Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation.

Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A.

Efficient Photodegradation of Antibiotics by g-C3N4 and 3D flower-like Bi2WO6 Perovskite Structure: Insights into the Preparation, Evaluation, and Potential Mechanism.

Antibiotics are emerging organic pollutants that have attracted huge attention owing to their abundant use and associated ecological threats. The aim of this study is to develop and use photocatalysts to degrade antibiotics, including tetracycline (TC), ciprofloxacin (CIP), and amoxicillin (AMOX). Therefore, a novel Z-scheme heterojunction composite of g-C3N4 (gCN) and 3D flower-like Bi2WO6 (BW) perovskite structure was designed and developed, namely Bi2WO6/g-C3N4 (BW/gCN), which can degrade low-concentration of antibiotics in aquatic environments under visible light. According to the Density Functional Theory (DFT) calculation and the characterization results of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FITR), Scanning electron microscopy - energy spectroscopy (SEM-EDS) and X-ray photoelectron spectroscopy (XPS), this heterojunction was formed in the recombination process. Furthermore, the results of 15wt%-BW/gCN photocatalytic experiments showed that the photodegradation rates (Rp) of TC, CIP, and AMOX were 92.4%, 90.1% and 82.3%, respectively, with good stability in three-cycle photocatalytic experiments. Finally, the quenching experiment of free radicals showed that the holes (h+) and superoxide radicals (·O2-) play a more important role than the hydroxyl radicals (·OH) in photocatalysis. In addition, a possible antibiotic degradation pathway was hypothesized on the basis of High performance liquid chromatography (HPLC) analysis. In general, we have developed an effective catalyst for photocatalytic degradation of antibiotic pollutants and analyzed its photocatalytic degradation mechanism, which provides new ideas for follow-up research and expands its application in the field of antibiotic composite pollution prevention and control.

Pathway to Approval of Innovative Radiopharmaceuticals in China.

Since the late 1950s, radiopharmaceuticals have been used for diagnosis and treatment in clinical nuclear medicine in China. Over the decades, China has successfully established a relatively sophisticated system for radiopharmaceutical production and management, supported by state-of-the-art facilities. With the rapid growth of the national economy, the radiopharmaceutical market in China is expanding at a remarkable pace. This burgeoning market has led to an escalating demand for clinical-stage radiopharmaceuticals, either produced domestically or imported. Despite this positive trajectory, the development and application of radiopharmaceuticals in China have been hindered by several challenges that persist, such as inadequate research, insufficient investment, limited availability of radionuclides, shortage of trained personnel in related fields, and imperfections in policies and regulations. In an exciting development, the regulation reforms implemented since 2015 have positively affected China's drug regulatory system. The introduction of the "Mid- and Long-Term Development Plan (2021-2035) for Medical Isotopes" created concurrently an opportune environment for the advancement of innovative radiopharmaceuticals. In this review, we aim to provide an overview of the approval process for novel radiopharmaceuticals by the National Medical Products Administration and the status of radiopharmaceuticals in research and development in China. Preclinical development and clinical translation of radiopharmaceuticals are undergoing rapid evolution in China. As practitioners in the field in China, we provide several practical suggestions to stimulate open discussions and thoughtful consideration.

Revealing Hydrogen Bond Effect in Rechargeable Aqueous Zinc-Organic Batteries.

The surrounding hydrogen bond (H-bond) interaction around the active sites plays indispensable functions in enabling the organic electrode materials (OEMs) to fulfill their roles as ion reservoirs in aqueous zinc-organic batteries (ZOBs). Despite important, there are still no works could fully shed its real effects light on. Herein, quinone-based small molecules with a H-bond evolution model has been rationally selected to disclose the regulation and equilibration of H-bond interaction between OEMs, and OEM and the electrolyte. It has been found that only a suitable H-bond interaction could make the OEMs fully liberate their potential performance. Accordingly, the 2,5-diaminocyclohexa-2,5-diene-1,4-dione (DABQ) with elaborately designed H-bond structure exhibits a capacity of 193.3 mA h g-1 at a record-high mass loading of 66.2 mg cm-2 and 100% capacity retention after 1500 cycles at 5 A g-1. In addition, the DABQ//Zn battery also possesses air-rechargeable ability by utilizing the chemistry redox of proton. Our results put forward a specific pathway to precise utilization of H-bond to liberate the performance of OEMs.

