Mobility and environmental impact of cadmium (Cd) during weathering of carbonaceous black shales in western Hunan, China.

Carbonaceous black shale generally contains high concentration of Cd, with weathering leading to Cd release to environment. In this study, the mobility of Cd during weathering was quantified using geochemical assessment on black shale from western Hunan, China. Results suggested that Cd was heterogeneously distributed in shale profiles with concentrations ranging from 0.16 to 109.9 (mg/kg). Cd distribution was heterogeneous resulting from the parent shale inheritance and the mobility of Cd during weathering. Black shales weathered to a moderate degree with Cd mobility characterized by both enrichment in and release from weathered shales. Cd enrichment in weathered shales resulted from the re-enrichment of Cd in secondary minerals formed during the initial stage of carbonate (and phosphorite) dissolution, and the secondary stage of sulfide oxidation. The release of Cd was caused by decomposition of the secondary Cd-bearing minerals. Cadmium was extensively released during pedogenesis, and Cd release mass flux was estimated to range from 1.26 to 9.50 (g/m2) with a mean of 6.60 g/m2. Thus, black shale weathering may lead to the releasing of large amount of Cd resulting in Cd contamination to local environments.

Light-Triggered Nanozymes Remodel the Tumor Hypoxic and Immunosuppressive Microenvironment for Ferroptosis-Enhanced Antitumor Immunity.

Cancer immunotherapy holds significant promise for addressing diverse malignancies. Nevertheless, its efficacy remains constrained by the intricate tumor immunosuppressive microenvironment. Herein, a light-triggered nanozyme Fe-TCPP-R848-PEG (Fe-MOF-RP) was designed for remodeling the immunosuppressive microenvironment. The Fe-TCPP-MOFs were utilized not only as a core catalysis component against tumor destruction but also as a biocompatible delivery vector of an immunologic agonist, improving its long circulation and tumor enrichment. Concurrently, it catalyzes the decomposition of H2O2 within the tumor, yielding oxygen to augment photodynamic therapy. The induced ferroptosis, in synergy with photodynamic therapy, prompts the liberation of tumor-associated antigens from tumor cells inducing immunogenic cell death. Phototriggered on-demand release of R848 agonists stimulated the maturation of dendritic cells and reverted the tumor-promoting M2 phenotypes into adoptive M1 macrophages, which further reshaped the tumor immunosuppressive microenvironment. Notably, the nanozyme effectively restrains well-established tumors, such as B16F10 melanoma. Moreover, it demonstrates a distal tumor-inhibiting effect upon in situ light treatment. What is more, in a lung metastasis model, it elicits robust immune memory, conferring enduring protection against tumor rechallenge. Our study presents a straightforward and broadly applicable strategy for crafting nanozymes with the potential to effectively thwart cancer recurrence and metastasis.

Ferrous Selenide Stabilized Black Phosphorus Heterojunction Sonosensitizer for MR Imaging-Guided Sonodynamic Therapy of Bladder Cancer.

It is urgent to develop an alternative dynamic therapy-based method to overcome the limited efficacy of traditional therapy methods for bladder cancer and the damage caused to patients. Sonodynamic therapy (SDT) has the advantages of high tissue penetration, high spatiotemporal selectivity, and being non-invasive, representing an emerging method for eradicating deep solid tumors. However, the effectiveness of SDT is often hindered by the inefficient production of reactive oxygen species and the nondegradability of the sonosensitizer. To improve the anti-tumor effect of SDT on bladder cancer, herein, a BP-based heterojunction sonosensitizer (BFeSe2) was synthesized by anchoring FeSe2 onto BP via P-Se bonding to enhance the stability and the effect of SDT. As a result, BFeSe2 showed great cytotoxicity to bladder cancer cells under ultrasound (US) irradiation. BFeSe2 led to a notable inhibition effect on tumor growth in subcutaneous tumor models and orthotopic tumor models under US irradiation. In addition, BFeSe2 could also enhance T2-weighted magnetic resonance imaging (MRI) to achieve monitoring and guide treatment of bladder cancer. In general, BFeSe2 sonosensitizer integrates MRI functions for precise treatment, promising great clinical potential for the theranostics of bladder cancer.

