bibliometric study provide insight into the research trends in acupuncture therapy for NDs, and the current status and trends of the past decade, which may help researchers confirm the current status, hotspots, and frontier trends in this field.

Black soldier fly larvae bioconversion and subsequent composting promote larval frass quality during pig and chicken manure transformation process.

This research systematically assessed the changes in carbon, nitrogen and microbial profiling during pig and chicken manure transformation by black soldier fly larvae (BSFL) and subsequent composting process. BSFL had higher conversion efficiency for chicken manure. The pH, phosphorus and potassium contents in fresh BSFL frass increased than raw manure, but conductivity, total-/nitrate-/ammonium-nitrogen decreased. After BSFL conversion, pig manure had a larger nitrogen loss (25 %) while chicken manure had a larger carbon loss (32 %). During subsequent composting, the indicator changes (e.g. humus, ammonium nitrogen) in frass composts basically remained stable after 20-30 days. Compared to natural composts, frass composts had higher humification degree, cellulase activities, and more cellulose-degrading bacteria. Subsequent composting further reduced potential pathogens (reduced by 98.9 %-99.7 % than raw manure), and elevated the aromaticity and humification of frass. The findings gave an insight into the maturation management of manure-sourced insect frass.

Preoperative Molecular Subtype Classification Prediction of Ovarian Cancer Based on Multi-Parametric Magnetic Resonance Imaging Multi-Sequence Feature Fusion Network.

In the study of the deep learning classification of medical images, deep learning models are applied to analyze images, aiming to achieve the goals of assisting diagnosis and preoperative assessment. Currently, most research classifies and predicts normal and cancer cells by inputting single-parameter images into trained models. However, for ovarian cancer (OC), identifying its different subtypes is crucial for predicting disease prognosis. In particular, the need to distinguish high-grade serous carcinoma from clear cell carcinoma preoperatively through non-invasive means has not been fully addressed. This study proposes a deep learning (DL) method based on the fusion of multi-parametric magnetic resonance imaging (mpMRI) data, aimed at improving the accuracy of preoperative ovarian cancer subtype classification. By constructing a new deep learning network architecture that integrates various sequence features, this architecture achieves the high-precision prediction of the typing of high-grade serous carcinoma and clear cell carcinoma, achieving an AUC of 91.62% and an AP of 95.13% in the classification of ovarian cancer subtypes.

Chalcogen Atoms Regulate the Organic Solar Cell Performance of B-N-Based Polymer Donors.

Donor polymers play a key role in the development of organic solar cells (OSCs). B-N-based polymer donors, as new types of materials, have attracted a lot of attention due to their special characteristics, such as high E(T1), small ΔEST, and easy synthesis, and they can be processed with real green solvents. However, the relationship between the chemical structure and device performance has not been systematically studied. Herein, chalcogen atoms that regulate the OSCs performance of B-N-based polymer donors were systematically studied. Fortunately, the substitution of a halogen atom did not affect the high E(T1) and small ΔEST character of the B-N-based polymer. The absorption and energy levels of the polymer were systematically regulated by O, S, and Se atom substitution. The PBNT-TAZ:Y6-BO-based OSCs device demonstrated a high power conversion efficiency of 15.36%. Moreover, the layer-by-layer method was applied to further optimize the device performance, and the PBNT-TAZ/Y6-BO-based OSCs device yielded a PCE of 16.34%. Consequently, we have systematically demonstrated how chalcogen atoms modulated the electronic properties of B-N-based polymers. Detailed and systematic structure-performance relationships are important for the development of next-generation B-N-based materials.

Deciphering and predicting changes in antibiotic resistance genes during pig manure aerobic composting via machine learning model.

