Discovery of seed germinating fungi (Mycetinis scorodonius) from Gastrodia elata Bl. f. glauca S. chow in Changbai Mountain and examination of their germination ability.

Multi-generational asexual reproduction of Gastrodia elata Bl. will cause seedling species degeneration. Sexual reproduction of Gastrodia elata Bl. seed is an effective method to solve the problem of degeneration. The development of Gastrodia elata Bl. seeds cannot be separated from the germination fungus. However, there are few strains of germination fungus in production, and there is also the problem of species degradation in application for many years. It is very important for the sexual reproduction of Gastrodia elata Bl. to isolate more new strains of excellent germination fungus from the origin. This study used the Gastrodia elata Bl. f. glauca S. chow seeds germination vegetative propagation corms capture method to isolate its symbiotic germination fungus, and comprehensively identified the species of germination fungus by colony morphology, ITS, sporocarps regeneration and germination function, and compared the growth characteristics and germination ability with other germination fungus (Mycena purpureofusca, Mycena dendrobii and Mycena osmundicola). The germination fungus was isolated from the vegetative propagation corms of Gastrodia elata Bl. f. glauca S. chow seeds and named GYGL-1. After comprehensive identification, GYGL-1 was Mycetinis scorodonius. Compared with other germination fungus, GYGL-1 has fast germination speed, vigorous growth, and high germination ability for Gastrodia elata Bl. f. glauca S. chow seeds. Innovated the isolation method of Gastrodia elata Bl. seeds germination fungus, obtained the regenerated sporocarps of the germination fungus, and discovered that Mycetinis scorodonius has a new function of germinating Gastrodia elata Bl. f. glauca S. chow seeds, enriching the resource library of Gastrodia elata Bl. germination fungus.

Molecular Mechanism of Yangshen Maidong Decoction in the Treatment of Chronic Heart Failure based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

Chronic heart failure (CHF) is a complex multifactorial clinical syndrome leading to abnormal cardiac structure and function. The severe form of this ailment is characterized by high disability, high mortality, and morbidity. Worldwide, 2-17% of patients die at first admission, of which 17-45% die within 1 year of admission and >50% within 5 years. Yangshen Maidong Decoction (YSMDD) is frequently used to treat the deficiency and pain of the heart. The specific mechanism of action of YSMDD in treating CHF, however, remains unclear. Therefore, a network pharmacology-based strategy combined with molecular docking and molecular dynamics simulations was employed to investigate the potential molecular mechanism of YSMDD against CHF. The effective components and their targets of YSMDD and related targets of CHF were predicted and screened based on the public database. The network pharmacology was used to explore the potential targets and possible pathways that involved in YSMDD treated CHF. Molecular docking and molecular dynamics simulations were performed to elucidate the binding affinity between the YSMDD and CHF targets. Screen results, 10 main active ingredients, and 6 key targets were acquired through network pharmacology analysis. Pathway enrichment analysis showed that intersectional targets associated pathways were enriched in the Prostate cancer pathway, Hepatitis B pathway, and C-type lectin receptor signaling pathways. Molecular docking and molecular dynamics simulations analysis suggested 5 critical active ingredients have high binding affinity to the 5 key targets. This research shows the multiple active components and molecular mechanisms of YSMDD in the treatment of CHF and offers resources and suggestions for future studies.

Molecular mechanism of trehalose 6-phosphate inhibition of the plant metabolic sensor kinase SnRK1.

SUCROSE-NON-FERMENTING1-RELATED PROTEIN KINASE1 (SnRK1), a central plant metabolic sensor kinase, phosphorylates its target proteins, triggering a global shift from anabolism to catabolism. Molecular modeling revealed that upon binding of KIN10 to GEMINIVIRUS REP-INTERACTING KINASE1 (GRIK1), KIN10's activation T-loop reorients into GRIK1's active site, enabling its phosphorylation and activation. Trehalose 6-phosphate (T6P) is a proxy for cellular sugar status and a potent inhibitor of SnRK1. T6P binds to KIN10, a SnRK1 catalytic subunit, weakening its affinity for GRIK1. Here, we investigate the molecular details of T6P inhibition of KIN10. Molecular dynamics simulations and in vitro phosphorylation assays identified and validated the T6P binding site on KIN10. Under high-sugar conditions, T6P binds to KIN10, blocking the reorientation of its activation loop and preventing its phosphorylation and activation by GRIK1. Under these conditions, SnRK1 maintains only basal activity levels, minimizing phosphorylation of its target proteins, thereby facilitating a general shift from catabolism to anabolism.