Narrow Bandgap Schottky Heterojunction Sonosensitizer with High Electron-Hole Separation Boosted Sonodynamic Therapy in Bladder Cancer.

Sonodynamic therapy (SDT) is applied to bladder cancer (BC) given its advantages of high depth of tissue penetration and nontoxicity due to the unique anatomical location of the bladder near the abdominal surface. However, low electron-hole separation efficiency and wide bandgap of sonosensitizers limit the effectiveness of SDT. This study aims to develop a TiO2-Ru-PEG Schottky heterojunction sonosensitizer with high electron-hole separation and narrow bandgap for SDT in BC. Density functional theory (DFT) calculations and experiments collectively demonstrate that the bandgap of TiO2-Ru-PEG is reduced due to the Schottky heterojunction with the characteristic of crystalline-amorphous interface formed by the deposition of ruthenium (Ru) within the shell layer of TiO2. Thanks to the enhancement of oxygen adsorption and the efficient separation of electron-hole pairs, TiO2-Ru-PEG promotes the generation of reactive oxygen species (ROS) under ultrasound (US) irradiation, resulting in cell cycle arrest and apoptosis of bladder tumor cells. The in vivo results prove that TiO2-Ru-PEG boosted the subcutaneous and orthotopic bladder tumor models while exhibiting good safety. This study adopts the ruthenium complex for optimizing sonosensitizers, contributing to the progress of SDT improvement strategies and presenting a paradigm for BC therapy.

MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma.

Introduction: An effective therapeutic method to noticeably improve the prognosis of glioma patients has not been developed thus far. MAPK-activated protein kinase 2 (MAPKAPK2) is a serine/threonine kinase, which is involved in tumorigenesis, tumor growth, metastasis, and the inflammatory process. The clinical significance and molecular function of MAPKAPK2 in glioma remain unclear. Methods: MAPKAPK2 expression in human glioma tissues was detected by immunohistochemistry and analyzed from the transcriptome sequencing data in TCGA and CGGA. Prognostic nomogram was constructed to predict the survival risk of individual patients. GO and KEGG enrichment analyses were performed to analyze the function and pathways MAPKAPK2 involved. Single-cell RNA sequencing data was used to analyze the cell types in which MAPKAPK2 was enriched. Flow cytometry was used for cell cycle and apoptosis detection. The ability of cell proliferation and migration was analyzed by CCK8 and cell migration assay, respectively. Correlation analyses were performed to analyze the relationship of MAPKAPK2 with immune infiltration, immune regulators, chemokine, and chemokine receptors. Results: MAPKAPK2 was not only aberrantly upregulated in glioma tissues but also correlated with poor clinical characteristics. Moreover, MAPKAPK2 was prevalent in isocitrate dehydrogenase (IDH) wild-type and 1p/19q non-codeletion glioma cohorts and predicted poor prognosis of glioma patients. MAPKAPK2 may be involved in cell proliferation, cell migration, DNA damage repair, and immune regulation in glioma. MAPKAPK2 was enriched in microglia/macrophages and malignant tumor cells. Further investigation into cellular function revealed that inhibiting MAPKAPK2 suppressed the proliferation and migration of glioblastoma multiforme (GBM) cells in vitro. The inhibition of MAPKAPK2 significantly induced the G1 cell cycle arrest and cell apoptosis of GBM cells. Consistent with the enriched function of MAPKAPK2 in immune regulation, MAPKAPK2 was correlated with immune cell infiltration in glioma tissues. Mechanistically, a series of immune regulators, immunomodulatory chemokine, and chemokine receptors were positively correlated with MAPKAPK2 expression. Discussion: Our findings provide evidence of the clinical relevance of MAPKAPK2 in prognosis evaluation of glioma patients and highlight the underlying significance of MAPKAPK2 in glioma therapy.

Hydronium Intercalation Enables High Rate in Hexagonal Molybdate Single Crystals.

