Bioconversion of agriculture by-products with functionally enhanced Streptomyces sp. SCUT-3: Fish skin as a model.

With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion.

The Effectiveness of Temporary Hemiepiphysiodesis for Non-idiopathic Coronal Angular Deformity of the Knee in Children: A Comparison of Hinge Eight-Plate and Traditional Eight-Plate.

OBJECTIVE: Temporary hemiepiphysiodesis (TH) is a very common technique for coronal angular deformity of the knee in children, especially non-idiopathic. However, there is currently a dearth of comparative research on the hinge eight-plate (HEP) and traditional eight-plate (TEP). This study aimed to assess the clinical effectiveness and implant-related complication rates of TH using TEP and HEP for non-idiopathic coronal angular deformity, as well as to identify clinical factors affecting correction velocity. METHODS: We retrospectively observed a consecutive series of patients with non-idiopathic coronal angular deformity of the knee who underwent TH using HEP or TEP and completed the deformity correction process from July 2016 to July 2022. According to the kind of eight plates, we divided those patients into the HEP group and the TEP treatment group. Relevant clinical factors, including the mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), screw divergence angle (SDA), angle of plate and screw (APS), hinge angle of HEP (HA), and the knee zone location of the lower extremity mechanical axis, were documented. Additionally, deformity correction velocity, complications, and clinical efficacy were assessed. Categorical variables were analyzed using the chi-squared test, Fisher exact test, or Wilcoxon test, while continuous variables were evaluated using the t-test or analysis of variance (ANOVA). RESULTS: There were 29 patients in the HEP treatment group (seven girls and 22 boys) and 33 patients (12 girls and 21 boys) in the TEP treatment group. In all, 91.86% (79/86 knees) of the genu angular deformities were completely corrected, 6.98% (6/86 knees) had the overcorrection condition, and 10.47% (9/86 knees) had screw loosening. The swayback HEP rate was 11.29% (7/62 HEPs), which was related to the screw loosening in the HEP group (p < 0.001). The overall correction velocities and screw divergence angle change speeds in the HEP group were all significantly faster than those in the TEP group (p < 0.05). The initial APS of the HEP implanted was higher than that of TEP (p < 0.01), and multisite changes of APS during deformity correction of the HEP group were smaller than that of the TEP group. CONCLUSION: HEP proved to be an appropriate device for TH for non-idiopathic coronal angular deformities of the knee with high correction velocity in children. Avoiding the occurrence of the swayback phenomenon may reduce the complications of HEP.

Novel approach for ameliorating high-fat diet-induced syndromes via probiotic-fermented oyster mushroom: from metabolites and microbiota to regulation mechanisms.

The potential effects of probiotics on lowering lipid accumulation and alleviating gut microbiota perturbation have been extensively substantiated, but whether Lactobacillus rhamnoses-fermented oyster mushroom (FOM) could more pronouncedly attenuate obesity remains unclear. In this study, the anti-obesity effect of FOM was estimated based on the gut microbiota profile and analysis of hepatic lipid metabolic characteristics. The results revealed that FOM intervention dramatically improved hepatic lipid accumulation, characterized by reduction in fat-related factor metabolism levels and liver lesion enzymatic activities and down-regulation of the expression of genes associated with glycolipid metabolism (Foxo1, Gck, G6pd, Il6r and IL-ß). Metabolomics analysis indicated HFD-induced dysglycaemia and disturbed amino acid metabolism, characterized by significant enrichment of pathways (butanoate metabolism, arginine biosynthesis, etc.) and elevated levels of D-mannose, succinate and ß-D-fructose, followed by a decreased galactitol content. Furthermore, FOM intervention showed significant enrichment of specific pathways, particularly transcriptional misregulation in cancer and FoxO signaling pathways, while the MAPK signaling pathway demonstrated consistent enrichment across all experimental groups. FOM intervention reshaped the gut microbiota structure by facilitating the proliferation of SCFA producers (Romboutsia, Ruminococcaceae and Allobaculum), together with the depletion of Lachnospiraceae population. The current study strengthened our understanding of FOM prebiotic activities and obesity alleviation mechanisms.

Media Literacy and Its Potential Influence on Mpox-Related Perceptions and Prevention Intentions in China During the 2022 Multi-Country Outbreak of Mpox.

