Two new species of Paraphlomis (Lamiales, Lamiaceae) from limestone karsts in Guangdong Province, China.

Paraphlomisqingyuanensis and P.baiwanensis (Lamiaceae), two new species from the limestone area in Guangdong Province, China, are described. Morphologically, both species belong to P.ser.Subcoriaceae C.Y. Wu & H.W. Li. A close relationship between the two new and P.subcoriacea was revealed by molecular phylogenetic analyses based on ETS and ITS. Further morphological and population genetic evidence indicated that they are distinct species in Paraphlomis. According to the IUCN Red List Categories and Criteria, P.qingyuanensis and P.baiwanensis were assessed as Endangered (EN) and Deficient (DD), respectively.

Cytoplasmic Lipid Droplets Predict Worse Prognosis in Diffuse Large B-Cell Lymphoma: Next-Generation Sequencing Deciphering Lipogenic Genes.

Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy fluorescent stain, and electron microscopy. Second, in a cohort of DLBCL patients (n=52) we showed that LDs in effusional lymphoma cells were associated with a poorer prognosis (P=0.029, log-rank test) and higher International Prognostic Index (IPI) score (94% vs. 66%, P=0.026) than those without. Moreover, using adipophilin as a surrogate marker for LDs, we found in another cohort of biopsy specimen (n=85) that expression of adipophilin by lymphoma cells predicted a poorer prognosis (P=0.007, log-rank test) and higher IPI score (63% vs. 30%, P=0.005). In addition, whole exome sequencing of effusional DLBCL cells showed LD-positive DLBCL shared genetic features with the MCD (MYD88 and CD79B mutations) subtype and highlighted OSBPL10 and CUBN as the most frequently mutated genes involved in lipogenesis. Whole transcriptome analysis by comparing effusional DLBCL cells with versus without LDs showed upregulation of EHHADH, SLC1A1, CD96, INPP4B, and RNF183 relevant for lymphoma lipogenesis and upregulation of epithelial-mesenchymal transition and KRAS signaling pathways. Higher expression of EHHADH and CD96 were validated in LD-positive clinical samples and LD-rich cell lines than LD-poor cells along with the known lipogenic gene, FASN. Our findings highlight the roles of LDs and adipophilin expression in DLBCL, suggest that these markers may predict prognosis and show that lipogenic genes may be potential therapeutic targets.

Comparative study of the gut microbial community structure of Spodoptera frugiperda and Spodoptera literal (Lepidoptera).

Background: Spodoptera frugiperda, the fall armyworm is a destructive invasive pest, and S. litura the tobacco cutworm, is a native species closely related to S. frugiperda. The gut microbiota plays a vital role in insect growth, development, metabolism and immune system. Research on the competition between invasive species and closely related native species has focused on differences in the adaptability of insects to the environment. Little is known about gut symbiotic microbe composition and its role in influencing competitive differences between these two insects. Methods: We used a culture-independent approach targeting the 16S rRNA gene of gut bacteria of 5th instar larvae of S. frugiperda and S. litura. Larvae were reared continuously on maize leaves for five generations. We analyzed the composition, abundance, diversity, and metabolic function of gut microbiomes of S. frugiperda and S. litura larvae. Results: Firmicutes, Proteobacteria, and Bacteroidetes were the dominant bacterial phyla in both species. Enterococcus, ZOR0006, Escherichia, Bacteroides, and Lactobacillus were the genera with the highest abundance in S. frugiperda. Enterococcus, Erysipelatoclostridium, ZOR0006, Enterobacter, and Bacteroides had the highest abundance in S. litura. According to α-diversity analysis, the gut bacterial diversity of S. frugiperda was significantly higher than that of S. litura. KEGG analysis showed 15 significant differences in metabolic pathways between S. frugiperda and S. litura gut bacteria, including transcription, cell growth and death, excretory system and circulatory system pathways. Conclusion: In the same habitat, the larvae of S. frugiperda and S. litura showed significant differences in gut bacterial diversity and community composition. Regarding the composition and function of gut bacteria, the invasive species S. frugiperda may have a competitive advantage over S. litura. This study provides a foundation for developing control strategies for S. frugiperda and S. litura.