Natural products as glycolytic inhibitors for cervical cancer treatment: A comprehensive review.

Cervical cancer, a prevalent gynaecological malignancy, presents challenges in late-stage treatment efficacy. Aerobic glycolysis, a prominent metabolic trait in cervical cancer, emerges as a promising target for novel drug discovery. Natural products, originating from traditional medicine, represent a significant therapeutic avenue and primary source for new drug development. This review explores the regulatory mechanisms of glycolysis in cervical cancer and summarises natural compounds that inhibit aerobic glycolysis as a therapeutic strategy. The glycolytic phenotype in cervical cancer is regulated by classical molecules such as HIF-1, HPV virulence factors and specificity protein 1, which facilitate the Warburg effect in cervical cancer. Various natural products, such as artemisinin, shikonin and kaempferol, exert inhibitory effects by downregulating key glycolytic enzymes through signalling pathways such as PI3K/AKT/HIF-1α and JAK2/STAT3. Despite challenges related to drug metabolism and toxicity, these natural compounds provide novel insights and promising avenues for cervical cancer treatment.

The titers of antinuclear antibodies are associated with the degree of inflammation and organ damage in Primary Sjögren's Syndrome.

Primary Sjögren's Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage.

Crotonoids A-H, Labdane-Type Diterpenoids with Anti-Inflammatory Activity from Croton sublyratus.

Croton sublyratus (Euphorbiaceae) is a traditional medicinal plant used by the Thai populace to treat helminthic infections and dermatologic conditions. In present study, eight new labdane-type diterpenoids, crotonoids A-H (1-8) and one known analogue (9) were isolated from the aerial parts of C. sublyratus. Compounds 6 and 7 belong to the rare class of 14,15-dinor-labdane diterpenoids. Compound 8 exhibited a rare 14,15,17-trinor-labdane skeleton. The structures of all these diterpenoids were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Compound 9 exhibited moderate anti-inflammatory activity via the inhibition of NO production in lipopolysaccharide-induced RAW 264.7 cells.

A Knowledge-Driven Self-Supervised Approach for Molecular Generation.

Due to the great successes of Graph Neural Networks (GNN) in numerous fields, growing research interests have been devoted to applying GNN to molecular learning tasks. The molecule structure can be naturally represented as graphs where atoms and bonds refer to nodes and edges respectively. However, the atoms are not haphazardly stacked together but combined into various spatial geometries. Meanwhile, since chemical reactions mainly occur in substructures such as functional groups, the substructure plays a decisive role in the molecule's properties. Therefore, directly applying GNN to molecular representation learning could ignore the molecular spatial structure and the substructure properties which in turn degrades the performance of downstream tasks. In this paper, we propose Knowledge-Driven Self-Supervised Model for Molecular Representation Learning (KSMRL) to address above problems. The KSMRL consists of two major pathways: (1) the Spatial Information (SI) based pathway which preserves the spatial information of molecular structure, (2) the Subgraph Constraint (SC) based pathway which retains the properties of substructures into the molecular representation. In this manner, both the atomic level and substructure level information can be included in modeling. According to the experimental results on multiple datasets, the proposed KSMRL can generate discriminative molecular representations. In molecular generation tasks, KSMRL combined with Autoregressive Flow (AF) models or Discrete Flow (DF) models outperforms the state-of-the-art baselines over all datasets. In addition, we demonstrate the effectiveness of KSMRL with property optimization experiments. To indicate the ability of predicting specified potential Drug-Target Interactions (DTIs), a case study for discriminating the interactions between molecule generated by KSMRL and targets is also given.

Corydalis sunhangii (Papaveraceae): A new species from Xizang, China, based on plastome and morphological data.