Media literacy plays an increasingly important role in health communication during public health emergencies. The present study aimed to investigate the level of media literacy and its association with disease perceptions and behavioral intentions of receiving vaccination services among young men who have sex with men (YMSM) in China during the 2022 multi-country mpox outbreak. The data were from a large-scale cross-sectional survey conducted among 2,493 YMSM aged 18-29 years in six provincial regions in China in September 2022. A total of 2,079 YMSM who had obtained mpox information from social media platforms were included in this study. Correlation analysis and path analysis were conducted. The mean age of the sample was 24.7. After controlling for background variables, significant positive correlations were found in several pairs between media literacy, mpox-related perceptions (including perceived susceptibility to mpox, perceived severity of mpox, perceived benefits of mpox vaccination, and self-efficacy of receiving mpox vaccination), and the behavioral intention of receiving mpox vaccination. The mpox-related perceptions played a significant mediation role in the association between media literacy and intention of receiving mpox vaccination (indirect effect = 0.165, p < .001, effect size = 82.1%). Media literacy is crucial for developing disease perceptions during public health emergencies and may further influence the adoption of preventive measures. As social media platforms have become the main battle field of health communication during disease outbreaks, improvement of media literacy is urgently warranted.

An intrusion detection model to detect zero-day attacks in unseen data using machine learning.

In an era marked by pervasive digital connectivity, cybersecurity concerns have escalated. The rapid evolution of technology has led to a spectrum of cyber threats, including sophisticated zero-day attacks. This research addresses the challenge of existing intrusion detection systems in identifying zero-day attacks using the CIC-MalMem-2022 dataset and autoencoders for anomaly detection. The trained autoencoder is integrated with XGBoost and Random Forest, resulting in the models XGBoost-AE and Random Forest-AE. The study demonstrates that incorporating an anomaly detector into traditional models significantly enhances performance. The Random Forest-AE model achieved 100% accuracy, precision, recall, F1 score, and Matthews Correlation Coefficient (MCC), outperforming the methods proposed by Balasubramanian et al., Khan, Mezina et al., Smith et al., and Dener et al. When tested on unseen data, the Random Forest-AE model achieved an accuracy of 99.9892%, precision of 100%, recall of 99.9803%, F1 score of 99.9901%, and MCC of 99.8313%. This research highlights the effectiveness of the proposed model in maintaining high accuracy even with previously unseen data.

Correlative analysis of transcriptome and 16S rDNA in Procambarus clarkii reveals key signaling pathways are involved in Chlorantraniliprole stress response by phosphoinositide 3-kinase (PI3K).

Chlorantraniliprole (CAP), a diamide insecticide, is extensively used in agricultural production. With the increasing adoption of the rice-crayfish integrated farming model, pesticide application has become more frequent. However, the potential risk of CAP to crayfish (Procambarus clarkii) remains unclear. In this study, crayfish were exposed to 30, 60, 90 mg/L CAP for 96 h. As CAP exposure time and concentration increased, crayfish survival rates and total hemocyte counts (THC) decreased. Biochemical indicators revealed that CAP exposure induced oxidative stress and immunosuppression in crayfish, leading to metabolic disorders and reduced ATP content. Additionally, pathological analysis and 16S rDNA sequencing demonstrated that CAP exposure compromised the intestinal barrier of crayfish, altered the intestinal microbial community structure, and caused apoptosis. Differential gene expression analysis showed that CAP exposure significantly suppressed the expression of genes related to immune and energy metabolism pathways, resulting in immune dysfunction and insufficient energy supply, while activating the PI3K/AKT/mTOR signaling pathway. PI3K knockdown reduced antioxidant and digestive activities, increased the expression of proinflammatory and apoptosis genes, and exacerbated CAP-induced intestinal toxicity. This study is the first to explore the characterization and function of PI3K in crustaceans, providing new insights for further research on crustacean antioxidants and defense mechanisms.

Causal associations between intermediate very-low-density lipoprotein cholesterol-to-total lipids ratio and peptic ulcer: A bidirectional Mendelian randomization study.