Association between Adverse Psychological Emotions and Postoperative Brace for Adolescent Idiopathic Scoliosis: A Prospective Cohort Study with Propensity Score Matching.

OBJECTIVE: Although the advantages of postoperative braces have been verified in many fields, it is not clear whether postoperative braces can help reduce patients' adverse psychological emotions such as kinesiophobia, anxiety, and depression. This study aims to analyze whether the use of a postoperative brace helps reduce adverse psychological emotions in adolescent idiopathic scoliosis (AIS) patients undergoing spinal deformity surgeries. METHODS: All consecutive patients who underwent spinal corrective surgeries at our institution between April 2023 and July 2023 formed the prospective cohort. Outcome measures were collected in the preoperative period, 3 months after surgery, and 6 months after surgery. All patients were assessed using the Tampa scale for kinesiophobia (TSK), the hospital anxiety and depression scale (HADS), and the numerical rating scale (NRS). A statistical model of propensity score matching was used to eliminate potential selection bias and maintain comparability. Multivariate linear regression models were used to determine the relationship between postoperative brace and adverse psychological emotions. RESULTS: After propensity score matching, this study ultimately enrolled 150 patients. There were no significant differences between the two groups in terms of demographic and perioperative variables. The fully adjusted model showed that the TSK scores of the non-brace group at the 3-month (ꞵ = 2.50, 95% CI 0.80-4.20, p = 0.005) and 6-month follow-up (ꞵ = 2.75, 95% CI 0.75-4.74, p = 0.007) were significantly higher than those of the brace group. The HADS score of the non-brace group at the 3-month follow-up was significantly higher than that of the brace group (ꞵ = 1.75, 95% CI 0.28-3.22, p = 0.019). The NRS score of the non-brace group at the 3-month follow-up was significantly higher than that of the brace group (ꞵ = 0.69, 95% CI 0.05-1.33, p = 0.034). At the 6-month follow-up, there were no significant difference for HADS score or NRS score between the two groups. CONCLUSION: In the early postoperative period, the postoperative brace could provide AIS patients with psychological supports and help them reduce the frequency of adverse psychological emotions. The postoperative brace could continuously improve the fear of movement within 6 months after surgery, and help reduce anxiety, depression, and pain within 3 months after surgery.

Identification of Novel Hb Guiyang [HBA2: c.151C > A α2 50 (CE8) His- Asn] and Phenotype- Genotype Correlation of Abnormal Hemoglobins in Guizhou, Southwest China.

Purpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China. Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and ß - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis. Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and ß globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes. Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin.

Epitope screening and self-assembled nanovaccine molecule design of PDCoV-S protein based on immunoinformatics.

Based on the whole virus or spike protein of pigs, δ coronavirus (PDCoV) as an immunogen may have unrelated antigenic epitope interference. Therefore, it is essential for screening and identifying advantageous protective antigen epitopes. In addition, immunoinformatic tools are described as an important aid in determining protective antigenic epitopes. In this study, the primary, secondary, and tertiary structures of vaccines were measured using ExPASy, PSIPRED 4.0, and trRosetta servers. Meanwhile, the molecular docking analysis and vector of the candidate nanovaccine were constructed. The immune response of the candidate vaccine was simulated and predicted using the C-ImmSim server. This experiment screened B cell epitopes with strong immunogenicity and high conservation, CTL epitopes, and Th epitopes with IFN-γ and IL-4 positive spike proteins. Ferritin is used as a self-assembled nanoparticle element for designing candidate nanovaccine. After analysis, it has been found to be soluble, stable, non-allergenic, and has a high affinity for its target receptor, TLR-3. The preliminary simulation analysis results show that the candidate nanovaccine has the ability to induce a humoral and cellular immune response. Therefore, it may provide a new theoretical basis for research on coronavirus self-assembled nanovaccines. It may be an effective candidate vaccine for controlling and preventing PDCoV.

