Machine learning-based autophagy-related prognostic signature for personalized risk stratification and therapeutic approaches in bladder cancer.

OBJECTIVE: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited. METHODS: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene. RESULTS: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa. CONCLUSIONS: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients.

[Mechanism of salidroside in inhibiting proliferation, migration and promoting phenotypic switching of arterial smooth muscle cells].

This study aims to examine the effect of salidroside(SAL) on the phenotypic switching of human aortic smooth muscle cells(HASMC) induced by the platelet-derived growth factor-BB(PDGF-BB) and investigate the pharmacological mechanism. Firstly, the safe concentration of SAL was screened by the lactate dehydrogenase release assay. HASMC were divided into control, model, and SAL groups, and the cells in other groups except the control group were treated with PDGF-BB for the modeling of phenotypic switching. Cell proliferation and migration were detected by the cell-counting kit(CCK-8) assay and Transwell assay, respectively. The cytoskeletal structure was observed by F-actin staining with fluorescently labeled phalloidine. The protein levels of proliferating cell nuclear antigen(PCNA), migration-related protein matrix metalloprotein 9(MMP-9), fibronectin, α-smooth muscle actin(α-SMA), and osteopontin(OPN) were determined by Western blot. To further investigate the pharmacological mechanism of SAL, this study determined the expression of protein kinase B(Akt) and mammalian target of rapamycin(mTOR), as well as the upstream proteins phosphatase and tensin homologue(PTEN) and platelet-derived growth factor receptor ß(PDGFR-ß) and the downstream protein hypoxia-inducible factor-1α(HIF-1α) of the Akt/mTOR signaling pathway. The results showed that the HASMCs in the model group presented significantly increased proliferation and migration, the switching from a contractile phenotype to a secretory phenotype, and cytoskeletal disarrangement. Compared with the model group, SAL weakened the proliferation and migration of HASMC, promoted the expression of α-SMA(a contractile phenotype marker), inhibited the expression of OPN(a secretory phenotype marker), and repaired the cytoskeletal disarrangement. Furthermore, compared with the control group, the modeling up-regulated the levels of phosphorylated Akt and mTOR and the relative expression of PTEN, HIF-1α, and PDGFR-ß. Compared with the model group, SAL down-regulated the protein levels of phosphorylated Akt and mTOR, PTEN, PDGFR-ß, and HIF-1α. In conclusion, SAL exerts a protective effect on the HASMCs exposed to PDGF-BB by regulating the PDGFR-ß/Akt/mTOR/HIF-1α signaling pathway.

Environmental explanation of prostate cancer progression based on the comprehensive analysis of polychlorinated biphenyls.

OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa). METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells. RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 µM showed increased proliferation and invasion capabilities. CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.

Wogonin protects against bleomycin-induced mouse pulmonary fibrosis via the inhibition of CDK9/p53-mediated cell senescence.

Pulmonary fibrosis (PF) is a fatal interstitial lung disease associated with declining pulmonary function but currently with few effective drugs. Cellular senescence has been implicated in the pathogenesis of PF and could be a potential therapeutic target. Emerging evidence suggests wogonin, the bioactive compound isolated from Scutellaria baicalensis, owns the anti-senescence properties, however, the possible impact of wogonin on PF and the potential mechanisms remain unclear. In this study, a well-established mouse model of PF was utilized which mice were administrated with bleomycin (BLM). Strikingly, wogonin treatment significantly reduced fibrosis deposition in the lung induced by BLM. In vitro, wogonin also suppressed fibrotic markers of cultured epithelial cells stimulated by BLM or hydrogen peroxide. Mechanistic investigation revealed that wogonin attenuated the expressions of DNA damage marker γ-H2AX and senescence-related markers including phosphorylated p53, p21, retinoblastoma protein (pRB), and senescence-associated ß-galactosidase (SA-ß-gal). Moreover, wogonin, as a direct and selective inhibitor of cyclin-dependent kinase 9 (CDK9), exhibited anti-fibrotic capacity by inhibiting CDK9 and p53/p21 signalling. In conclusion, wogonin protects against BLM-induced PF in mice through the inhibition of cell senescence via the regulation of CDK9/p53 and DNA damage pathway. This is the first study to demonstrate the beneficial effect of wogonin on PF, and its implication as a novel candidate for PF therapy.