Livestock manure is one of the most important pools of antibiotic resistance genes (ARGs) in the environment. Aerobic composting can effectively reduce the spread of antibiotic resistance risk in livestock manure. Understanding the effect of aerobic composting process parameters on manure-sourced ARGs is important to control their spreading risk. In this study, the effects of process parameters on ARGs during aerobic composting of pig manure were explored through data mining based on 191 valid data collected from literature. Machine learning (ML) models (XGBoost and Random Forest) were utilized to predict the rate of ARGs changes during pig manure composting. The model evaluation index of the XGBoost model (R2 = 0.651) was higher than that of the Random Forest (R2 = 0.490), indicating that XGBoost had better prediction performance. Feature importance was further calculated for the XGBoost model, and the XGBoost black box model was interpreted by Shapley additive explanations analysis. Results indicated that the influencing factors on the ARGs variation in pig manure were sequentially divided into thermophilic period, total composting period, composting real time, and thermophilic stage average temperature. The findings gave an insight into the application of ML models to predict and decipher the ARG changes during manure composting and provided suggestions for better composting manipulation and optimization of process parameters.

Picturing the Gap Between the Performance and US-DOE's Hydrogen Storage Target: A Data-Driven Model for MgH2 Dehydrogenation.

Developing solid-state hydrogen storage materials is as pressing as ever, which requires a comprehensive understanding of the dehydrogenation chemistry of a solid-state hydride. Transition state search and kinetics calculations are essential to understanding and designing high-performance solid-state hydrogen storage materials by filling in the knowledge gap that current experimental techniques cannot measure. However, the ab initio analysis of these processes is computationally expensive and time-consuming. Searching for descriptors to accurately predict the energy barrier is urgently needed, to accelerate the prediction of hydrogen storage material properties and identify the opportunities and challenges in this field. Herein, we develop a data-driven model to describe and predict the dehydrogenation barriers of a typical solid-state hydrogen storage material, magnesium hydride (MgH2), based on the combination of the crystal Hamilton population orbital of Mg-H bond and the distance between atomic hydrogen. By deriving the distance energy ratio, this model elucidates the key chemistry of the reaction kinetics. All the parameters in this model can be directly calculated with significantly less computational cost than conventional transition state search, so that the dehydrogenation performance of hydrogen storage materials can be predicted efficiently. Finally, we found that this model leads to excellent agreement with typical experimental measurements reported to date and provides clear design guidelines on how to propel the performance of MgH2 closer to the target set by the United States Department of Energy (US-DOE).

Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling.

Pien Tze Huang (PZH), a class I nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Copper-Catalyzed Enantioconvergent Radical N-Alkylation of Diverse (Hetero)aromatic Amines.

The 3d transition metal-catalyzed enantioconvergent radical cross-coupling provides a powerful tool for chiral molecule synthesis. In the classic mechanism, the bond formation relies on the interaction between nucleophile-sequestered metal complexes and radicals, limiting the nucleophile scope to sterically uncongested ones. The coupling of sterically congested nucleophiles poses a significant challenge due to difficulties in transmetalation, restricting the reaction generality. Here, we describe a probable outer-sphere nucleophilic attack mechanism that circumvents the challenging transmetalation associated with sterically congested nucleophiles. This strategy enables a general copper-catalyzed enantioconvergent radical N-alkylation of aromatic amines with secondary/tertiary alkyl halides and exhibits catalyst-controlled stereoselectivity. It accommodates diverse aromatic amines, especially bulky secondary and primary ones to deliver value-added chiral amines (>110 examples). It is expected to inspire the coupling of more nucleophiles, particularly challenging sterically congested ones, and accelerate reaction generality.

Rejection Sensitivity and Reactive Aggression in Early Adults: The Mediating Role of Loneliness and Maladaptive Coping.

Reactive aggression is an aggressive response to a perceived threat or provocation. It has detrimental effects on individuals and society. Rejection sensitivity, a disposition that one tends to anxiously expect, readily perceive, and intensely react to social rejection, has been associated with reactive aggression. Considering that the mechanism underlying this link remains unclear, this study explores the mediating role of loneliness and maladaptive coping. Participants included 1104 early adults between the ages of 17-23 (Mage = 20.35, SD = 1.11, 33.6% men) in China who completed the Chinese version of the Tendency to Expect Rejection Scale, Loneliness Scale, Ways of Coping Questionnaire, and Reactive-Active Aggression Questionnaire. The serial mediation model revealed that loneliness and maladaptive coping independently mediated the association of rejection sensitivity with reactive aggression. More importantly, the chain mediating effect of "loneliness-maladaptive coping" also accounted for this link. The above findings contribute to a deeper understanding of the relationships among these factors and suggested that rejection sensitivity could positively be related to reactive aggression through loneliness and maladaptive coping.