A new species of Papaveraceae, Corydalis sunhangii, in the section Trachycarpae, is described and illustrated from Nyingchi City, Xizang, China. The new species has some resemblance to Corydalis kingdonis, but differs by radical leaves prominent, usually several, blade tripinnate (vs. insignificant, few, blade bi- to triternate); cauline leaf usually one, much smaller than radical leaves, usually situated in lower half of stem (vs. usually two, larger than radical leaves, concentrated in upper third of stem); racemes densely 13-35-flowered (vs. rather lax, 4-11-flowered); claw of lower petal shallowly saccate (vs. very prominently and deeply saccate); capsule oblong, with raised lines of dense papillae (vs. broadly obovoid, smooth). Phylogenetic analysis, based on 68 protein-coding plastid genes of 49 samples, shows that C. sunhangii is not closely related to any hitherto described species, which is consistent with our morphological analysis.

Utilization of the waste aqueous phase from tea residue hydrothermal carbonization for preparing active food packaging films.

Hydrothermal carbonization (HTC) is an effective strategy for high-value utilization of tea residue (TR), and it was noticed the aqueous phase (AP) has not been extensively studied. This study aimed to investigate the chemical components and characteristics of the AP, and applied it in active food packaging films. The results showed that the total phenolic content of AP was 1.86 mg GAE/mL, and the main compounds in AP were organic acids, alcohols, and amino acids. The AP showed excellent antibacterial activity and antioxidant capacity. The active films were prepared using the casting method. The 4:7-AP/PVA film showed outstanding mechanical properties (tensile strength = 34.18 MPa, elongation at break = 458.67%), antioxidant ability (DPPH scavenging capacity 92.01%), antibacterial activity, water resistance and biocompatibility. The banana preservation test showed the AP/PVA films could successfully prolong the shelf-life of bananas and have the potential to be food packaging films.

Anti-Inflammatory Salicin Derivatives from the Barks of Salix tetrasperma.

The genus Salix L. is traditionally used in folk medicine to alleviate pain caused by various kinds of inflammation. In the present study, 10 undescribed salicin derivatives along with 5 known congeners were isolated from the barks of Salix tetrasperma, and their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and chemical conversions. Compounds 4-6 significantly inhibited NO production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and the most active 4 obviously suppressed the production of IL-1ß and IL-6 and decreased iNOS and COX-2 expression in a dose-dependent manner. Further Western blotting analysis revealed that the anti-inflammatory mechanism of 4 is possibly mediated through the MAPK and NF-κB signaling pathways.

Anti-NSCLC role of SCN4B by negative regulation of the cGMP-PKG pathway: Integrated utilization of bioinformatics analysis and in vitro assay validation.

Non-small cell lung cancer (NSCLC) is a malignant tumor with low overall cure and survival rates. Uncovering abnormally expressed genes is significantly important for developing novel targeted therapies in NSCLC. This study aimed to discover new differentially expressed genes (DEGs) of NSCLC. The DEGs of NSCLC were identified in eight data sets from Gene Expression Omnibus (GEO) database. The expression profiles and the prognostic significance of SCN4B in LUAD and LUSC were analyzed using GEPIA database. LinkedOmics was used to identify co-expressed genes with SCN4B, which were further subjected to KEGG pathway enrichment analysis. SCN4B-overexpressing plasmid (pcDNA/SCN4B) was transfected into A549 and NCI-H2170 cells to elevate the expression of SCN4B. MTT and TUNEL assays were performed to evaluate cell viability and apoptosis. Relying on the screened DEGs from GEO database, we identified that SCN4B was significantly downregulated in LUAD and LUSC. We confirmed the downregulation of SCN4B in NSCLC tissues using GEPIA database. SCN4B has a prognostic value in LUAD, but not LUSC. KEGG pathway enrichment analysis of SCN4B-related genes showed that cGMP-PKG signaling pathway might be involved in the role of SCN4B in NSCLC. Overexpression of SCN4B in A549 and NCI-H2170 cells inhibited the cell viability. Besides, SCN4B overexpression induced apoptosis of A549 and NCI-H2170 cells. SCN4B inhibited the expression of PKG1 and p-CREB in NSCLC cells. Moreover, the inhibitory effects of SCN4B on tumor malignancy were attenuated by the activator of PKG. In conclusion, integrated bioinformatical analysis proved that SCN4B was downregulated and had a prognostic significance in NSCLC. In vitro experimental studies demonstrated that SCN4B regulated NSCLC cells viability and apoptosis via inhibiting cGMP-PKG signaling pathway.

Comparative chloroplast genomes of Dactylicapnos species: insights into phylogenetic relationships.