Biomimetic-Mineralization-Assisted Self-Activation Creates a Delicate Porous Structure in Carbon Material for High-Rate Sodium Storage.

Porous carbons have shown their potential in sodium-ion batteries (SIBs), but the undesirable initial Coulombic efficiency (ICE) and rate capability hinder their practical application. Herein, learning from nature, we report an efficient method for fabricating a carbon framework (CK) with delicate porous structural regulation by biomimetic mineralization-assisted self-activation. The abundant pores and defects of the CK anode can improve the ICE and rate performance of SIBs in ether-based electrolytes, whereas they are confined in carbonate ester-based electrolytes. Notably, ether-based electrolytes enable CK anode to possess excellent ICE (82.9%) and high-rate capability (111.2 mAh g-1 at 50 A g-1). Even after 5500 cycles at a large current density of 10 A g-1, the capacity retention can still be maintained at 73.1%. More importantly, the full cell consisting of the CK anode and Na3V2(PO4)3 cathode delivers a high energy density of 204.4 Wh kg-1, with a power density of 2828.2 W kg-1. Such outstanding performance of the CK anode is attributed to (1) hierarchical pores, oxygen doping, and defects that pave the way for the transportation and storage of Na+, further enhancing ICE; (2) a high-proportion NaF-based solid-electrolyte-interphase (SEI) layer that facilitates Na+ storage kinetics in ether-based electrolytes; and (3) ether-based electrolytes that determine Na+ storage kinetics further to dominate the performance of SIBs. These results provide compelling evidence for the promising potential of our synthetic strategy in the development of carbon-based materials and ether-based electrolytes for electrochemical energy storage.

Prediction of prostate cancer aggressiveness using magnetic resonance imaging radiomics: a dual-center study.

PURPOSE: The Gleason score (GS) and positive needles are crucial aggressive indicators of prostate cancer (PCa). This study aimed to investigate the usefulness of magnetic resonance imaging (MRI) radiomics models in predicting GS and positive needles of systematic biopsy in PCa. MATERIAL AND METHODS: A total of 218 patients with pathologically proven PCa were retrospectively recruited from 2 centers. Small-field-of-view high-resolution T2-weighted imaging and post-contrast delayed sequences were selected to extract radiomics features. Then, analysis of variance and recursive feature elimination were applied to remove redundant features. Radiomics models for predicting GS and positive needles were constructed based on MRI and various classifiers, including support vector machine, linear discriminant analysis, logistic regression (LR), and LR using the least absolute shrinkage and selection operator. The models were evaluated with the area under the curve (AUC) of the receiver-operating characteristic. RESULTS: The 11 features were chosen as the primary feature subset for the GS prediction, whereas the 5 features were chosen for positive needle prediction. LR was chosen as classifier to construct the radiomics models. For GS prediction, the AUC of the radiomics models was 0.811, 0.814, and 0.717 in the training, internal validation, and external validation sets, respectively. For positive needle prediction, the AUC was 0.806, 0.811, and 0.791 in the training, internal validation, and external validation sets, respectively. CONCLUSIONS: MRI radiomics models are suitable for predicting GS and positive needles of systematic biopsy in PCa. The models can be used to identify aggressive PCa using a noninvasive, repeatable, and accurate diagnostic method.

Super-Assembled Multilayered Mesoporous TiO2 Nanorockets for Light-Powered Space-Confined Microfluidic Catalysis.

In the field of sustainable chemistry, it is still a significant challenge to realize efficient light-powered space-confined catalysis and propulsion due to the limited solar absorption efficiency and the low mass and heat transfer efficiency. Here, novel semiconductor TiO2 nanorockets with asymmetric, hollow, mesoporous, and double-layer structures are successfully constructed through a facile interfacial superassembly strategy. The high concentration of defects and unique topological features improve light scattering and reduce the distance for charge migration and directed charge separation, resulting in enhanced light harvesting in the confined nanospace and resulting in enhanced catalysis and self-propulsion. The movement velocity of double-layered nanorockets can reach up to 10.5 µm s-1 under visible light, which is approximately 57 and 119% higher than that of asymmetric single-layered TiO2 and isotropic hollow TiO2 nanospheres, respectively. In addition, the double-layered nanorockets improve the degradation rate of the common pollutant methylene blue under sustainable visible light with a 247% rise of first-order rate constant compared to isotropic hollow TiO2 nanospheres. Furthermore, FEA simulations reveal and confirm the double-layered confined-space enhanced catalysis and self-propulsion mechanism.