The changes of neurogenesis in the hippocampal dentate gyrus of SAMP8 mice and the effects of acupuncture and moxibustion.

BACKGROUND: Influenced by the global aging population, the incidence of Alzheimer's disease (AD) has increased sharply. In addition to increasing ß-amyloid plaque deposition and tau tangle formation, neurogenesis dysfunction has recently been observed in AD. Therefore, promoting regeneration to improve neurogenesis and cognitive dysfunction can play an effective role in AD treatment. Acupuncture and moxibustion have been widely used in the clinical treatment of neurodegenerative diseases because of their outstanding advantages such as early, functional, and benign two-way adjustment. It is urgent to clarify the effectiveness, greenness, and safety of acupuncture and moxibustion in promoting neurogenesis in AD treatment. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice at various ages were used as experimental models to simulate the pathology and behaviors of AD mice. Behavioral experiments, immunohistochemistry, Western blot, and immunofluorescence experiments were used for comparison between different groups. RESULTS: Acupuncture and moxibustion could increase the number of PCNA+ DCX+ cells, Nissl bodies, and mature neurons in the hippocampal Dentate gyrus (DG) of SAMP8 mice, restore the hippocampal neurogenesis, delay the AD-related pathological presentation, and improve the learning and memory abilities of SAMP8 mice. CONCLUSION: The pathological process underlying AD and cognitive impairment were changed positively by improving the dysfunction of neurogenesis. This indicates the promising role of acupuncture and moxibustion in the prevention and treatment of AD.

Trophic level plays an enhanced role in shaping microbiota structure and assembly in lakes with decreased salinity on the Qinghai-Tibet and Inner Mongolia Plateaus.

Plateau lakes characterized by salinization and eutrophication are essential aquatic ecosystems. A myriad of microorganisms serve as crucial biological resources in plateau lakes and drive the elemental cycles of these ecosystems. Currently, there is a paucity of knowledge regarding the impacts of salinization and eutrophication dynamics on the microbiota in plateau lakes. Here, high-throughput sequencing of the 16S ribosomal RNA genes (V4 region) was used to characterize microbial community structure and assembly in plateau lakes with different salinities and trophic levels. Water samples were collected at 191 sites across 24 lakes on the Qinghai-Tibet and Inner Mongolia Plateaus in northern China. The results showed that high salinity considerably reduced microbial alpha-diversity and niche breadth while increasing within-group similarity among various lake types. High salinity additionally decreased the complexity of microbial networks and enhanced network robustness. The assembly of microbial communities was primarily governed by deterministic processes in high-salinity and eutrophic low-salinity lakes. At decreased salinity, trophic level played a leading role in shaping microbial community structure, and the ecological processes shifted from deterministic processes driven by high salinity to eutrophication-driven deterministic processes. The biomarkers also varied from taxa adapted to high-salinity environments (e.g., Nanoarchaeaeota, Rhodothermia) to those suited for living in freshwater and low-salinity habitats (e.g., Alphaproteobacteria, Actinobacteria). In the case of eutrophication, Actinobacteria, Chloroflexi, and Cyanobacteria became the dominant taxa. Our findings indicate that decreased salinity enables trophic level to play an enhanced role in shaping microbial community structure and assembly in plateau lakes. This study enriches our knowledge about the ecological impacts of salinization and eutrophication in plateau lakes.

Inhibition of PKM2 suppresses osteoclastogenesis and alleviates bone loss in mouse periodontitis.