Rapid proton transport in solid-hosts promotes a new chemistry in achieving high-rate Faradaic electrodes. Exploring the possibility of hydronium intercalation is essential for advancing proton-based charge storage. Nevertheless, this is yet to be revealed. Herein, a new host is reported of hexagonal molybdates, (A2 O)x ·MoO3 ·(H2 O)y (A = Na+ , NH4 + ), and hydronium (de)intercalation is demonstrated with experiments. Hexagonal molybdates show a battery-type initial reduction followed by intercalation pseudocapacitance. Fast rate of 200 C (40 A g-1 ) and long lifespan of 30 000 cycles are achieved in electrodes of monocrystals even over 200 µm. Solid-state nuclear magnetic resonance confirms hydronium intercalations, and operando measurements using electrochemical quartz crystal microbalance and synchrotron X-ray diffraction disclose distinct intercalation behaviours in different electrolyte concentrations. Remarkably, characterizations of the cycled electrodes show nearly identical structures and suggest equilibrium products are minimally influenced by the extent of proton solvation. These results offer new insights into proton electrochemistry and will advance correlated high-power batteries and beyond.

BioKA: a curated and integrated biomarker knowledgebase for animals.

Biomarkers play an important role in various area such as personalized medicine, drug development, clinical care, and molecule breeding. However, existing animals' biomarker resources predominantly focus on human diseases, leaving a significant gap in non-human animal disease understanding and breeding research. To address this limitation, we present BioKA (Biomarker Knowledgebase for Animals, https://ngdc.cncb.ac.cn/bioka), a curated and integrated knowledgebase encompassing multiple animal species, diseases/traits, and annotated resources. Currently, BioKA houses 16 296 biomarkers associated with 951 mapped diseases/traits across 31 species from 4747 references, including 11 925 gene/protein biomarkers, 1784 miRNA biomarkers, 1043 mutation biomarkers, 773 metabolic biomarkers, 357 circRNA biomarkers and 127 lncRNA biomarkers. Furthermore, BioKA integrates various annotations such as GOs, protein structures, protein-protein interaction networks, miRNA targets and so on, and constructs an interactive knowledge network of biomarkers including circRNA-miRNA-mRNA associations, lncRNA-miRNA associations and protein-protein associations, which is convenient for efficient data exploration. Moreover, BioKA provides detailed information on 308 breeds/strains of 13 species, and homologous annotations for 8784 biomarkers across 16 species, and offers three online application tools. The comprehensive knowledge provided by BioKA not only advances human disease research but also contributes to a deeper understanding of animal diseases and supports livestock breeding.

Preparation, purification, and biochemical of fat-degrading bacterial enzymes from pig carcass compost and its application.

BACKGROUND: A lot of kitchen waste oil is produced every day worldwide, leading to serious environmental pollution. As one of the environmental protection methods, microorganisms are widely used treating of various wastes. Lipase, as one of the cleaning agents can effectively degrade kitchen waste oil. The composting process of pig carcasses produces many lipase producing microorganisms, rendering compost products an excellent source for isolating lipase producing microorganisms. To our knowledge, there are no reports isolating of lipase producing strains from the high temperature phase of pig carcass compost. METHODOLOGY: Lipase producing strains were isolated using a triglyceride medium and identified by 16S rRNA gene sequencing. The optimal fermentation conditions for maximum lipase yield were gradually optimized by single-factor tests. The extracellular lipase was purified by ammonium sulfate precipitation and Sephadex G-75 gel isolation chromatography. Amino acid sequence analysis, structure prediction, and molecular docking of the purified protein were performed. The pure lipase's enzymatic properties and application potential were evaluated by characterizing its biochemical properties. RESULTS: In this study, a lipase producing strain of Bacillus sp. ZF2 was isolated from pig carcass compost products, the optimal fermentation conditions of lipase: sucrose 3 g/L, ammonium sulfate 7 g/L, Mn2+ 1.0 mmol/L, initial pH 6, inoculum 5%, temperature 25 ℃, and fermentation time 48 h. After purification, the specific activity of the purified lipase reached 317.59 U/mg, a 9.78-fold improvement. Lipase had the highest similarity to the GH family 46 chitosanase and molecular docking showed that lipase binds to fat via two hydrogen bonds at Gln146 (A) and Glu203 (A). Under different conditions (temperature, metal ions, organic solvents, and surfactants), lipase can maintain enzymatic activity. Under different types of kitchen oils, lipase has low activity only for 'chicken oil', in treating other substrates, the enzyme activity can exceed 50%. CONCLUSIONS: This study reveals the potential of lipase for waste oil removal, and future research will be devoted to the application of lipase.