Preservation of Pulp Vitality in Type IIIA Dens Invaginatus with an Extensive Peri-invagination Lesion: a case Report with 5-year Follow-up.

Dens invaginatus may be associated with peri-invagination lesions and vital pulp concurrently. This case report examines the successful preservation of vital pulp and minimally invasive treatment of invagination for Oehlers type IIIA dens invaginatus with an extensive peri-invagination lesion. A healthy 19-year-old man presented with occasional swelling of the left maxillary anterior region. Pulp vitality tests revealed vital and healthy tooth pulp. CBCT indicated Oehlers type IIIA dens invaginatus with an invagination parallel to the pulp cavity. The diagnosis was type IIIA dens invaginatus with a peri-invagination lesion. The treatment plans involved preservation of the vital pulp and minimally invasive treatment of the invagination. A 5-year follow-up revealed that both healing of the peri-invagination lesion and preservation of the vital pulp had been successful. Pulp vitality can be preserved in type IIIA dens invaginatus associated with a peri-invagination lesion through minimally invasive treatment of the invagination.

Magnetic resonance imaging-based radiomics nomogram for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer.

PURPOSE: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa). METHODS: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. RESULTS: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. CONCLUSION: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa.

Disturbance history, neighborhood crowding and soil conditions jointly shape tree growth in temperate forests.

Understanding how different mechanisms act and interact in shaping communities and ecosystems is essential to better predict their future with global change. Disturbance legacy, abiotic conditions, and biotic interactions can simultaneously influence tree growth, but it remains unclear what are their relative contributions and whether they have additive or interactive effects. We examined the separate and joint effects of disturbance intensity, soil conditions, and neighborhood crowding on tree growth in 10 temperate forests in northeast China. We found that disturbance was the strongest driver of tree growth, followed by neighbors and soil. Specifically, trees grew slower with decreasing initial disturbance intensity, but with increasing neighborhood crowding, soil pH and soil total phosphorus. Interestingly, the decrease in tree growth with increasing soil pH and soil phosphorus was steeper with high initial disturbance intensity. Testing the role of species traits, we showed that fast-growing species exhibited greater maximum tree size, but lower wood density and specific leaf area. Species with lower wood density grew faster with increasing initial disturbance intensity, while species with higher specific leaf area suffered less from neighbors in areas with high initial disturbance intensity. Our study suggests that accounting for both individual and interactive effects of multiple drivers is crucial to better predict forest dynamics.

Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

OBJECTIVE: To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway. METHODS: Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) in mice. RESULTS: Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P<0.01). Moreover, Scorpiones, Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase (p70S6K) (P<0.05 or P<0.01). In addition, they also decreased the expression of CD31, MVD, bFGF, TGF-ß1 and VEGF compared with the model group (P<0.05 or P<0.01). CONCLUSION: Scorpiones, Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1α signaling pathway.

In Vitro Propagation Technology for the Endangered Aquatic Species Nymphoides coronata.

Nymphoides coronata is an endangered aquatic plant species with significant medicinal and ecological importance. To preserve N. coronata from going extinct, we need to provide seedlings and efficient multiplication techniques so that it can be extensively studied. This study aimed to identify the most suitable sterilization treatment, growth medium, and substrate for the cultivation and propagation of N. coronata. Ethanol sterilization, fungicide treatment, and sterile water washing were the most important sterilization steps. A combination of 6-benzylaminopurine (6-BA) and indoleacetic acid (IAA) was the most suitable medium for bud induction and shoot proliferation. The use of α-naphthaleneacetic acid (NAA) increased the rooting rate and rooting time compared to indole-3-butyric acid (IBA). Increasing the concentration of NAA from 0.5 to 1.0 mg/L increased the rooting rate from 78 to 100% and reduced the rooting time from 7 to 5 days. The survival rate of N. coronata seedlings was 100% in a mixture of red soil and sand (1:1, w/w). As a result, the procedure mentioned above could potentially be used to safely propagate this rare species on a large scale. These findings provide valuable insights into the optimal conditions for the successful cultivation and propagation of N. coronata, which can contribute to the conservation and sustainable use of this important rare plant species.