BACKGROUND: Chronic periodontitis triggers an increase in osteoclastogenesis, with glycolysis playing a crucial role in this process. Pyruvate kinase M2 (PKM2) is a critical enzyme involved in glycolysis and pyruvate metabolism. Yet, the precise function of PKM2 in osteoclasts and their formation remains unclear and requires further investigation. METHODS: Bioinformatics was used to investigate critical biological processes in osteoclastogenesis. In vitro, osteoclastogenesis was analyzed using tartrate-resistant acid phosphatase (TRAP) staining, phalloidin staining, quantitative real­time PCR (RT-qPCR), and Western blotting. Small interfering RNA (siRNA) of PKM2 and Shikonin, a specific inhibitor of PKM2, were used to verify the role of PKM2 in osteoclastogenesis. The mouse model of periodontitis was used to assess the effect of shikonin on bone loss. Analyses included micro computed tomography, immunohistochemistry, flow cytometry, TRAP staining and HE staining. RESULTS: Bioinformatic analysis revealed a significant impact of glycolysis and pyruvate metabolism on osteoclastogenesis. Inhibition of PKM2 leads to a significant reduction in osteoclastogenesis. In vitro, co-culture of the heat-killed Porphyromonas gingivalis significantly promoted osteoclastogenesis, concomitant with an increased PKM2 expression in osteoclasts. Shikonin weakened the promoting effect of porphyromonas gingivalis on osteoclastogenesis. In vivo experiments demonstrated that inhibition of PKM2 by shikonin alleviated bone loss induced by periodontitis, suppressed excessive osteoclastogenesis in alveolar bone, and reduced tissue inflammation to some extent. CONCLUSION: PKM2 inhibition by shikonin, a specific inhibitor of this enzyme, attenuated osteoclastogenesis and bone resorption in periodontitis. Shikonin appears to be a promising therapeutic agent for treating periodontitis.

Compressed cerebellar functional connectome hierarchy in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an inherited movement disorder characterized by a progressive decline in motor coordination. Despite the extensive functional connectivity (FC) alterations reported in previous SCA3 studies in the cerebellum and cerebellar-cerebral pathways, the influence of these FC disturbances on the hierarchical organization of cerebellar functional regions remains unclear. Here, we compared 35 SCA3 patients with 48 age- and sex-matched healthy controls using a combination of voxel-based morphometry and resting-state functional magnetic resonance imaging to investigate whether cerebellar hierarchical organization is altered in SCA3. Utilizing connectome gradients, we identified the gradient axis of cerebellar hierarchical organization, spanning sensorimotor to transmodal (task-unfocused) regions. Compared to healthy controls, SCA3 patients showed a compressed hierarchical organization in the cerebellum at both voxel-level (p < .05, TFCE corrected) and network-level (p < .05, FDR corrected). This pattern was observed in both intra-cerebellar and cerebellar-cerebral gradients. We observed that decreased intra-cerebellar gradient scores in bilateral Crus I/II both negatively correlated with SARA scores (left/right Crus I/II: r = -.48/-.50, p = .04/.04, FDR corrected), while increased cerebellar-cerebral gradients scores in the vermis showed a positive correlation with disease duration (r = .48, p = .04, FDR corrected). Control analyses of cerebellar gray matter atrophy revealed that gradient alterations were associated with cerebellar volume loss. Further FC analysis showed increased functional connectivity in both unimodal and transmodal areas, potentially supporting the disrupted cerebellar functional hierarchy uncovered by the gradients. Our findings provide novel evidence regarding alterations in the cerebellar functional hierarchy in SCA3.

Probing the functional hotspots inside protein hydrophobic pockets by in situ photochemical trifluoromethylation and mass spectrometry.

Due to the complex high-order structures and interactions of proteins within an aqueous solution, a majority of chemical functionalizations happen on the hydrophilic sites of protein external surfaces which are naturally exposed to the solution. However, the hydrophobic pockets inside proteins are crucial for ligand binding and function as catalytic centers and transporting tunnels. Herein, we describe a reagent pre-organization and in situ photochemical trifluoromethylation strategy to profile the functional sites inside the hydrophobic pockets of native proteins. Unbiased mass spectrometry profiling was applied for the characterization of trifluoromethylated sites with high sensitivity. Native proteins including myoglobin, trypsin, haloalkane dehalogenase, and human serum albumin have been engaged in this mild photochemical process and substantial hydrophobic site-specific and structure-selective trifluoromethylation substitutes are obtained without significant interference to their bioactivity and structures. Sodium triflinate is the only reagent required to functionalize the unprotected proteins with wide pH-range tolerance and high biocompatibility. This "in-pocket" activation model provides a general strategy to modify the potential binding pockets and gain essential structural insights into the functional hotspots inside protein hydrophobic pockets.