A Rotating Cathode with Periodical Changes in Electrolyte Layer Thickness for High-Rate Li‒O2 Batteries.

Li-O2 batteries (LOBs) possess the highest theoretical gravimetric energy density among all types of secondary batteries, but they are still far from practical applications. The poor rate performance resulting from the slow mass transfer is one of the primary obstacles in LOBs. To solve this issue, a rotating cathode with periodic changes in the electrolyte layer thickness is designed, decoupling the maximum transfer rate of Li+ and O2. During rotation, the thinner electrolyte layer on the cathode facilitates the O2 transfer, and the thicker electrolyte layer enhances the Li+ transfer. As a result, the rotating cathode enables the LOBs to undergo 58 cycles at 2.5 mA cm-2 and discharge stably even at a high current density of 7.5 mA cm-2. Besides, it also makes the batteries exhibit a large discharge capacity of 6.8 mAh cm-2, and the capacity decay is much slower with increasing current density. Notably, this rotating electrode holds great promise for utilization in other electrochemical cells involving gas-liquid-solid triple-phase interfaces, suggesting a viable approach to enhance the mass transfer in such systems.

Preclinical development of novel PD-L1 tracers and first-in-human study of [68Ga]Ga-NOTA-RW102 in patients with lung cancers.

BACKGROUND: The programmed cell death protein-1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis critically facilitates cancer cells' immune evasion. Antibody therapeutics targeting the PD-1/PD-L1 axis have shown remarkable efficacy in various tumors. Immuno-positron emission tomography (ImmunoPET) imaging of PD-L1 expression may help reshape solid tumors' immunotherapy landscape. METHODS: By immunizing an alpaca with recombinant human PD-L1, three clones of the variable domain of the heavy chain of heavy-chain only antibody (VHH) were screened, and RW102 with high binding affinity was selected for further studies. ABDRW102, a VHH derivative, was further engineered by fusing RW102 with the albumin binder ABD035. Based on the two targeting vectors, four PD-L1-specific tracers ([68Ga]Ga-NOTA-RW102, [68Ga]Ga-NOTA-ABDRW102, [64Cu]Cu-NOTA-ABDRW102, and [89Zr]Zr-DFO-ABDRW102) with different circulation times were developed. The diagnostic efficacies were thoroughly evaluated in preclinical solid tumor models, followed by a first-in-human translational investigation of [68Ga]Ga-NOTA-RW102 in patients with non-small cell lung cancer (NSCLC). RESULTS: While RW102 has a high binding affinity to PD-L1 with an excellent KD value of 15.29 pM, ABDRW102 simultaneously binds to human PD-L1 and human serum albumin with an excellent KD value of 3.71 pM and 3.38 pM, respectively. Radiotracers derived from RW102 and ABDRW102 have different in vivo circulation times. In preclinical studies, [68Ga]Ga-NOTA-RW102 immunoPET imaging allowed same-day annotation of differential PD-L1 expression with specificity, while [64Cu]Cu-NOTA-ABDRW102 and [89Zr]Zr-DFO-ABDRW102 enabled longitudinal visualization of PD-L1. More importantly, a pilot clinical trial shows the safety and diagnostic value of [68Ga]Ga-NOTA-RW102 immunoPET imaging in patients with NSCLCs and its potential to predict immune-related adverse effects following PD-L1-targeted immunotherapies. CONCLUSIONS: We developed and validated a series of PD-L1-targeted tracers. Initial preclinical and clinical evidence indicates that immunoPET imaging with [68Ga]Ga-NOTA-RW102 holds promise in visualizing differential PD-L1 expression, selecting patients for PD-L1-targeted immunotherapies, and monitoring immune-related adverse effects in patients receiving PD-L1-targeted treatments. TRIAL REGISTRATION NUMBER: NCT06165874.

Understanding suicidal ideation disparity between sexual minority and heterosexual Chinese young men: a multiple mediation model of social support sources, self-esteem, and depressive symptoms.