Expert consensus on endodontic therapy for patients with systemic conditions.

The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Costunolide ameliorates MNNG-induced chronic atrophic gastritis through inhibiting oxidative stress and DNA damage via activation of Nrf2.

BACKGROUND: Chronic atrophic gastritis (CAG) is a chronic digestive disease. Modern research has revealed substantial evidence indicating that the progression of CAG is closely linked to the occurrence of oxidative stress-induced DNA damage and apoptosis in the gastric mucosa. Additionally, research has indicated that Costunolide (COS), the primary active compound found in Aucklandiae Radix, a traditional herb, exhibits antioxidant properties. Nevertheless, the therapeutic potential of COS in treating CAG and its molecular targets have not yet been determined. PURPOSE: The objective of this research was to explore the potential gastric mucosal protective effects and mechanisms of COS against N-Methyl-N´-nitro-N-nitrosoguanidine (MNNG)-induced CAG. METHODS: Firstly, the MNNG-induced rat CAG model was established in vivo. Occurrence of CAG was detected through macroscopic examination of the stomachs and H&E staining. Additionally, we assessed oxidative stress, DNA damage, and apoptosis using biochemical detection, Western blot, immunohistochemistry and immunofluorescence. Then, an in vitro model was developed to induce MNNG-induced damage in GES-1 cells, and the occurrence of cell damage was determined by Hoechst 33,342 staining and flow cytometry. Finally, the key targets of COS for the treatment of CAG were identified through molecular docking, cellular thermal shift assay (CETSA), and inhibitor ML385. RESULTS: In vivo studies demonstrated that COS promotes the expression of Nrf2 in gastric tissues. This led to an increased expression of SOD, GSH, HO-1, while reducing the production of MDA. Furthermore, COS inhibited DNA damage and apoptosis by suppressing the expression of γH2AX and PARP1 in gastric tissues. In vitro studies showed that COS effectively reversed apoptosis induced by MNNG in GES-1 cells. Additionally, COS interacted with Nrf2 to promote its expression. Furthermore, the expression levels of SOD, GSH, and HO-1 were augmented, while the generation of ROS and MDA was diminished. CONCLUSIONS: Our results indicate that COS exhibits therapeutic effects on CAG through the promotion of Nrf2 expression and inhibition of oxidative stress and DNA damage. Therefore, COS has the potential to provide new drugs for the treatment of CAG.

Pt1.8Pd0.2CuGa Intermetallic Nanocatalysts with Enhanced Methanol Oxidation Performance for Efficient Hybrid Seawater Electrolysis.

Seawater electrolysis is a potentially cost-effective approach to green hydrogen production, but it currently faces substantial challenges for its high energy consumption and the interference of chlorine evolution reaction (ClER). Replacing the energy-demanding oxygen evolution reaction with methanol oxidation reaction (MOR) represents a promising alternative, as MOR occurs at a significantly low anodic potential, which cannot only reduce the voltage needed for electrolysis but also completely circumvents ClER. To this end, developing high-performance MOR catalysts is a key. Herein, a novel quaternary Pt1.8Pd0.2CuGa/C intermetallic nanoparticle (i-NP) catalyst is reported, which shows a high mass activity (11.13 A mgPGM -1), a large specific activity (18.13 mA cmPGM -2), and outstanding stability toward alkaline MOR. Advanced characterization and density functional theory calculations reveal that the introduction of atomically distributed Pd in Pt2CuGa intermetallic markedly promotes the oxidation of key reaction intermediates by enriching electron concentration around Pt sites, resulting in weak adsorption of carbon-containing intermediates and favorable adsorption of synergistic OH- groups near Pd sites. MOR-assisted seawater electrolysis is demonstrated, which continuously operates under 1.23 V for 240 h in simulated seawater and 120 h in natural seawater without notable degradation.