Model-free fast integral terminal sliding-mode control method based on improved fast terminal sliding-mode observer for PMSM with unknown disturbances.

This paper presents a novel model-free fast integral terminal sliding-mode control (MFFITSMC) method based on an improved fast terminal sliding-mode observer (IFTSMO) for permanent magnet synchronous motor (PMSM) drive system, which can effectively eliminate the impact caused by unknown disturbances, such as parameter perturbations and external disturbances. The PMSM mathematical model with unknown disturbances is first established, and the ultra-local model (ULM) of the PMSM speed loop is constructed. Next, the model-free fast integral terminal sliding-mode controller is designed in the speed loop based on the ULM. Then, the IFTSMO is designed to precisely estimate the unknown term of the ULM, and the estimated unknown term is fed back to the MFFITSMC controller to perform compensation for unknown disturbances in real time. Finally, compared with the proportional-integral (PI) control method and the conventional model-free sliding-mode control (MFSMC) method, the results of simulations and experiments demonstrate that the presented MFFITSMC method reduces the dependence on the precise model and achieves the purpose of anti-disturbance control of the PMSM drive system.

Teaching of silver diamine fluoride for the management of dental caries and hypersensitivity - situation in the Southeast Asia dental schools.

BACKGROUND: Using silver diamine fluoride (SDF) for caries management has raised dentists' interests in Southeast Asia (SEA). However, information about the teaching of SDF in dental schools in SEA is limited. Therefore, this survey aimed to describe the extent to which SDF had been introduced into the education of undergraduate students in the dental schools in SEA. METHODS: An online questionnaire survey was conducted on the duration, method, contents, and barriers regarding the teaching of SDF. Teachers in charge of undergraduate program in pediatric dentistry and those in community dentistry in all the 90 dental schools in SEA were approached and we required each department to reply once only. Descriptive statistics and Chi-square test were used to describe and assess the differences between the two departments in the teaching of SDF. RESULTS: A total of 81 responses from the departments of 49 schools were received, giving a school-level response rate of 54% (49/90). SDF was taught in the undergraduate program in 86% (42/49) of the respondent schools, and 50% (21/42) of these schools had included SDF in the teaching for five or more years. Almost all (98%) of the departments taught SDF through lectures. Furthermore, 55% of them adopted SDF in clinical practice. Regarding the teaching content, the use of SDF for arresting cavitated caries lesion was the most commonly covered (82-97%), followed by for arresting early noncavitated lesions (69-82%), for preventing new caries development (66-79%) and for treating dental hypersensitivity (77%). There were variations in the post-treatment instruction taught. For the departments not teaching SDF, the most common reason (10/19, 53%) was that SDF was not available. CONCLUSION: SDF is covered in the undergraduate program in most of the dental schools in SEA. The use of SDF to arrest cavitated caries lesions in primary teeth is usually taught. However, other applications of SDF, such as for prevention of caries and treatment of dental hypersensitivity, are less commonly mentioned in the teaching.

Distribution, source and contamination of rare earth elements in sediments from lower reaches of the Xiangjiang River, China.