BACKGROUND: Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) and the occurrence of peptic ulcers (PU). However, the precise causal relationship between these factors remains ambiguous. Consequently, this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer. AIM: To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) association with PU via genetic methods, guiding future clinical research. METHODS: Genome-wide association study (GWAS) datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project (https://gwas.mrcieu.ac.uk). For the forward Mendelian randomization (MR) analysis, 72 single nucleotide polymorphisms (SNPs) were identified as instrumental variables. These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL, with peptic ulcer as the outcome variable. Conversely, for the inverse MR analysis, no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome. All MR analyses utilized inverse variance weighted (IVW) as the primary analytical method. Additionally, weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects. Egger regression was used as a supplementary method to evaluate potential directional pleiotropy. Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing. RESULTS: The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer (IVW: OR = 2.557, 95%CI = 1.274-5.132, P = 0.008). However, no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis. CONCLUSION: In conclusion, our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers. However, further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.

The role of m6A-associated membraneless organelles in the RNA metabolism processes and human diseases.

N6-methyladenosine (m6A) is the most abundant post-transcriptional dynamic RNA modification process in eukaryotes, extensively implicated in cellular growth, embryonic development and immune homeostasis. One of the most profound biological functions of m6A is to regulate RNA metabolism, thereby determining the fate of RNA. Notably, the regulation of m6A-mediated organized RNA metabolism critically relies on the assembly of membraneless organelles (MLOs) in both the nucleus and cytoplasm, such as nuclear speckles, stress granules and processing bodies. In addition, m6A-associated MLOs exert a pivotal role in governing diverse RNA metabolic processes encompassing transcription, splicing, transport, decay and translation. However, emerging evidence suggests that dysregulated m6A levels contribute to the formation of pathological condensates in a range of human diseases, including tumorigenesis, reproductive diseases, neurological diseases and respiratory diseases. To date, the molecular mechanism by which m6A regulates the aggregation of biomolecular condensates associated with RNA metabolism is unclear. In this review, we comprehensively summarize the updated biochemical processes of m6A-associated MLOs, particularly focusing on their impact on RNA metabolism and their pivotal role in disease development and related biological mechanisms. Furthermore, we propose that m6A-associated MLOs could serve as predictive markers for disease progression and potential drug targets in the future.

Transcriptome analysis provides new insight into the mechanism of Bombyx mori under zinc exposure.

Zinc is a significant source of heavy metal pollution that poses risks to both human health and biodiversity. Excessive concentrations of zinc can hinder the growth and development of insects and trigger cell death through oxidative damage. The midgut is the main organ affected by exposure to heavy metals. The silkworm, a prominent insect species belonging to the Lepidoptera class and widely used in China, serves as a model for studying the genetic response to heavy metal stress. In this study, high-throughput sequencing technology was employed to investigate detoxification-related genes in the midgut that are induced by zinc exposure. A total of 11,320 unigenes and 14,723 transcripts were identified, with 553 differentially expressed genes (DEGs) detected, among which 394 were up-regulated and 159 were down-regulated. The Gene Ontology (GO) analysis revealed that 452 DEGs were involved in 18 biological process subclasses, 14 cellular component subclasses and 8 molecular functional subclasses. Furthermore, the KEGG analysis demonstrated enrichment in pathways such as Protein digestion, absorption and Lysosome. Validation of the expression levels of 9 detoxification-related DEGs through qRT-PCR confirmed the accuracy of the RNA-seq results. This study not only contributes new insights into the detoxification mechanisms mechanism of silkworms against zinc contamination, but also serves as a foundation basis for understanding the molecular detoxification processes in lepidopteran insects.

Ferritin Heavy-like subunit is involved in the innate immune defense of the red swamp crayfish Procambarus clarkii.

Iron-binding proteins, known as ferritins, play pivotal roles in immunological response, detoxification, and iron storage. Despite their significance to organisms, little is known about how they affect the immunological system of the red swamp crayfish (Procambarus clarkii). In our previous research, one ferritin subunit was completely discovered as an H-like subunit (PcFeH) from P. clarkii. The full-length cDNA of PcFerH is 1779 bp, including a 5'-UTR (untranslated region, UTR) of 89 bp, 3'-UTR (untranslated region, UTR) of 1180 bp and an ORF (open reading frame, ORF) of 510 bp encoding a polypeptide of 169 amino acids that contains a signal peptide and a Ferritin domain. The deduced PcFerH protein sequence has highly identity with other crayfish. PcFerH protein's estimated tertiary structure is quite comparable to animal structure. The PcFerH is close to Cherax quadricarinatus, according to phylogenetic analysis. All the organs examined showed widespread expression of PcFerH mRNA, with the ovary exhibiting the highest levels of expression. Additionally, in crayfish muscles, intestines, and gills, the mRNA transcript of PcFerH was noticeably up-regulated, after LPS and Poly I:C challenge. The expression of downstream genes in the immunological signaling system was suppressed when the PcFerH gene was knocked down. All of these findings suggested that PcFerH played a vital role in regulating the expression of downstream effectors in the immunological signaling pathway of crayfish.