Objectives: Although sexual minorities have reported higher levels of suicidal ideation than heterosexuals across cultures, the role of various psychosocial factors underlying this disparity among young men has been understudied, particularly in China. This study examined the multiple mediating effects of psychosocial factors between sexual orientation and suicidal ideation in Chinese sexual minority and heterosexual young men. Methods: 302 Chinese cisgender men who identified as gay or bisexual, and 250 cisgender heterosexual men (n=552, aged 18-39 years) completed an online questionnaire measuring perceived social support, self-esteem, depressive symptoms, and suicidal ideation. Results: Young sexual minority men reported significantly higher suicidal ideation and lower social support than their heterosexual peers. Structural equation modelling revealed two multiple indirect pathways. One pathway indicated that sexual orientation was indirectly related to suicidal ideation via family support and depressive symptoms. Another pathway indicated that sexual orientation was indirectly related to suicidal ideation via support from friends, self-esteem, and depressive symptoms. Conclusions: This study is among the first to examine the potentially cascading relationships between sexual orientation and psychosocial factors with suicidal ideation in a Chinese sample of young men. The findings highlight several promising psychosocial targets (i.e., improving family/friend support and increasing self-esteem) for suicide interventions among sexual minority males in China.

CENPA and BRCA1 are potential biomarkers associated with immune infiltration in heart failure and pan-cancer.

Heart failure (HF) and cancer are the two leading causes of death worldwide and affect one another in a bidirectional way. We aimed to identify hub therapeutic genes as potential biomarkers for the identification and treatment of HF and cancer. Gene expression data of heart samples from patients with ischemic HF (IHF) and healthy controls were retrieved from the GSE42955 and GSE57338 databases. Difference analysis and weighted gene co-expression network analysis (WGCNA) were used to identify key modules associated with IHF. The overlapping genes were subjected to gene and protein enrichment analyses to construct a protein-protein interaction (PPI) network, which was screened for hub genes among the overlapping genes. A total of eight hub genes were subjected to correlation, immune cell infiltration, and ROC analyses. Then we analyzed the roles of two significant genes in 33 tumor types to explore their potential as common targets in HF and cancer. A total of 85 genes were identified by WGCNA and differentially expressed gene (DEG) analyses. BRCA1, MED17, CENPA, RXRA, RXRB, SMARCA2, CDCA2, and PMS2 were identified as the hub genes with IHF. Finally, CENPA and BRCA1 were identified as potential common targets for IHF and cancer. These findings provide new perspectives for expanding our understanding of the etiology and underlying mechanisms of HF and cancer.

Ginsenoside Rh2 shifts tumor metabolism from aerobic glycolysis to oxidative phosphorylation through regulating the HIF1-α/PDK4 axis in non-small cell lung cancer.

BACKGROUND: Ginsenoside Rh2 (G-Rh2), a steroidal compound extracted from roots of ginseng, has been extensively studied in tumor therapy. However, its specific regulatory mechanism in non-small cell lung cancer (NSCLC) is not well understood. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in various malignant tumors. We investigated the impact of G-Rh2 on the malignant progression of NSCLC and how it regulated PDK4 to influence tumor aerobic glycolysis and mitochondrial function. METHOD: We examined the inhibitory effect of G-Rh2 on NSCLC through I proliferation assay, migration assay and flow cytometry in vitro. Subsequently, we verified the ability of G-Rh2 to inhibit tumor growth and metastasis by constructing subcutaneous tumor and metastasis models in nude mice. Proteomics analysis was conducted to analyze the action pathways of G-Rh2. Additionally, we assessed glycolysis and mitochondrial function using seahorse, PET-CT, Western blot, and RT-qPCR. RESULT: Treatment with G-Rh2 significantly inhibited tumor proliferation and migration ability both in vitro and in vivo. Furthermore, G-Rh2 inhibited the tumor's aerobic glycolytic capacity, including glucose uptake and lactate production, through the HIF1-α/PDK4 pathway. Overexpression of PDK4 demonstrated that G-Rh2 targeted the inhibition of PDK4 expression, thereby restoring mitochondrial function, promoting reactive oxygen species (ROS) accumulation, and inducing apoptosis. When combined with sodium dichloroacetate, a PDK inhibitor, it complemented the inhibitory capacity of PDKs, acting synergistically as a detoxifier. CONCLUSION: G-Rh2 could target and down-regulate the expression of HIF-1α, resulting in decreased expression of glycolytic enzymes and inhibition of aerobic glycolysis in tumors. Additionally, by directly targeting mitochondrial PDK, it elevated mitochondrial oxidative phosphorylation and enhanced ROS accumulation, thereby promoting tumor cells to undergo normal apoptotic processes.