Rare earth elements (REEs) are emerging micropollutants in aquatic environments. In this study, concentrations of REEs and major elements, and mineralogical compositions of sediments from lower reaches of the Xiangjiang River (China) were analyzed using ICP-MS technique. The results suggested that sediments were characterized by terrigenous compositions TiO2, SiO2, Al2O3, K2O, Na2O and P2O, and contained high concentrations of REEs with mean total REE concentrations (∑REE) of 318.7 mg/kg. REEs were moderately enriched in upper river sediments, and slightly or less enriched in downriver sediments. The normalized REE distribution pattern for sediments was characterized by flat shalelike and Eu depleted V-shape REE patterns, which indicated REEs in sediments were lithologically contributed from sedimentary rocks and granites distributed in the watershed respectively. REEs in sediments were hosted mainly in Fe-Mn oxides, and sulfide and organic matters that were characterized by middle REEs (MREE) enrichments relative to light REEs (LREE) and heavy REEs (HREE), and the distribution and differentiation of REEs in sediments were controlled by clays, Fe-Mn oxides, organic matters and finer grains; and also by accessory minerals (e.g., zircon) from granite. The distribution features of REEs in sediments and BCR extraction results suggested that the sediment REE enrichment resulted from additional REE input from anthropogenic sources, including those in discharges from sulfide-ore smelting industries at Zhuzhou city and from phosphate fertilizer plants at Xiangtan city along the river. Thus, sediments were contaminated with REEs in moderate degree in upper river area, and REE contamination was then formed by superimposing anthropogenic REEs on lithological residues. Finally, concentrations of Ce > 100 mg/kg, Gd > 8.12 mg/kg, ∑REE >274.9 mg/kg, ∑LREE >252.3 mg/kg and ∑HREE >28.8 mg/kg here were recommended as the REE contamination levels that represented as REE indices for identifying and rating REE contamination in this mining impacted river.

Efficacy and feasibility of Apatinib and S-1 as a novel oral induction therapy in locally advanced head and neck squamous cell carcinoma: an exploratory phase 2 open-label, single-arm trial.

Objectives: The current standard nonsurgical treatment for locally advanced head and neck squamous cell cancer (LA-HNSCC) is concomitant chemoradiotherapy (CRT). Neoadjuvant chemotherapy combined with CRT has been explored in HNSCC patients and is an acceptable strategy. However, the occurrence of adverse events (AEs) restricts its application. We conducted a clinical study to explore the efficacy and feasibility of a novel induction therapy with orally administered apatinib and S-1 in LA-HNSCC. Materials and methods: This nonrandomized, single-arm, prospective clinical trial included patients with LA-HNSCCs. The eligibility criteria included histologically or cytologically confirmed HNSCC, with at least one radiographically measurable lesion detected by magnetic resonance imaging (MRI) or computerized tomography (CT) scan, age 18-75 years, and a diagnosis of stage III to IVb according to the 7th edition of the American Joint Committee of Cancer (AJCC). Patients received induction therapy with apatinib and S-1 for three cycles (3 weeks/cycle). The primary endpoint of this study was the objective response rate (ORR) to induction therapy. The secondary endpoints included progression-free survival (PFS), overall survival (OS), and AEs during induction treatment. Results: From October 2017 to September 2020, 49 patients with LA-HNSCC were screened consecutively and 38 were enrolled. The median age of the patients was 60 years (range, 39-75). Thirty-three patients (86.8%) had stage IV disease according to the AJCC staging system. The ORR after induction therapy was 97.4% (95% confidence interval [CI]: 86.2%-99.9%). the 3-year OS rate was 64.2% (95% CI: 46.0%-78.2%) and 3-year PFS was 57.1% (95% CI: 40.8%-73.6%). The most common AEs during induction therapy were hypertension and hand-foot syndrome, which were manageable. Conclusion: Apatinib combined with S-1 as novel induction therapy for LA-HNSCC patients resulted in a higher-than-anticipated ORR and manageable adverse effects. With the associated safety profile and preferable oral administration route, apatinib combined with S-1 is an attractive exploratory induction regimen in outpatient settings. However, this regimen failed to show a survival benefit. Clinical trial registration: https://clinicaltrials.gov/show/NCT03267121, identifier NCT03267121.

Development of the Emoji Faces Pain Scale and Its Validation on Mobile Devices in Adult Surgery Patients: Longitudinal Observational Study.