Unraveling potential mechanism of different metal ions effect on anammox through big data analysis, molecular docking and molecular dynamics simulation.

Heavy metals (HMs) have been widely reported to pose an adverse effect on anaerobic ammonia oxidation (anammox) bacteria, yet the underlying mechanisms remain unclear. This study provides new insights into the potential mechanisms of interaction between HMs and functional enzymes through big date analysis, molecular docking and molecular dynamics simulation. The statistical analysis indicated that 10 mg/L Cu(II) and Cd(II) reduced nitrogen removal rate (NRR) by 85% and 43%, while 5 mg/L Fe(II) enhanced NRR by 29%. Additionally, the results of molecular simulations provided a microscopic interpretation for these macroscopic data. Molecular docking revealed that Hg(II) formed a distinctive binding site on ferritin, while other HMs resided at iron oxidation sites. Furthermore, HMs exhibited distinct binding sites on hydrazine dehydrogenase. Concurrently, the molecular dynamics simulation results further substantiated their capacity to form complexes. Cu(II) displayed the strongest binding affinity with ferritin for -1576 ± 79 kJ/mol in binding free energy calculation. Moreover, Cd(II) bound to ferritin and HDH for -1052.67 ± 58.49 kJ/mol, -290.02 ± 49.68 kJ/mol, respectively. This research addressed a crucial knowledge gap, shedding light on potential applications for remediating heavy metal-laden industrial wastewater.

Copper-Catalyzed Enantioselective C(sp3 )-SCF3 Coupling of Carbon-Centered Benzyl Radicals with (Me4 N)SCF3.

In contrast with the well-established C(sp2 )-SCF3 cross-coupling to forge the Ar-SCF3 bond, the corresponding enantioselective coupling of readily available alkyl electrophiles to forge chiral C(sp3 )-SCF3 bond has remained largely unexplored. We herein disclose a copper-catalyzed enantioselective radical C(sp3 )-SCF3 coupling of a range of secondary/tertiary benzyl radicals with the easily available (Me4 N)SCF3 reagent. The key to the success lies in the utilization of chiral phosphino-oxazoline-derived anionic N,N,P-ligands through tuning electronic and steric effects for the simultaneous control of the reaction initiation and enantioselectivity. This strategy can successfully realize two types of asymmetric radical reactions, including enantioconvergent C(sp3 )-SCF3 cross-coupling of racemic benzyl halides and three-component 1,2-carbotrifluoromethylthiolation of arylated alkenes under mild reaction conditions. It therefore provides a highly flexible platform for the rapid assembly of an array of enantioenriched SCF3 -containing molecules of interest in organic synthesis and medicinal chemistry.

Occurrence of BTX and PAHs in underground drinking water of coking contaminated sites: Linkage with altitude and health risk assessment by boiling-modified models.

The safety of underground drinking water has received widespread attention. However, few studies have focused on the occurrence and health risks of pollutants in underground drinking water of coking contaminated sites. In this study, the distribution characteristics, sources, and human health risks of benzene, toluene, xylene (BTX) and polycyclic aromatic hydrocarbons (PAHs) in underground drinking water from a typical coking contaminated site in Shanxi of China were investigated. The average concentrations of BTX and PAHs in coking plant (CP) were 5.1 and 4.8 times higher than those in residential area (RA), respectively. Toluene and Benzene were the main BTX, while Acenaphthene, Fluorene, and Pyrene were the main PAHs. Concentrations of BTX/PAHs were negatively correlated with altitude, revealing altitude might be an important geological factor influencing spatial distribution of BTX/PAHs. PMF model demonstrated that the BTX/PAHs pollution in RA mainly originated from coking industrial activities. Health risk assessments were conducted by a modified US EPA-based model, in which environmental concentrations were replaced by residual concentrations after boiling. Residual ratios of different BTX/PAHs were determined by boiling experiments to be 9.4-93.8 %. The average total carcinogenic risks after boiling were decreased from 2.6 × 10-6 to 1.4 × 10-6 for adults, and from 4.3 × 10-6 to 2.1 × 10-6 for children, suggesting boiling was an effective strategy to reduce the carcinogenic risks from BTX/PAHs, especially for ingestion pathway. Monte Carlo simulation results matched well with the calculated results, suggesting the uncertainty was acceptable and the risk assessment results were reliable. This study provided useful information for revealing the spatial distribution of BTX/PAHs in underground drinking water of coking contaminated sites, understanding their linkage with altitude, and also helped to more accurately evaluate the health risks by using the newly established boiling-modified models.