Pore walls as high-way for efficient bulk charge transfer in porous SrTiO3 single crystals boosting photocatalytic overall water splitting.

Suppressing carrier recombination in bulk and facilitating carrier transfer to surface via rational structure design is of great significance to improve solar-to-H2 conversion efficiency. We demonstrate a facile hydrothermal method to synthesize porous SrTiO3 single crystals (SrTiO3-P) with exposed (001) facets by introducing carbon spheres as templates. The obviously increased surface photovoltage and photocurrent response indicate that the interconnected pore walls act as enormous charge transfer "highways", accelerating carrier transport from bulk to surface. Furthermore, the absence of grain boundaries and high crystallinity could also lower the carrier recombination rate. Thus, the SrTiO3-P photocatalyst loaded with Rh/Cr2O3 as cocatalyst exhibits 1.5 times higher overall water splitting activity than that of solid SrTiO3, with gas evolution rate of 19.99 µmol h-1 50 mg-1 for H2 and 11.37 µmol h-1 50 mg-1 for O2. Additionally, SrTiO3-P also shows superior stability without any decay during cycling testing. This work provides a new insight into designing efficient multicomponent photocatalysts with a single-crystal porous structure.

RNA-Seq Reveals That Multiple Pathways Are Involved in Tuber Expansion in Tiger Nuts (Cyperus esculentus L.).

The tiger nut (Cyperus esculentus L.) is a usable tuber and edible oil plant. The size of the tubers is a key trait that determines the yield and the mechanical harvesting of tiger nut tubers. However, little is known about the anatomical and molecular mechanisms of tuber expansion in tiger nut plants. This study conducted anatomical and comprehensive transcriptomics analyses of tiger nut tubers at the following days after sowing: 40 d (S1); 50 d (S2); 60 d (S3); 70 d (S4); 90 d (S5); and 110 d (S6). The results showed that, at the initiation stage of a tiger nut tuber (S1), the primary thickening meristem (PTM) surrounded the periphery of the stele and was initially responsible for the proliferation of parenchyma cells of the cortex (before S1) and then the stele (S2-S3). The increase in cell size of the parenchyma cells occurred mainly from S1 to S3 in the cortex and from S3 to S4 in the stele. A total of 12,472 differentially expressed genes (DEGs) were expressed to a greater extent in the S1-S3 phase than in S4-S6 phase. DEGs related to tuber expansion were involved in cell wall modification, vesicle transport, cell membrane components, cell division, the regulation of plant hormone levels, signal transduction, and metabolism. DEGs involved in the biosynthesis and the signaling of indole-3-acetic acid (IAA) and jasmonic acid (JA) were expressed highly in S1-S3. The endogenous changes in IAA and JAs during tuber development showed that the highest concentrations were found at S1 and S1-S3, respectively. In addition, several DEGs were related to brassinosteroid (BR) signaling and the G-protein, MAPK, and ubiquitin-proteasome pathways, suggesting that these signaling pathways have roles in the tuber expansion of tiger nut. Finally, we come to the conclusion that the cortex development preceding stele development in tiger nut tubers. The auxin signaling pathway promotes the division of cortical cells, while the jasmonic acid pathway, brassinosteroid signaling, G-protein pathway, MAPK pathway, and ubiquitin protein pathway regulate cell division and the expansion of the tuber cortex and stele. This finding will facilitate searches for genes that influence tuber expansion and the regulatory networks in developing tubers.

Nanoinjection: A Platform for Innovation in Ex Vivo Cell Engineering.