Altered mucosal bacteria and metabolomics in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. AIM: This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. METHODS: The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. RESULTS: High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. CONCLUSION: This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

ImmunoPET imaging of Trop2 in patients with solid tumours.

Accurately predicting and selecting patients who can benefit from targeted or immunotherapy is crucial for precision therapy. Trophoblast cell surface antigen 2 (Trop2) has been extensively investigated as a pan-cancer biomarker expressed in various tumours and plays a crucial role in tumorigenesis through multiple signalling pathways. Our laboratory successfully developed two 68Ga-labelled nanobody tracers that can rapidly and specifically target Trop2. Of the two tracers, [68Ga]Ga-NOTA-T4, demonstrated excellent pharmacokinetics in preclinical mouse models and a beagle dog. Moreover, [68Ga]Ga-NOTA-T4 immuno-positron emission tomography (immunoPET) allowed noninvasive visualisation of Trop2 heterogeneous and differential expression in preclinical solid tumour models and ten patients with solid tumours. [68Ga]Ga-NOTA-T4 immunoPET could facilitate clinical decision-making through patient stratification and response monitoring during Trop2-targeted therapies.

An Innovative Concept of Membrane-Free Redox Flow Batteries with Near-Zero Contact Distance Between Electrodes.

Given that the ion-exchange membrane takes up more than 30% of redox flow battery (RFB) cost, considerable cost reduction is anticipated with the membrane-free design. However, eliminating the membrane/separator would expose the membrane-free RFBs to a higher risk of short-circuits, and the dendrite growth may aggravate this issue. The current strategy based on expanding distances between electrodes is proposed to address short-circuit issues. Nevertheless, this approach would decrease the energy efficiency (EE) and could not restrain dendrite growth fundamentally. Herein, an inexpensive and electron-insulating boron nitride nanosheets (BNNSs)-Nylon hybrid interlayer (BN/Nylon) is developed for general membrane-free RFBs to achieve "near-zero distance" contact between electrodes. And the Lewis acid sites (B atoms) in BNNS can interact with the Lewis base anions in electrolytes, enabling a reduced Pb2+concentration gradient. Additionally, the ultrahigh thermal conductivity and mechanical strength of BNNSs promote the uniform plating/stripping process of Pb and PbO2. Compared with conventional soluble lead RFBs, introducing BN/Nylon interlayers boosts EE by ≈38.2% at 25 mA cm-2, and extends the cycle life to 100 cycles. This innovative strategy premieres the application of the BN/Nylon interlayer concept, offering a novel perspective for the development of general membrane-free RFBs.

PFKFB3 regulates breast cancer tumorigenesis and Fulvestrant sensitivity by affecting ERα stability.

Estrogen receptor alpha (ERα) is expressed in approximately 70% of breast cancer cases and determines the sensitivity and effectiveness of endocrine therapy. 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase3 (PFKFB3) is a glycolytic enzyme that is highly expressed in a great many human tumors, and recent studies have shown that it plays a significant role in improving drug sensitivity. However, the role of PFKFB3 in regulating ERα expression and the underlying mechanism remains unclear. Here, we find by using immunohistochemistry (IHC) that PFKFB3 is elevated in ER-positive breast cancer and high expression of PFKFB3 resulted in a worse prognosis. In vitro and in vivo experiments verify that PFKFB3 promotes ER-positive breast cancer cell proliferation. The overexpression of PFKFB3 promotes the estrogen-independent ER-positive breast cancer growth. In an estrogen-free condition, RNA-sequencing data from MCF7 cells treated with siPFKFB3 showed enrichment of the estrogen signaling pathway, and a luciferase assay demonstrated that knockdown of PFKFB3 inhibited the ERα transcriptional activity. Mechanistically, down-regulation of PFKFB3 promotes STUB1 binding to ERα, which accelerates ERα degradation by K48-based ubiquitin linkage. Finally, growth of ER-positive breast cancer cells in vivo was more potently inhibited by fulvestrant combined with the PFKFB3 inhibitor PFK158 than for each drug alone. In conclusion, these data suggest that PFKFB3 is identified as an adverse prognosis factor for ER-positive breast cancer and plays a previously unrecognized role in the regulation of ERα stability and activity. Our results further explores an effective approach to improve fulvestrant sensitivity through the early combination with a PFKFB3 inhibitor.