Maize requires Embryo defective27 for embryogenesis and seedling development.

The essential role of plastid translation in embryogenesis has been established in many plants, but a retrograde signal triggered by defective plastid translation machinery that may leads to embryogenesis arrest remains unknown. In this study, we characterized an embryo defective27 (emb27) mutant in maize (Zea mays), and cloning indicates that Emb27 encodes the plastid ribosomal protein S13. The null mutant emb27-1 conditions an emb phenotype with arrested embryogenesis; however, the leaky mutant emb27-2 exhibits normal embryogenesis but an albino seedling-lethal phenotype. The emb27-1/emb27-2 trans-heterozygotes display varying phenotypes from emb to normal seeds but albino seedlings. Analysis of the Emb27 transcription levels in these mutants revealed that the Emb27 expression level in the embryo corresponds with the phenotypic expression of the emb27 mutants. In the W22 genetic background, an Emb27 transcription level higher than 6% of the wild-type level renders normal embryogenesis, whereas lower than that arrests embryogenesis. Mutation of Emb27 reduces the level of plastid 16S rRNA and the accumulation of the plastid-encoded proteins. As a secondary effect, splicing of several plastid introns was impaired in emb27-1 and 2 other plastid translation-defective mutants, emb15 and emb16, suggesting that plastome-encoded factors are required for the splicing of these introns, such as Maturase K (MatK). Our results indicate that EMB27 is essential for plastid protein translation, embryogenesis, and seedling development in maize and reveal an expression threshold of Emb27 for maize embryogenesis.

18F-FAPI-04 Outperforms 18F-FDG PET/CT in Clinical Assessments of Patients with Pancreatic Adenocarcinoma.

Accurate diagnosis and staging are crucial for selecting treatment for patients with pancreatic ductal adenocarcinoma (PDAC). The desmoplastic responses associated with PDAC are often characterized by hypometabolism. Here, we investigated 18F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in evaluation of PDAC and compared the findings with those obtained using 18F-FDG. Methods: Sixty-two PDAC patients underwent 18F-FAPI-04 PET/CT and 18F-FDG PET/CT. Identification of primary lesions, lymph node (LN) metastasis, and distant metastasis (DM) by these methods was evaluated, and TNM staging was performed. Correlation between SUVmax of the primary lesion and treatment response was explored in patients who received systemic therapy. Results: 18F-FAPI-04 PET/CT identified all patients with PDAC; 18F-FDG PET/CT missed 1 patient. Tracer uptake was higher in 18F-FAPI-04 PET/CT than in 18F-FDG PET/CT in primary tumors (10.63 vs. 2.87, P < 0.0001), LN metastasis (2.90 vs. 1.43, P < 0.0001), and DM (liver, 6.11 vs. 3.10, P = 0.002; peritoneal, 4.70 vs. 2.08, P = 0.015). The methods showed no significant difference in the T staging category, but the N and M values were significantly higher for 18F-FAPI-04 PET/CT than for 18F-FDG PET/CT (P = 0.002 and 0.008, respectively). Thus, 14 patients were upgraded, and only 1 patient was downgraded, by 18F-FAPI-04 PET/CT compared with 18F-FDG PET/CT. A high SUVmax of the primary tumor did not correlate with treatment response for either 18F-FAPI-04 or 18F-FDG. Conclusion: 18F-FAPI-04 PET/CT performed better than 18F-FDG PET/CT in identification of primary tumors, LN metastasis, and DM and in TNM staging of PDAC.