Up-regulated ORC1 promotes lung adenocarcinoma by inhibiting ferroptosis via SLC7A11 dependent pathway.

Background: Lung adenocarcinoma (LUAD) is a pulmonary malignant disease that poses a high risk of mortality and morbidity. Previous study indicated that ORC1 plays an oncogenic function. However, the precise regulatory function that ORC1 serves in the progression of LUAD is still not clearly known. Methods: Bioinformatics analyses were performed using TCGA and GEO datasets. The human LUAD cell line NCIH1355, NCIH1568 as well as BEAS-2B cell line (human normal lung epithelial cell) were utilized for in vitro study. LUAD cell proliferation were determined via CCK-8 assays and RT-qPCR for ki-67. The relation of ORC1 and SLC7A11 was detected by Western blot and qPCR with or without sh-RNA. The expression level ACSL4, the biomarker of ferroptosis, were detected using RT-qPCR. Results: ORC1 and SLC7A11 exhibit high expression levels in both LUAD patients and cell lines, and are strongly associated with poor prognosis. In vitro experiments demonstrate that ORC1 and SLC7A11 promote proliferation of LUAD cell lines while inhibiting gefitinib-induced ferroptosis. Additionally, the function of ORC1 in LUAD cells is dependent on SLC7A11. Conclusion: ORC1 promotes LUAD cell proliferation and inhibits ferroptosis in a SLC7A11-dependent manner. This implies that ORC1 could potentially serve as a useful diagnosis biomarker and treatment target.

Effects of strengthening prospective nursing practice on sleep quality, anxiety, and depression of awake patients in intensive care unit.

BACKGROUND: The intensive care unit (ICU) is a specialized hospital department. Awake patients in the ICU frequently encounter adverse psychological states, such as anxiety and fear, often accompanied by poor sleep quality. This situation has garnered significant attention within the medical community. AIM: To investigate the impact of prospective nursing intervention strategies on the sleep quality and negative emotional state of conscious ICU patients. METHODS: One hundred and twenty ICU awake patients admitted to our hospital were selected and randomly divided into control (n = 60) and observation (n = 60) groups. Patients in the control group were cared for using the conventional nursing model, while patients in the observation group were cared for using the prospective nursing model. Sleep improvement was assessed using the International Standardized Sleep Efficiency Formula and Pittsburgh Sleep Quality Index (PSQI). The PSQI, Generalized Anxiety Disorder 7-item (GAD-7) scale, Self-Depression Scale (SDS), and satisfaction before and after treatment were used to assess the negative emotional states of patients under the two care models. RESULTS: Patient satisfaction in the observation group was significantly higher than in the control group. The GAD-7 and SDS scores in the observation group were significantly lower than those in the control group, and the total effective rate of sleep improvement in the observation group was significantly higher than in the control group. After treatment, the PSQI scores of the two groups significantly decreased (P < 0.05). The decrease in the observation group was more significant than that in the control group, and the difference between the two groups was statistically significant. CONCLUSION: Prospective nursing interventions can improve sleep quality and psychological levels and significantly affect conscious patients in the ICU, which is worthy of clinical application.

Blasting profile evaluation of sand-mud interbedded surrounding rock during the large-span tunnel construction.