BACKGROUND: Dactylicapnos is a climbing herbaceous vine, distributed from the Himalayas to southwestern China, and some of the species have important medicinal values. However, the chloroplast genomes of Dactylicapnos have never been investigated. In this study, chloroplast genomes of seven Dactylicapnos species covering all three sections and one informal group of Dactylicapnos were sequenced and assembled, and the detailed comparative analyses of the chloroplast genome structure were provided for the first time. RESULTS: The results showed that the chloroplast genomes of Dactylicapnos have a typical quadripartite structure with lengths from 172,344 bp to 176,370 bp, encoding a total of 133-140 genes, containing 88-94 protein-coding genes, 8 rRNAs and 37-39 tRNAs. 31 codons were identified as relative synonymous codon usage values greater than one in the chloroplast genome of Dactylicapnos genus based on 80 protein-coding genes. The results of the phylogenetic analysis showed that seven Dactylicapnos species can be divided into three main categories. Phylogenetic analysis revealed that seven species form three major clades which should be treated as three sections. CONCLUSIONS: This study provides the initial report of the chloroplast genomes of Dactylicapnos, their structural variation, comparative genomic and phylogenetic analysis for the first time. The results provide important genetic information for development of medical resources, species identification, infrageneric classification and diversification of Dactylicapnos.

Nonionic polymer and amino acid-assisted synthesis of ZSM-5 nanocrystals and their catalytic application in the alkylation of 2-methylnaphthalene.

The synthesis of nanosized ZSM-5 zeolites with high crystallinity and suitable acidity is very significant for their great potential in various catalytic applications. Herein, a series of zeolite ZSM-5 crystals with different particle sizes and SiO2/Al2O3 ratios (10-30) were synthesized by a temperature-varying two-step crystallization method in a concentrated gel system containing L-lysine and/or polyvinylpyrrolidone (PVP) additives. By optimizing the addition amounts of the two additives, the crystal size of the ZSM-5 zeolite could be reduced to less than 100 nm. Meanwhile, relatively high crystallinity and framework Al incorporation rates could be achieved, resulting in the generation of high-quality ZSM-5 nanocrystals. The nanosized H-form ZSM-5 zeolite with a SiO2/Al2O3 ratio of 20 showed enhanced catalytic efficiency and stability for the alkylation of 2-methylnaphthalene (2-MN) with methanol to produce an important intermediate, 2,6-dimethylnaphthalene (2,6-DMN). A relatively high and steady yield of 2,6-DMN (above 7.2%) could be achieved during 20 h time-on-stream at 400 °C. The smaller crystal size, higher crystallinity and framework Al content could provide more accessible Brønsted acid sites in the 10-membered ring channel of the ZSM-5 nanocrystals, which are the main active sites responsible for the shape-selectivity of the targeted product of 2,6-DMN. As a result, the formation of other side products like 1-MN and poly-MN could be effectively inhibited, thus leading to an improved 2,6-DMN yield and coke resistance over the nanosized ZSM-5 catalyst.

Correlative single-cell hard X-ray computed tomography and X-ray fluorescence imaging.

X-ray computed tomography (XCT) and X-ray fluorescence (XRF) imaging are two non-invasive imaging techniques to study cellular structures and chemical element distributions, respectively. However, correlative X-ray computed tomography and fluorescence imaging for the same cell have yet to be routinely realized due to challenges in sample preparation and X-ray radiation damage. Here we report an integrated experimental and computational workflow for achieving correlative multi-modality X-ray imaging of a single cell. The method consists of the preparation of radiation-resistant single-cell samples using live-cell imaging-assisted chemical fixation and freeze-drying procedures, targeting and labeling cells for correlative XCT and XRF measurement, and computational reconstruction of the correlative and multi-modality images. With XCT, cellular structures including the overall structure and intracellular organelles are visualized, while XRF imaging reveals the distribution of multiple chemical elements within the same cell. Our correlative method demonstrates the feasibility and broad applicability of using X-rays to understand cellular structures and the roles of chemical elements and related proteins in signaling and other biological processes.

Iron Stress Affects the Growth and Differentiation of Toxoplasma gondii.