ConspectusIn human cells, intracellular access and therapeutic cargo transport, including gene-editing tools (e.g., CRISPR-Cas9 and transposons), nucleic acids (e.g., DNA, mRNA, and siRNA), peptides, and proteins (e.g., enzymes and antibodies), are tightly constrained to ensure healthy cell function and behavior. This principle is exemplified in the delivery mechanisms of chimeric antigen receptor (CAR)-T cells for ex-vivo immunotherapy. In particular, the clinical success of CAR-T cells has established a new standard of care by curing previously incurable blood cancers. The approach involves the delivery, typically via the use of electroporation (EP) and lentivirus, of therapeutic CAR genes into a patient's own T cells, which are then engineered to express CARs that target and combat their blood cancer. But the key difficulty lies in genetically manipulating these cells without causing irreversible damage or loss of function─all the while minimizing complexities of manufacturing, safety concerns, and costs, and ensuring the efficacy of the final CAR-T cell product.Nanoinjection─the process of intracellular delivery using nanoneedles (NNs)─is an emerging physical delivery route that efficiently negotiates the plasma membrane of many cell types, including primary human T cells. It occurs with minimal perturbation, invasiveness, and toxicity, with high efficiency and throughput at high spatial and temporal resolutions. Nanoinjection promises greatly improved delivery of a broad range of therapeutic cargos with little or no damage to those cargos. A nanoinjection platform allows these cargos to function in the intracellular space as desired. The adaptability of nanoinjection platforms is now bringing major advantages in immunomodulation, mechanotransduction, sampling of cell states (nanobiopsy), controlled intracellular interrogation, and the primary focus of this account─intracellular delivery and its applications in ex vivo cell engineering.Mechanical nanoinjection typically exerts direct mechanical force on the cell membrane, offering a straightforward route to improve membrane perturbation by the NNs and subsequent transport of genetic cargo into targeted cell type (adherent or suspension cells). By contrast, electroactive nanoinjection is controlled by coupling NNs with an electric field─a new route for activating electroporation (EP) at the nanoscale─allowing a dramatic reduction of the applied voltage to a cell and so minimizing post-EP damage to cells and cargo, and overcoming many of the limitations of conventional bulk EP. Nanoinjection transcends mere technique; it is an approach to cell engineering ex vivo, offering the potential to endow cells with new, powerful features such as generating chimeric antigen receptor (CAR)-T cells for future CAR-T cell technologies.We first discuss the manufacturing of NN devices (Section 2), then delve into nanoinjection-mediated cell engineering (Section 3), nanoinjection mechanisms and interfacing methodologies (Section 4), and emerging applications in using nanoinjection to create functional CAR-T cells (Section 5).

Spartina alterniflora invasion benefits blue carbon sequestration in China.

Spartina alterniflora has rapidly and extensively encroached on China's coastline over the past decades. Among the coastal areas invaded by S. alterniflora, at most 93% are mudflats. However, the effect of S. alterniflora invasion on soil organic carbon (SOC) stocks of coastal mudflats has not been systematically studied on a national scale. Here, we quantified the nationwide changes in SOC stocks in coastal mudflats associated with S. alterniflora invasion between 1990 and 2020. We found that S. alterniflora invasion significantly enhanced SOC stocks in coastal China. Nonetheless, the benefit of S. alterniflora invasion of coastal SOC stock may be weakened by continuing human intervention. We found that S. alterniflora invading mudflats added 2.3 Tg SOC stocks to China's coastal blue carbon, while 1.78 Tg SOC stocks were lost mainly due to human activities, resulted in a net SOC stock gain of 0.52 Tg C. These findings overturned the traditionally thought that S. alterniflora invasion would reduce ecosystem services by highlighting that the historical invasion of S. alterniflora has broadly and consistently enhanced blue carbon stock in coastal China.

Tumour organoids and assembloids: Patient-derived cancer avatars for immunotherapy.

BACKGROUND: Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch-to-batch variations, lack of the native microenvironment and clinical applicability. MAIN BODY: The concept of organoids has derived patient-derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, 'tumour assembloids' inspired by cell-coculture technology have attracted attention to complement the current PDTO technology. High-quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour-infiltrating lymphocyte, T cell receptor-engineered T cell and chimeric antigen receptor-T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. CONCLUSION: Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre-clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. KEY POINTS: The current PDTO models have not yet constructed key cellular and non-cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.

Discovery of a Long Half-Life AURKA Inhibitor to Treat MYC-Amplified Solid Tumors as a Monotherapy and in Combination with Everolimus.