Transcriptomic analysis provides insights into the immune responsive genes in the Procambarus clarkii hepatopancreas challenged with Vibrio parahaemolyticus.

Procambarus clarkii is an economically important species in China; however, its high mortality rate due to pathogenic bacteria, particularly Vibrio parahaemolyticus, results in significant economic loss. This study aimed to understand the immune response of crayfish to bacterial infection by comparing and analyzing transcriptome data of hepatopancreatic tissue from P. clarkii challenged with V. parahaemolyticus or treated with PBS. Physiological indices (TP, Alb, ACP, and AKP) were analyzed, and tissue sections were prepared. After assembling and annotating the data, 18,756 unigenes were identified. A comparison of the expression levels of these unigenes between the control and V. parahaemolyticus groups revealed 4037 DEGs, with 2278 unigenes upregulated and 1759 downregulated in the V. parahaemolyticus group. GO (Gene Ontology) enrichment analysis shows that the DGEs are mainly enriched in cellular anatomical activity, bindinga and cellular process, enrichment analysis of KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways showed that DGEs were mainly enriched in Base excision repair, Phagosome and Longevity regulating pathway. At the same time, lysosome was also enriched. The phagosome and lysosome pathways play a crucial role in the immune defense of crayfish against V. parahaemolyticus injection that will be highlighted. In addition, the expression levels of six selected immune-related DEGs were measured using qRT-PCR, which validated the results of RNA-seq analysis. This study provides a new perspective on the immune system and defense mechanisms of P. clarkii and a valuable foundation for further investigation of the molecular immune mechanisms of this species.

Correction: Attenuation of metabolic syndrome in the ob/ob mouse model by resistant starch intervention is dose dependent.

Correction for 'Attenuation of metabolic syndrome in the ob/ob mouse model by resistant starch intervention is dose dependent' by Anqi Wang et al., Food Funct., 2019, 10, 7940-7951, https://doi.org/10.1039/C9FO01771B.

Insights into chlorantraniliprole exposure via activating cytochrome P450-mediated xenobiotic metabolism pathway in the Procambarus clarkii: Identification of P450 genes involved in detoxification.

To investigate the impact of chlorantraniliprole on Procambarus clarkii, acute toxicity tests were performed. Results indicated that 96 h post-exposure to chlorantraniliprole (60 mg/L) led to the separation of the hepatopancreas basement membrane, causing cell swelling, rupture, and vacuolation. Moreover, acid phosphatase (ACP) and alkaline phosphatase (AKP) activities exhibited divergent trends across four concentrations of chlorantraniliprole (0, 30, 60, and 90 mg/L). Hydrogen peroxide (H2O2) and catalase (CAT) levels significantly increased, while total superoxide dismutase (T-SOD) and malonaldehyde (MDA) activities decreased, indicating oxidative stress in the hepatopancreas. A total of 276 differentially expressed genes (DEGs) were identified, with 204 up-regulated and 72 down-regulated. Out of these, 114 DEGs were successfully annotated and classified into 99 pathways, with a primary focus on the cytochrome P450-mediated xenobiotic metabolism pathway. The DEGs enriched in this pathway, along with transcriptome data, were validated using quantitative-polymerase chain reaction. This study enhances the transcriptome database of P. clarkii and provides fundamental insights into its immune defense and antioxidant mechanisms. Additionally, it lays a theoretical foundation for future research on disease prevention in P. clarkii within rice-shrimp culture systems.

Depressive symptoms and its multifaceted associated factors among young men who have sex with men facing the dual threats of COVID-19 and mpox in China.