Iron is an indispensable nutrient for the survival of Toxoplasma gondii; however, excessive amounts can lead to toxicity. The parasite must overcome the host's "nutritional immunity" barrier and compete with the host for iron. Since T. gondii can infect most nucleated cells, it encounters increased iron stress during parasitism. This study assessed the impact of iron stress, encompassing both iron depletion and iron accumulation, on the growth of T. gondii. Iron accumulation disrupted the redox balance of T. gondii while enhancing the parasite's ability to adhere in high-iron environments. Conversely, iron depletion promoted the differentiation of tachyzoites into bradyzoites. Proteomic analysis further revealed proteins affected by iron depletion and identified the involvement of phosphotyrosyl phosphatase activator proteins in bradyzoite formation.

Dietary knowledge-attitude-practice status in hemodialysis patients: a latent profile analysis.

BACKGROUND: Hemodialysis patients require a reasonable dietary intake to manage their disease progression effectively. However, there is limited research on these patients' overall dietary knowledge, attitude, and practice (KAP) status. This study aimed to investigate the dietary KAP status and latent profiles in hemodialysis patients and identify sociodemographic and disease-related factors associated with these profiles and dietary practice. METHODS: A multicenter cross-sectional study involving 425 hemodialysis patients was conducted. A dietary KAP questionnaire in hemodialysis patients was used to evaluate the dietary KAP of the patients. A structural equation model was employed to analyze the correlations between dietary knowledge, attitude, and practice. Multiple linear regression analysis was used to identify factors associated with dietary practice scores. Latent profile analysis was conducted to determine the latent profiles of dietary KAP, and binary logistic regression was used to explore the sociodemographic and disease-related characteristics associated with each KAP profile in hemodialysis patients. RESULTS: The normalized average scores for dietary knowledge, attitude, and practice in hemodialysis patients were 0.58, 0.82, and 0.58, respectively. The structural equation model revealed significant positive correlations between dietary knowledge and attitude, and attitude and practice. Attitude played an indirect effect between knowledge and practice. Gender, cerebrovascular disease, and dietary attitude scores were identified as independent influencing factors for dietary practice scores. Two dietary KAP profiles were developed: a profile with general knowledge and attitude but low practice (40.2%) and a profile with general knowledge and attitude and high practice (59.8%). Binary logistic regression analysis indicated gender and monthly income per household significantly predicted membership in each KAP profile. CONCLUSIONS: The dietary practice of hemodialysis patients requires improvement. It is necessary to develop more individualized dietary interventions for these patients. Further exploration is needed to understand the motivation of patients to change their dietary behavior.

Development and Metabolomic Profiles of Bactrocera dorsalis (Diptera: Tephritidae) Larvae Exposed to Phytosanitary Irradiation Dose in Hypoxic Environment Using DI-SPME-GC/MS.

X-ray irradiation and modified atmospheres (MAs) provide eco-friendly, chemical-free methods for pest management. Although a low-oxygen atmospheric treatment improves the performance of some irradiated insects, its influence on the irradiation of quarantine insects and its impacts on pest control efficacy have yet to be investigated. Based on bioassay results, this study employed direct immersion solid-phase microextraction (DI-SPME) combined with gas chromatography-mass spectrometry (GC-MS) to determine metabolic profiles of late third-instar B. dorsalis larvae under normoxia (CON, Air), hypoxia (95% N2 + 5% O2, HY), super-hypoxia (99.5% N2 + 0.5% O2, Sup-HY), irradiation-alone (116 Gy, IR-alone), hypoxia + irradiation (HY + IR) and super-hypoxia + irradiation (Sup-HY + IR). Our findings reveal that, compared to the IR-alone group, the IR treatment under HY and Sup-HY (HY + IR and Sup-HY + IR) increases the larval pupation of B. dorsalis, and weakens the delaying effect of IR on the larval developmental stage. However, these 3 groups further hinder adult emergence under the phytosanitary IR dose of 116 Gy. Moreover, all IR-treated groups, including IR-alone, HY + IR, and Sup-HY + IR, lead to insect death as a coarctate larvae or pupae. Pathway analysis identified changed metabolic pathways across treatment groups. Specifically, changes in lipid metabolism-related pathways were observed: 3 in HY vs. CON, 2 in Sup-HY vs. CON, and 5 each in IR-alone vs. CON, HY + IR vs. CON, and Sup-HY + IR vs. CON. The treatments of IR-alone, HY + IR, and Sup-HY + IR induce comparable modifications in metabolic pathways. However, in the HY + IR, and Sup-HY + IR groups, the third-instar larvae of B. dorsalis demonstrate significantly fewer changes. Our research suggests that a low-oxygen environment (HY and Sup-HY) might enhance the radiation tolerance in B. dorsalis larvae by stabilizing lipid metabolism pathways at biologically feasible levels. Additionally, our findings indicate that the current phytosanitary IR dose contributes to the effective management of B. dorsalis, without being influenced by radioprotective effects. These results hold significant importance for understanding the biological effects of radiation on B. dorsalis and for developing IR-specific regulatory guidelines under MA environments.