Aurora kinase inhibitors, such as alisertib, can destabilize MYC-family oncoproteins and have demonstrated compelling antitumor efficacy. In this study, we report 6K465, a novel pyrimidine-based Aurora A inhibitor, that reduces levels of c-MYC and N-MYC oncoproteins more potently than alisertib. In an analysis of the antiproliferative effect of 6K465, the sensitivities of small cell lung cancer (SCLC) and breast cancer cell lines to 6K465 were strongly associated with the protein levels of c-MYC and/or N-MYC. We also report DBPR728, an acyl-based prodrug of 6K465 bearing fewer hydrogen-bond donors, that exhibited 10-fold improved oral bioavailability. DBPR728 induced durable tumor regression of c-MYC- and/or N-MYC-overexpressing xenografts including SCLC, triple-negative breast cancer, hepatocellular carcinoma, and medulloblastoma using a 5-on-2-off or once-a-week dosing regimen on a 21-day cycle. A single oral dose of DBPR728 at 300 mg/kg induced c-MYC reduction and cell apoptosis in the tumor xenografts for more than 7 days. The inhibitory effect of DBPR728 at a reduced dosing frequency was attributed to its uniquely high tumor/plasma ratio (3.6-fold within 7 days) and the long tumor half-life of active moiety 6K465. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC-driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC and/or N-MYC.

TIGIT Blockade Reshapes the Tumor Microenvironment Based on the Single-cell RNA-Sequencing Analysis.

SUMMARY: Immune checkpoint blockade therapy is a pivotal approach in treating malignant tumors. TIGIT has emerged as a focal point of interest among the diverse targets for tumor immunotherapy. Nonetheless, there is still a lack of comprehensive understanding regarding the immune microenvironment alterations following TIGIT blockade treatment. To bridge this knowledge gap, we performed single-cell sequencing on mice both before and after the administration of anti-TIGIT therapy. Our analysis revealed that TIGIT was predominantly expressed on T cells and natural killer (NK) cells. The blockade of TIGIT exhibited inhibitory effects on Treg cells by downregulating the expression of Foxp3 and reducing the secretion of immunosuppressive cytokines. In addition, TIGIT blockade facilitated the activation of NK cells, leading to an increase in cell numbers, and promoted cDC1 maturation through the secretion of XCL1 and Flt3L. This activation, in turn, stimulated the TCR signaling of CD8 + T cells, thereby enhancing their antitumor effect. Consequently, anti-TIGIT therapy demonstrated substantial potential for cancer immunotherapy. Our research provided novel insights into future therapeutic strategies targeting TIGIT for patients with cancer.

Screening and functional validation of the core detoxification genes conferring broad-spectrum response to insecticides in Spodoptera frugiperda.

BACKGROUND: Fall armyworm, Spodoptera frugiperda, a formidable agricultural pest, has developed resistance to various synthetic insecticides. However, how S. frugiperda utilizes its limited energy and resources to deal with various insecticides remains largely unexplored. RESULTS: We utilized transcriptome sequencing to decipher the broad-spectrum adaptation mechanism of S. frugiperda to eight insecticides with distinct modes-of-action. Analysis of the Venn diagram revealed that 1014 upregulated genes and 778 downregulated genes were present in S. frugiperda treated with at least five different insecticides, compared to the control group. Exposure to various insecticides led to the significant upregulation of eight cytochrome P450 monooxygenases (P450s), four UDP glucosyltransferases (UGTs), two glutathione-S-transferases (GSTs) and two ATP-binding cassette transporters (ABCs). Among them, the sfCYP340AD3 and sfCYP4G74 genes were demonstrated to respond to stress from six different insecticides in S. frugiperda, as evidenced by RNA interference and toxicity bioassays. Furthermore, homology modeling and molecular docking analyses showed that sfCYP340AD3 and sfCYP4G74 possess strong binding affinities to a variety of insecticides. CONCLUSION: Collectively, these findings showed that S. frugiperda utilizes a battery of core detoxification genes to cope with the exposure of synthetic insecticides. This study also sheds light on the identification of efficient insecticidal targets gene and the development of resistance management strategies in S. frugiperda, thereby facilitating the sustainable control of this serious pest. © 2024 Society of Chemical Industry.