INTRODUCTION: The COVID-19 pandemic has significantly impacted the mental health of human beings since 2020, especially the young people and the pre-existing marginalized groups such as men who have sex with men (MSM). During the COVID-19 pandemic, the multi-country outbreak of mpox in 2022 additionally posed a significant stress on the most-affected communities (i.e., MSM). This study investigated the level of depressive symptoms and its multifaceted associated factors among Chinese young men who have sex with men (YMSM) in this unique period. METHODS: In September 2022, a large-scale cross-sectional survey was conducted among YMSM aged 18-29 years across six representative provinces in China. Hierarchical regression analysis was performed to test the various types of associated factors of depressive symptoms. RESULTS: Among the 2493 participants, 65.6 % (n = 1638) reported mild to severe depressive symptoms. The hierarchical regression analysis identified that depressive symptoms was significantly positively associated with unemployment, having substance use in the past 6 months, a higher level of MSM self-stigma, incompletion of COVID-19 vaccination, greater mpox risk perception, and presence of mpox related-like symptoms. LIMITATIONS: This study used the facility-based sampling method to recruit the participants, which may lead to selection bias. CONCLUSIONS: Chinese YMSM faced significant mental health challenges during the concurrent epidemics of COVID-19 and mpox, which was associated with their socio-economic status, risk behaviors, stigma, and multiple diseases-related variables. Proactive measures may hold promise as effective strategies for mitigating mental distress among marginalized groups during public health crises.

Effects of tea infusion on selenium uptake in grapevine.

Increased selenium (Se) content in fruits can supply Se in human body, but the effects of teas on the Se uptake in fruit trees are unknown. The effects of infusions of four teas (green, black, dark, and white) on the Se uptake of grapevine were studied to promote the Se uptake in fruit trees in this study. However, only black tea infusion increased the biomass, photosynthetic pigment content, superoxide dismutase (SOD) activity, peroxidase (POD) activity, and soluble protein content of grapevine. Except for white tea infusion, other tea infusions also increased the catalase (CAT) activity of grapevine. Furthermore, the tea infusions increased the activities of adenosine triphosphate sulfurase (ATPS) and adenosine 5'-phosphosulfate reductase (APR), and decreased the activities of serine acetyltransferase (SAT) and selenocysteine methyltransferase (SMT). Only the dark and white tea infusions increased the shoot total Se content by 86.53% and 23.32%, respectively (compared with the control), and also increased the shoot inorganic Se content and shoot organic Se content. Notably, four tea infusions decreased the organic Se proportion and increased the inorganic Se proportion in grapevine. Correlation and grey relational analyses showed that the root total Se content, ATPS activity, and ARP activity were closely associated with the shoot total Se content. The principal component and cluster analyses also showed that the ATPS activity, APR activity, root total Se content, and shoot total Se content were classified into one category. These findings show that black tea infusion can promote grapevine growth, while dark and white tea infusions can promote the Se uptake in grapevine.

Antibiotic resistance characterization, virulence factors and molecular characteristics of Bacillus species isolated from probiotic preparations in China.

OBJECTIVES: The aim of this study was to determine the phenotypic and molecular characteristics of antibiotic-resistant Bacillus spp. isolated from probiotic preparations in China. METHODS: Bacillus strains were isolated from probiotic preparations and then identified using 16S rDNA sequencing. Drug sensitivity tests were conducted to determine their susceptibility to seven antibiotics. Whole genome sequencing was performed on the most resistant strains, followed by analysis of their molecular characteristics, resistance genes, and virulence factors. RESULTS: In total, we isolated 21 suspected Bacillus species from seven compound probiotics, which were identified by 16S rDNA as 12 Bacillus licheniformis, six Bacillus subtilis and three Bacillus cereus. The determination of antimicrobial susceptibility showed widespread resistance to chloramphenicol (95.2%), erythromycin (85.7%) and gentamicin (42.9%). Whole genome sequencing of seven resistant strains revealed that J-6-A (Bacillus subtilis) and J-7-A (Bacillus cereus) contained a plasmid. The resistance gene analysis revealed that each strain contained more than ten resistance genes, among which J-7-A was the most. The streptomycin resistance gene strA was detected in all strains. The chloramphenicol resistance genes ykkC and ykkD were found in J-1-A to J-5-A and were first reported in Bacillus subtilis. The erythrocin resistance gene ermD was detected in strains J-1-A to J-4-A. There were also more than 15 virulence factors and gene islands (GIs) involved in each strain. CONCLUSIONS: These results confirm the potential safety risks of probiotics and remind us to carefully select probiotic preparations containing strains of Bacillus species, especially Bacillus cereus, to avoid the potential spread of resistance and pathogenicity.

Designer cellular spheroids with DNA origami for drug screening.