PI3Kα inhibitor GNE-493 triggers antitumor immunity in murine lung cancer by inducing immunogenic cell death and activating T cells.

Phosphatidylinositol 3-kinase (PI3K) is frequently hyperactivated in cancer, playing pivotal roles in the pathophysiology of both malignant and immune cells. The impact of PI3K inhibitors on the tumor microenvironment (TME) within lung cancer remains largely unknown. In this study, we explored the regulatory effects of GNE-493, an innovative dual inhibitor of PI3K and mammalian target of rapamycin (mTOR), on the TME of lung cancer. First, through the analysis of The Cancer Genome Atlas-lung squamous cell carcinoma (LUSC) cohort, we found PIK3CA to be related to CD8 T cells, which may affect the overall survival rate of patients by affecting CD8 function. We herein demonstrated that GNE-493 can significantly inhibit tumor cell proliferation and promote cell apoptosis while increasing the expression of the immunogenic death-related molecules CRT and HSP70 using in vitro cell proliferation and apoptosis experiments on the murine KP lung cancer cell line and human A549 lung cancer cell line. Next, through the establishment of an orthotopic tumor model in vivo, it was found that after GNE-493 intervention, the infiltration of CD4+ and CD8+ T cells in mouse lung tumor was significantly increased, and the expression of CRT in tumors could be induced to increase. To explore the mechanisms underlying PI3K inhibition-induced changes in the TME, the gene expression differences of T cells in the control group versus GNE-493-treated KP tumors were analyzed by RNA-seq, and the main effector pathway of anti-tumor immunity was identified. The IFN/TNF family molecules were significantly upregulated after GNE-493 treatment. In summary, our findings indicate that GNE-493 promotes immunogenic cell death in lung cancer cells, and elucidates its regulatory impact on molecules associated with the adaptive immune response. Our study provides novel insights into how PI3K/mTOR inhibitors exert their activity by modulating the tumor-immune interaction.

Spatially resolved single-cell atlas of ascidian endostyle provides insight into the origin of vertebrate pharyngeal organs.

The pharyngeal endoderm, an innovation of deuterostome ancestors, contributes to pharyngeal development by influencing the patterning and differentiation of pharyngeal structures in vertebrates; however, the evolutionary origin of the pharyngeal organs in vertebrates is largely unknown. The endostyle, a distinct pharyngeal organ exclusively present in basal chordates, represents a good model for understanding pharyngeal organ origins. Using Stereo-seq and single-cell RNA sequencing, we constructed aspatially resolved single-cell atlas for the endostyle of the ascidian Styela clava. We determined the cell composition of the hemolymphoid region, which illuminates a mixed ancestral structure for the blood and lymphoid system. In addition, we discovered a cluster of hair cell-like cells in zone 3, which has transcriptomic similarity with the hair cells of the vertebrate acoustico-lateralis system. These findings reshape our understanding of the pharynx of the basal chordate and provide insights into the evolutionary origin of multiplexed pharyngeal organs.

Photoredox-Catalyzed Alkene Amination: C(sp2)-H/N-H Radical-Radical Cross Dehydrogenative Coupling.

Direct alkene C-H/N-H cross dehydrogenative coupling is an infrequent, highly challenging transformation. Herein, a photoredox radical-radical cross-coupling reaction between ketene dithioacetal as a persistent alkene radical cation and azole nitrogen center radical (NCR) was developed. This direct alkene amination proceeded through a synergistic photoredox and cobalt catalysis, with only H2 evolution. The reaction showed excellent tolerance and highly regio- and stereospecific manner, expanding the scope of C(sp2)-N construction methods and radical cross-coupling modes.