BACKGROUND: Measuring pain on digital devices using classic unidimensional pain scales such as the visual analog scale (VAS), numerical rating scale (NRS), and faces pain scale (FPS) has been proven to be reliable and valid. Emoji are pictographs designed in colorful form following the Unicode standard. It could be more beneficial to use emoji as faces of FPS on digital devices because emoji can easily fit on most devices and emoji are open-source so no approval would be needed before use. With a concise and user-friendly design, the emoji faces pain scale (Emoji-FPS) might be more generalizable to a wider population and more preferred by digital device users. OBJECTIVE: This study was designed to develop an Emoji-FPS as well as to evaluate its reliability, validity, and preference on mobile devices in adult patients who underwent surgery. METHODS: A modified Delphi technique with 2 rounds of web-based surveys was applied to obtain panelists' consensus on the sequence of emoji that can best represent 6 levels of pain. The initial candidate sequences of emoji for the Delphi process were constructed referring to 2 well-validated FPSs (Wong-Baker FACES pain rating scale [Wong-Baker FACES] and faces pain scale-revised [FPS-R]). Then, a prospective cohort of patients scheduled to receive perianal surgery was recruited and asked to complete a web-based questionnaire on a mobile device at 5 time points (before surgery [T1], wake up after surgery [T2], 4 hours after surgery [T3], the second day after surgery [T4], and 15 minutes after T4 [T5]). The 4 well-validated pain scales (NRS, VAS, Wong-Baker FACES, and FPS-R) were used as reference scales. RESULTS: After 2 rounds of surveys on 40 Delphi panelists, an Emoji-FPS was finally determined to represent 6 pain levels (0, 2, 4, 6, 8, and 10) from "no hurt" to "hurts worst." For validation, 300 patients were recruited and 299 were analyzed, the mean age of whom was 38.5 (SD 10.5) years, and 106 (35.5%) were women. For concurrent validity, the Emoji-FPS was highly correlated with 4 reference scales with Spearman correlation coefficient ρ ranging from 0.91 to 0.95. Excellent agreements were observed between 4 versions of Emoji-FPS (iOS, Android, Microsoft, and OpenMoji), with weighted κ coefficients ranging from 0.96 to 0.97. For discriminant validity, patients' mean preoperative Emoji-FPS score (T1) was significantly higher than their postoperative Emoji-FPS score (T4) with a difference of 1.4 (95% CI 1.3-1.6; P<.001). For test-retest reliability, Emoji-FPS scores measured at T4 and T5 were highly correlated with a ρ of 0.91. The Emoji-FPS was mostly preferred, followed by the Wong-Baker FACES, FPS-R, NRS, and VAS. CONCLUSIONS: The Emoji-FPS is reliable and valid compared with traditional pain scales in adult surgery patients.

Adjuvant PD-1 antibody in recurrent, previously irradiated oral cavity cancer treated with salvage surgery.

Objectives: The role of re-irradiation after salvage surgery for recurrent oral cavity cancer (OCC) is controversial. We evaluated the efficacy and safety of adjuvant toripalimab (PD-1 antibody) in this patient setting. Materials and methods: In this phase II study, patients after salvage surgery with OCC occurring in an area of previously irradiated were enrolled. Patients received toripalimab 240 mg once every 3 weeks for 12 months, or combined with S-1 orally for 4-6 cycles. The primary endpoint was 1-year progression-free survival (PFS). Results: Between April 2019 and May 2021, 20 patients were enrolled. Sixty percent patients had ENE or positive margins, 80% were restaged as stage IV, and 80% were previously treated with chemotherapy. The 1-year PFS and overall survival (OS) were 58.2%, and 93.8%, respectively, for patients with CPS ≥ 1, which was significantly better than those of the real-world reference cohort (p = 0.001 and 0.019). No grade 4-5 toxicities were reported, and only one patient experienced grade 3 immune related adrenal insufficiency and discontinued treatment. The 1-year PFS and OS were significantly different for patients with CPS < 1, CPS 1-19 and CPS ≥ 20 (p = 0.011 and 0.017, respectively). The peripheral blood B cell proportion was also correlated with PD in 6 months (p = 0.044). Conclusion: Adjuvant toripalimab or combine with S-1 after salvage surgery showed improved PFS compared with a real-world reference cohort in recurrent, previously irradiated OCC, and favorable PFS were observed in patients with a higher CPS and peripheral B cell proportion. Further randomized trials are warranted.