Effective nitrogen doping of TiO2 polymorphs at mild temperatures for visible-light-responsive hydrogen evolution.

Herein, a mild-temperature nitrogen doping route with the urea-derived gaseous species as the active doping agent is proposed to realize visible-light-responsive photocatalytic hydrogen evolution both for the anatase and rutile TiO2. DFT simulations reveal that the cyanic acid (HOCN), derived from the decomposition of urea, plays a curial role in the effective doping of nitrogen in TiO2 at mild temperatures. Photocatalytic performance demonstrates that both the anatase and rutile TiO2 doped at mild temperatures exhibit the highest hydrogen evolution rates, although the ones prepared at high temperatures possess higher absorbance in the visible range. Steady-state and transient surface photovoltage characterizations of these doped TiO2 polymorphs prepared at different temperatures reveal that harsh conditions (high temperature reaction) typically result in the formation of intrinsic defects that are detrimental to the transport of the low-energy visible-light-induced electrons, while the mild-temperature nitrogen-doping could flatten the pristine upward band bending without triggering the formation of Ti3+, thus achieving enhanced visible-light-responsive hydrogen evolution rates. We anticipate that our findings will provide inspiring information for shrinking the gap between the visible-light-absorbance and the visible-light-responsiveness in the band engineering of wide-bandgap metal-oxide photocatalysts.

Using scanning electron microscopy and molecular data to discover a new species from old herbarium collections: The case of Phlomoideshenryi (Lamiaceae, Lamioideae).

Phlomoides is one of the largest genera of Lamiaceae with approximately 150-170 species distributed mainly in Eurasia. In this study, we describe and illustrate a new species, P.henryi, which was previously misidentified as P.bracteosa, from Yunnan Province, southwest China. Molecular phylogenetic analyses revealed that P.henryi is found within a clade in which most species lack basal leaves. In this clade, the new species is morphologically distinct from P.rotata in having an obvious stem and, from the rest, by having transparent to white trichomes inside the upper corolla lip. In addition, micro-features of trichomes on the calyx and leaf epidermis can differentiate the new species from other species grouped in the same clade and a key, based on trichome morphology for these species, is provided. The findings demonstrate that the use of scanning electron microscopy can reveal inconspicuous morphological affinities amongst morphologically similar species and play an important role in the taxonomic study of the genus Phlomoides.

Elevated INHBA Promotes Tumor Progression of Cervical Cancer.

Objectives: This study aimed to explore the role of inhibin subunit beta A (INHBA) in the progression of cervical cancer (CCa) and investigate its potential as a therapeutic target. Specifically, the objectives were to assess the expression levels of INHBA in CCa, examine its correlation with patient survival, and elucidate its impact on CCa cell proliferation, cell cycle regulation, migration, invasion, and in vivo tumor growth and metastasis. Methods: To achieve the objectives, we conducted a comprehensive set of experimental methods. INHBA expression in CCa was analyzed, and its association with patient survival was assessed using clinical data. In vitro experiments involved the investigation of INHBA's effects on CCa cell proliferation, cell cycle dynamics, migration, and invasion through the epithelial-mesenchymal transition (EMT) process. Additionally, in vivo experiments were performed to evaluate the influence of INHBA on CCa growth and lung metastasis. Results: The results of this study revealed upregulated expression of INHBA in CCa, with a significant association between high INHBA expression and poor patient survival. Functionally, INHBA was found to promote the proliferation of CCa cells, regulate the cell cycle, and enhance migration and invasion through the EMT process in vitro. Moreover, in vivo experiments demonstrated that INHBA facilitated the growth and lung metastasis of CCa. Conclusion: In conclusion, our findings suggest that INHBA plays a crucial role in the progression of cervical cancer. The upregulation of INHBA is associated with poor patient survival, and its involvement in promoting key aspects of cancer progression makes it a potential therapeutic target for CCa treatment. These results provide valuable insights into the molecular mechanisms underlying CCa and offer a foundation for further exploration of targeted therapeutic interventions.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.