The sand-mud interbedded surrounding rock contains discontinuities, such as horizontal bedding, joints, weak planes and weak interlayers. Drilling and blasting construction in this kind of surrounding rock is very likely to cause very serious over-/under-excavation phenomenon and excessive damage to surrounding rock, and the contour flatness after smooth blasting of the tunnel is also difficult to be guaranteed, which increases subsequent construction procedures and reduces production efficiency. In order to effectively evaluate the smooth blasting effect of the sand-mud interbedded surrounding rock tunnel, taking a tunnel project in southwest China as the research background, the blasting numerical simulation of the sand-mud interbedded surrounding rock tunnel was carried out using the dynamic analysis program, and the corresponding blasting optimization scheme was obtained. Subsequently, based on fuzzy mathematical theory, the evaluation system of blasting effect of sand-mud interbedded tunnel was established by combining the evaluation criteria of tunnel smooth blasting quality. Immediately afterwards, the weights of each influencing factor index were determined, and the blasting shaping effect of the original blasting scheme and the optimized blasting scheme was evaluated. Finally, the results have shown that the optimized tunnel blasting profile effect was better than the original blasting scheme. The corresponding research results have certain guiding significance for similar tunnel blasting effect evaluation and blasting parameter design.

Prognostic Value of Postoperative Complication for Gastric Cancer.

Background: The incidence of complications in gastric cancer (GC) patients after surgery was increasing, and it was not clear whether postoperative complications would have an impact on prognosis. The current study attempted to investigate the role of postoperative complication for prognosis on GC patients undergoing radical resection. Materials and Methods: Eligible studies were searched in three databases, including PubMed, Embase, and the Cochrane Library, in accordance with the searching strategy on September 4th, 2022. The survival values were most concerned; then, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled up. All prognostic values, including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and recurrence-free survival (RFS), were allowed. Subgroup analysis based on complication types was used for further in-depth research. Results: A total of 29 studies involving 33,858 patients were included in this study. Intra-abdominal abscess (19.4%) was the most common complications in the included studies, followed by anastomotic leakage (17.0%) and pneumonia (16.4%). There were 23, 4, 6, and 10 studies that reported OS, DFS, DSS, and RFS, respectively. After analysis, postoperative complication was found to be an independent prognostic factor for OS (HR = 1.52, I2 = 1.14%, 95% CI = 1.42-1.61, P = .00), DFS (HR = 1.71, I2 = 0.00%,95% CI = 1.44-1.98, P < .05), DSS (HR = 1.60, I2 = 54.58%, 95% CI = 1.26-1.93, P < .1), and RFS (HR = 1.26, I2 = 0.00%, 95% CI = 1.11-1.41, P < .05). Subgroup analysis found that noninfectious complication was not significantly associated with OS (HR = 1.39, I2 = 0.00%, 95% CI = 0.96-1.82, P > .05). Conclusion: Surgeons needed to pay more attention to GC patients who developed postoperative complications, especially infectious complications, and take proactive management to improve the prognosis.

Influence of Two Hexose Transporters on Substrate Affinity and Pathogenicity in Magnaporthe oryzae.

Hexose transporters (HXT) play a crucial role in the pathogenicity of Magnaporthe oryzae, serving not only as key facilitators for acquiring and transporting sugar nutrients to support pathogen development, but also as sugar sensors which receive transduction signals. The objective of this study is to investigate the impact of MoHXT1-3 on rice pathogenicity and hexose affinity. MoHXT1-3 deletion mutants were generated using CRISPR/Cas9 technology, and their affinity for hexose was evaluated through yeast complementation assays and electrophysiological experiments in Xenopus oocytes. The results suggest that MoHXT1 does not contribute to melanin formation or hexose transportation processes. Conversely, MoHXT2, despite displaying lower affinity towards the hexoses tested in comparison to MoHXT3, is likely to have a more substantial impact on pathogenicity. The analysis of the transcription profiles demonstrated that the deletion of MoHXT2 caused a decrease in the expression of MoHXT3, whereas the knockout of MoHXT3 resulted in an upregulation of MoHXT2 transcription. It is noteworthy that the MoHXT2M145K variant displayed an incapacity to transport hexoses. This investigation into the functional differences in hexose transporters in Magnaporthe oryzae provides insights into potential advances in new strategies to target hexose transporters to combat rice blast by blocking carbon nutrient supply.

Tumor microenvironment-responsive size-changeable and biodegradable HA-CuS/MnO2 nanosheets for MR imaging and synergistic chemodynamic therapy/phototherapy.

Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn2+, thereby enhancing the therapeutic efficiency. Furthermore, the T1-weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.