MAPK4 predicts poor prognosis and facilitates the proliferation and migration of glioma through the AKT/mTOR pathway.

BACKGROUND: Mitogen-activated protein kinase 4 (MAPK4) is an atypical member of the mitogen-activated protein kinase (MAPK) family. We report here that MAPK4 is overexpressed in glioma. The clinical significance, biological roles and underlying molecular mechanisms through which MAPK4 acts in glioma remain unclear. METHODS: Analysis of MAPK4 expression and associated survival in glioma patients was performed based on data obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases and confirmed in human glioma tissue by immunohistochemistry. MAPK4 function and pathway enrichment were analyzed through Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO). The viability and migration ability of MAPK4-silenced glioblastoma multiforme (GBM) cells were evaluated using CCK8 and transwell assays, respectively, and cell cycle and apoptosis analyses were performed using flow cytometry. Immunoblotting was used to analyze the protein level in MAPK4 knockdown glioma cells. We also analyzed the correlation of MAPK4 expression with immune infiltration and immune checkpoints in glioma. RESULTS: MAPK4 was overexpressed in IDH wild-type (wt) and 1p/19q non-codeletion gliomas. MAPK4 expression predicted poor prognosis of glioma patients. MAPK4 was significantly related to functional states, including stemness, metastasis, cell cycle, differentiation and proliferation, in glioma at single-cell resolution. MAPK4 silencing inhibited proliferation and migration and induced G1 cell cycle arrest in glioma cells via the AKT/mTOR pathway. In vivo, MAPK4 knockdown markedly suppressed the growth of primary glioma. In addition, MAPK4 expression correlated negatively with the infiltration of plasmacytoid DC cells, CD8+ T cells and T helper cells. Moreover, MAPK4 expression correlated positively with expression of the main immunoinhibitor checkpoint molecules and some chemokines in glioma. CONCLUSION: MAPK4 functions as a prognostic indicator in glioma and promotes the proliferation and migration of GBM cells through the AKT/mTOR pathway. MAPK4 may participate in immune infiltration and the expression of immune checkpoints in the glioma microenvironment.

Designing Intelligent Nanomaterials to Achieve Highly Sensitive Diagnoses and Multimodality Therapy of Bladder Cancer.

Bladder cancer (BC) is among the most common malignant tumors of the genitourinary system worldwide. In recent years, the rate of BC incidence has increased, and the recurrence rate is high, resulting in poor quality of life for patients. Therefore, how to develop an effective method to achieve synchronous precise diagnoses and BC therapies is a difficult problem to solve clinically. Previous reports usually focus on the role of nanomaterials as drug delivery carriers, while a summary of the functional design and application of nanomaterials is lacking. Summarizing the application of functional nanomaterials in high-sensitivity diagnosis and multimodality therapy of BC is urgently needed. This review summarizes the application of nanotechnology in BC diagnosis, including the application of nanotechnology in the sensoring of BC biomarkers and their role in monitoring BC. In addition, conventional and combination therapies strategy in potential BC therapy are analyzed. Moreover, different kinds of nanomaterials in BC multimodal therapy according to pathological features of BC are also outlined. The goal of this review is to present an overview of the application of nanomaterials in the theranostics of BC to provide guidance for the application of functional nanomaterials to precisely diagnose and treat BC.

Accurate diagnosis of prostate cancer with CRISPR-based nucleic acid test strip by simultaneously identifying PCA3 and KLK3 genes.