Simultaneous photocatalytic removal of tetracycline and hexavalent chromium by BiVO4/0.6CdS photocatalyst: Insights into the performance, evaluation, calculation and mechanism.

In this study, a novel Z-scheme heterojunction on bismuth vanadium/cadmium sulfide (BiVO4/0.6CdS) was developed and evaluated for simultaneous photocatalytic removal of combined tetracycline (TC) and hexavalent chromium Cr(Ⅵ) pollution under visible light. Based on the analysis of intermediate products and theoretical calculation, the property of the intermediate products of TC degradation and the effect of built-in electric field (IEF) of composite materials on photo-generated carrier separation were illustrated. According to the experiments and evaluation results, the performance of BiVO4/0.6CdS is higher than CdS 2.83 times and 4.82 times under the visible light conditions, with the aspect of simultaneous oxidizing TC and reducing Cr(Ⅵ), respectively. The catalyst has a faster removal rate in the binary composite pollution system than the single one. Therefore, the photocatalytic degradation of TC using BiVO4/0.6CdS can reduce the toxic effect of TC on the environment. The aforementioned evaluation provides a new design strategy for Z-scheme heterojunction to simultaneous photocatalytic degradation of composite organic and inorganic pollutants.

Corosolic acid delivered by exosomes from Eriobotrya japonica decreased pancreatic cancer cell proliferation and invasion by inducing SAT1-mediated ferroptosis.

BACKGROUND: In this study, we investigated whether Exo regulate the proliferation and invasion of PC. METHODS: In this study, we isolated the Eriobotrya japonica Exo using Ultra-high speed centrifugal method. Mass spectrum were used for Exo active components analysis. PC (Capan-1 and Bxpc-3) cells proliferation, migration, and apoptosis were detected using CCK8, ethynyldeoxyuridine, transwell, wound healing, and flow cytometry analyses. We also constructed a lung metastatic mouse model and subcutaneous tumor model to illustrate the regulation effect of Exo or active components. Proteomics were used to reveal the regulatory mechanism responsible for the observed effects. RESULTS: We isolated Eriobotrya japonica Exo and found that Exo treatment significantly suppressed cell migration and proliferation in both in vivo and in vitro using Capan-1. Mass spectrum for Exo active components analysis found that Exo contains high amounts of corosolic acid (CRA). The further study found that CRA treatment inhibit the proliferation, migration, and increased cell death of both Capan-1 and Bxpc-3 cells in a concentration-dependent manner. In vivo experiments confirmed that CRA inhibited pulmonary metastasis by decreasing the number of metastatic foci. Cell proteomics analysis showed that CRA treatment induced spermidine/spermine N1-acetyltransferase 1 (SAT1)-dependent ferroptosis. Treatment with the ferroptosis suppressor ferrostatin-1 significantly reversed CRA-induced cell apoptosis. CONCLUSION: The data suggested that corosolic acid delivered by exosomes from Eriobotrya japonica decreased pancreatic cancer cell proliferation and invasion by inducing SAT1-mediated ferroptosis.

Long-term benefits of hematopoietic stem cell-based macrophage/microglia delivery of GDNF to the CNS in a mouse model of Parkinson's disease.

Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurons in various models of Parkinson's disease (PD). Cell-based GDNF gene delivery mitigates neurodegeneration and improves both motor and non-motor functions in PD mice. As PD is a chronic condition, this study aims to investigate the long-lasting benefits of hematopoietic stem cell (HSC)-based macrophage/microglia-mediated CNS GDNF (MMC-GDNF) delivery in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. The results indicate that GDNF treatment effectively ameliorated MPTP-induced motor deficits for up to 12 months, which coincided with the protection of nigral dopaminergic neurons and their striatal terminals. Also, the HSC-derived macrophages/microglia were recruited selectively to the neurodegenerative areas of the substantia nigra. The therapeutic benefits appear to involve two mechanisms: (1) macrophage/microglia release of GDNF-containing exosomes, which are transferred to target neurons, and (2) direct release of GDNF by macrophage/microglia, which diffuses to target neurons. Furthermore, the study found that plasma GDNF levels were significantly increased from baseline and remained stable over time, potentially serving as a convenient biomarker for future clinical trials. Notably, no weight loss, altered food intake, cerebellar pathology, or other adverse effects were observed. Overall, this study provides compelling evidence for the long-term therapeutic efficacy and safety of HSC-based MMC-GDNF delivery in the treatment of PD.