Current in vitro models struggle to balance the complexity of human diseases with suitability for large-scale drug tests. While 3D cultures simulate human tissues, they lack cellular intricacy, and integrating these models with high-throughput drug screening remains a challenge. Here, we introduce a method that uses self-assembling nucleic acid nanostructures decorated living cells, termed NACs, to create spheroids with a customizable 3D layout. To demonstrate its uniqueness, our method effectively creates designer 3D spheroids by combining parenchymal cells, stromal cells, and immune cells, leading to heightened physiological relevance and detailed modeling of complex chronic diseases and immune-stromal interactions. Our approach achieves a high level of biological fidelity while being standardized and straightforward to construct with the potential for large-scale drug discovery applications. By merging the precision of DNA nanotechnology with advanced cell culture techniques, we are streamlining human-centric models, striking a balance between complexity and standardization, to boost drug screening efficiency.

Chemoselective Silver-Catalyzed Nitrene Transfer: Tunable Syntheses of Azepines and Cyclic Carbamimidates.

Azepines and their saturated azepane counterparts are important moieties in bioactive molecules but are under-represented in current drug screening libraries. Herein, we report a mild and efficient azepine formation via silver-catalyzed dearomative nitrene transfer. A 2,2,2-trichloroethoxysulfonyl (Tces)-protected carbamimidate nitrene precursor, coupled with the appropriate ligand for silver, is essential for achieving the unexpected chemoselectivity between arene dearomatization and benzylic C(sp3)-H amination. Potential applications in the late-stage diversification of azepines to complex molecular scaffolds and diastereoselective hydrogenations to sp3-rich derivatives are also highlighted.

Effects of different rootstocks grafting on selenium accumulation in Cyphomandra betacea Sendt. seedlings under selenium-contaminated soil.

The effects of rootstocks tomato (Solanum lycopersicum L.), eggplant (Solanum melongena L.), and nightshade (Solanum nigrum L.) grafting on the growth and selenium (Se) accumulation of Cyphomandra betacea Sendt. seedlings were studied to identify the most suitable rootstock for increasing Se uptake of fruit trees grown in Se-contaminated soil. The rootstocks of tomato, eggplant, and nightshade grafting increased the scion biomass of C. betacea seedlings by 146.1%, 23.2%, and 94.5%, respectively, compared with the un-grafted seedlings. Moreover, tomato, eggplant, and nightshade rootstocks grafting increased the photosynthesis, superoxide dismutase activity, and peroxidase activity, while reducing the catalase activity and soluble protein content of C. betacea seedlings. Although all three rootstocks grafting decreased Se contents in rootstock roots and stems, only nightshade rootstock grafting increased Se content in the scions of C. betacea seedlings. Notably, root biomass, catalase activity, soluble protein content, rootstock root Se content, and rootstock stem Se content were closely related to the scion Se content. These findings suggest that only grafting onto nightshade rootstock significantly enhances Se uptake in C. betacea, whereas tomato and eggplant rootstocks grafting have no effect on Se uptake.

This study shows that under selenium (Se)-contaminated soil conditions, tomato, eggplant, and nightshade rootstocks can promote the growth of C. betacea seedlings and improve their stress resistance. The nightshade rootstock stands out for its ability to promote Se uptake in C. betacea seedlings, suggesting its suitability as a promising rootstock to enhance both growth and Se uptake in C. betacea.

Identification and Validation of PKR as a Direct Target for the Novel Sulfonamide-Substituted Tetrahydroquinoline Nonselective Inhibitor of the NLRP3 Inflammasome.

The NLRP3 inflammasome is a critical component of the innate immune system. The persistent abnormal activation of the NLRP3 inflammasome is implicated in numerous human diseases. Herein, sulfonamide-substituted tetrahydroquinoline derivative S-9 was identified as the most promising NLRP3 inhibitor, without obvious cytotoxicity. In vitro, S-9 inhibited the priming and activation stages of the NLRP3 inflammasome. Incidentally, we also observed that S-9 had inhibitory effects on the NLRC4 and AIM2 inflammasomes. To elucidate the multiple anti-inflammatory activities of S-9, photoaffinity probe P-2, which contained a photoaffinity label and a functional handle, was developed for target identification by chemical proteomics. We identified PKR as a novel target of S-9 in addition to NLRP3 by target fishing. Furthermore, S-9 exhibited a significant anti-neuroinflammatory effect in vivo. In summary, our findings show that S-9 is a promising lead compound targeting both PKR and NLRP3 that could emerge as a molecular tool for treating inflammasome-related diseases.