Although serum prostate specific antigen (PSA) testing could decrease the morality of prostate cancer (PCa), its low specificity usually led to misdiagnosis due to prostatitis or benign prostatic hyperplasia (BPH). Prostate cancer antigen 3 (PCA3) as an alternative prostate tumor-specificity biomarker could be used to increase the specificity of PCa diagnosis, however, it usually required sophisticated operation and expensive equipment for routine detection. Herein, we constructed an early detection platform for prostate cancer with reverse transcriptase-recombinase aided amplification (RT-RAA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 based nucleic acid test strip. The amplicons of PCA3 and kallikrein related peptidase 3 (KLK3) gene, which amplified simultaneously by single-amplification unit of RT-RAA were specifically recognized by Cas9-sgRNA and visual on the nucleic acid test strip by naked eyes without instruments. Simultaneously detection of PCA3 and KLK3 gene could improve specificity and accuracy of the diagnosis but avoid mutual interference. In addition, the platform presented a detection limit of 500 fg/µL and 50 fg/µL in PCA3 and KLK3 gene, respectively. Furthermore, the analysis result of signal ratio of PCA3 to KLK3 gene of urine and peripheral blood specimens from 32 men with suspected prostate cancer on test strips illustrated that the area under the curve values of urine and peripheral blood specimens were 0.998 and 1.0 respectively. In summary, our study highlighted a facile strategy to design an accurate prostate cancer gene detection platform which had the potential to conduct prostate cancer early detection in the resource-limited or other point-of-care testing (POCT) environments.

Transcriptome profiling of Microbacterium resistens MZT7 reveals mechanisms of 17ß-estradiol response and biotransformation.

17ß-estradiol (E2) pollution has attracted much attention, and the existence of E2 poses certain risks to the environment and human health. However, the mechanism of microbial degradation of E2 remains unclear. In this study, the location of E2-degrading enzymes was investigated, and transcriptome analysis of Microbacterium resistens MZT7 (M. resistens MZT7) exposed to E2. The degradation of E2 by M. resistens MZT7 was via the biological action of E2-induced intracellular enzymes. With the RNA sequencing, we found 1109 differentially expressed genes (DEGs). Among them, 773 genes were up-regulated and 336 genes were down-regulated. The results of the RNA sequencing indicated the DEGs were related to transport, metabolism, and stress response. Genes for transport, transmembrane transport, oxidoreductase activity, ATPase activity, transporter activity and quorum sensing were up-regulated. Genes for the tricarboxylic acid cycle, ribosome, oxidative phosphorylation and carbon metabolism were down-regulated. In addition, heterologous expression of one enzymes efficiently degraded E2. These findings provide some new insights into the molecular mechanism of biotransformation of E2 by M. resistens MZT7.

Simultaneous removal of NO, SO2 and Hg0 with the WDRMRS.

Micro-nanobubbles can spontaneously generate hydroxyl free radicals (OH). Urea is a cheap reductant and can react with NOx species, and their products are nontoxic and harmless N2, CO2 and H2O. In this study, a Wet Direct Recycling Micro-nanobubble Flue Gas Multi-pollutants Removal System (WDRMRS) was developed for the simultaneous removal of NO, SO2 and Hg0. In this system, a micro-nanobubble generator (MNBG) was used to produce a micro-nanobubble gas-liquid dispersion system (MNBGLS) through recycling the urea solution from the reactor and the simulated flue gas composed of N2, NO, SO2 and Hg0. The MNBGLS, which has a large gas-liquid dispersion interface, was recycled continuously from the MNBG to the reactor, thus achieving cyclic absorption of various pollutants. All of the investigated parameters, including the initial pH and temperature of the absorbent as well as the concentrations of urea, NO and SO2 had significant effects on the NO removal efficiency but did not significantly affect the SO2 removal efficiency, whereas only the initial solution pH and NO concentration affected the Hg0 removal efficiency. The analysis results of the reaction mechanism showed that ·OH played a critical role in the removal of various pollutants. After the treatment by this system, the main removal products were Hg0 sediment, SO42- and NH4+ which could be easily recycled. The use of this system (MNBGLS) for the simultaneous removal of NO, SO2 and Hg0 is a new technology application and research. Recycling process based on MNBGLS succeeded in simultaneously removing NO, SO2 and Hg0. The system (MNBGLS) can provide a reference for commercial applications. The removal products are relatively simple and beneficial to recycling, which can reduce the cost of waste gas treatment.

Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage.

Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanoparticles (CNPs) were selected from CeO2 with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce3+ to Ce4+ could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNPS against oxalate-induced damage and the effect of CNPS on calcium oxalate crystallization were studied. CNPS could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNPS can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNPS as a potential for clinical prevention of crystalline kidney injury and crystal deposition.