Interventions for Postextubation Dysphagia in Critically Ill Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: This review evaluates the efficacy and safety of dysphagia interventions for patients with prolonged endotracheal intubation (⩾48 h) in critical care units. DATA SOURCES: We systematically searched PubMed, Cochrane Library, Medline, Embase, OVID, CINAHL, Wanfang (China), CNKI (China), and ProQuest Dissertations for studies published up to December 31, 2023. STUDY SELECTION: Inclusion criteria encompassed randomized controlled trials (RCTs), quasi-randomized trials, and cohort studies comparing dysphagia rehabilitation - such as swallowing stimulation, swallowing and respiratory muscle exercise, and neuromuscular electrical stimulation - with standard care or no treatment. The primary outcomes assessed were dysphagia severity, time to resume oral intake, and incidence of aspiration and aspiration pneumonia. DATA EXTRACTION: Detailed information on study design, setting, participant demographics, interventions, and outcomes was systematically extracted. DATA SYNTHESIS: Our analysis included ten studies with a total of 1031 participants. The findings demonstrate a significant reduction in dysphagia severity, time to oral intake and the risk of aspiration pneumonia, and an improvement in quality of life among patients receiving swallowing therapy. However, no substantial difference was found in nutritional status. Limited data availability necessitated a descriptive presentation of outcomes like the risk of aspiration, ICU/hospital stay duration, pharyngeal/oral residue severity, and intervention-related adverse events. CONCLUSION: The current evidence for the effectiveness of dysphagia interventions in critically ill patients with prolonged endotracheal intubation is limited. There is a pressing need for future research, particularly high-quality RCTs employing standardized outcome measures, to substantiate these findings.

circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA.

Circular RNAs (circRNAs) play crucial biological functions in various tumors, including bladder cancer (BCa). However, the roles and underlying molecular mechanisms of circRNAs in the malignant proliferation of BCa are yet unknown. CircKDM1A was observed to be downregulated in BCa tissues and cells. Knockdown of circKDM1A promoted the proliferation of BCa cells and bladder xenograft growth, while the overexpression of circKDM1A exerts the opposite effect. The dual-luciferase reporter assay revealed that circKDM1A was directly bound to miR-889-3p, acting as its molecular sponge to downregulate CPEB3. In turn, the CPEB3 was bound to the CPE signal in p53 mRNA 3'UTR to stabilize its expression. Thus, circKDM1A-mediated CPEB3 downregulation inhibits the stability of p53 mRNA and promotes BCa malignant progression. In conclusion, circKDM1A functions as a tumor suppressor in the malignant proliferation of BCa via the miR-889-3p/CPEB3/p53 axis. CircKDM1A may be a potential prognostic biomarker and therapeutic target of BCa.

Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification.

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.

Conjugation of sulpiride with a cell penetrating peptide to augment the antidepressant efficacy and reduce serum prolactin levels.

Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting as a dopamine D2 receptor antagonist and possessing anti-inflammatory properties, exhibits limited ability to penetrate the blood brain barrier (BBB). This weak penetration hampers its inhibitory effect on prolactin release in the pituitary gland, consequently leading to hyperprolactinemia. In order to enhance the central nervous system efficacy of sulpiride and reduce serum prolactin levels, we covalently linked sulpiride to VPALR derived from the nuclear DNA repair protein ku70. In vivo study on depressive mice using intraperitoneal injection of VPALR-SUL demonstrated a significant increase in struggle time and total distance compared to those treated with only sulpiride while also reducing serum prolactin concentration. The pharmacokinetic study results showed that VPALR-SUL prolonged half-life and increased bioavailability. In conclusion, VPALR-SUL exhibited potential for enhancing sulpiride transport across the BBB, augmenting its antidepressant effects, and reducing serum prolactin levels. This study laid a foundation for improving sulpiride delivery and developing novel antidepressants.

Non-Equivalent Donor-Acceptor Type Polymers as Dopant-Free Hole-Transporting Materials for Perovskite Solar Cells.

Electron donor (D)-electron acceptor (A) type conjugated polymers present bright prospects as dopant-free hole-transporting materials (HTMs) for perovskite solar cells (PVSCs). Most of the reported D-A polymeric HTMs contain equivalent amounts of D and A units, while the appropriate excess proportion of D units could optimize the aggregation state of polymer chains and improve the hole transport properties of the polymers. Herein, a non-equivalent D-A copolymerization strategy was utilized to develop three indacenodithiophene-benzotriazole-based polymeric HTMs for PVSCs, named as F-10, F-15, and F-20, and the equivalent D-A polymer F-00 was studied in parallel. Effects of D : A ratio on the hole transport properties of these D-A type polymeric HTMs, including energy level, molecular stacking, hole mobility, and surface morphology, were investigated by theoretical simulation and test analysis. F-15 performed best due to the appropriate D : A ratio, endowing the PVSCs a champion power conversion efficiency of 20.37 % with high stability, which confirms the fine-tuning D : A ratio via non-equivalent D-A copolymerization strategy is very helpful to construct D-A type polymeric HTMs for high-performance PVSCs.

A GC-MS-based untargeted metabolomics approach for comprehensive metabolic profiling of mycophenolate mofetil-induced toxicity in mice.

Background: Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid, is widely used for maintenance immunosuppression in transplantation. The gastrointestinal toxicity of MMF has been widely uncovered. However, the comprehensive metabolic analysis of MMF-induced toxicity is lacking. This study is aimed to ascertain the metabolic changes after MMF administration in mice. Methods: A total of 700 mg MMF was dissolved in 7 mL dimethyl sulfoxide (DMSO), and then 0.5 mL of mixture was diluted with 4.5 mL of saline (100 mg/kg). Mice in the treatment group (n = 9) were given MMF (0.1 mL/10 g) each day via intraperitoneal injection lasting for 2 weeks, while those in the control group (n = 9) received the same amount of blank solvent (DMSO: saline = 1:9). Gas chromatography-mass spectrometry was utilized to identify the metabolic profiling in serum samples and multiple organ tissues of mice. The potential metabolites were identified using orthogonal partial least squares discrimination analysis. Meanwhile, we used the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (http://www.kegg.jp) to depict the metabolic pathways. The percentages of lymphocytes in spleens were assessed by multiparameter flow cytometry analysis. Results: Compared to the control group, we observed that MMF treatment induced differential expression of metabolites in the intestine, hippocampus, lung, liver, kidney, heart, serum, and cortex tissues. Subsequently, we demonstrated that multiple amino acids metabolism and fatty acids biosynthesis were disrupted following MMF treatment. Additionally, MMF challenge dramatically increased CD4+ T cell percentages but had no significant influences on other types of lymphocytes. Conclusion: MMF can affect the metabolism in various organs and serum in mice. These data may provide preliminary judgement for MMF-induced toxicity and understand the metabolic mechanism of MMF more comprehensively.

Paeoniflorin attenuates cuproptosis and ameliorates left ventricular remodeling after AMI in hypobaric hypoxia environments.

This study investigates the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling following acute myocardial infarction (AMI) under conditions of hypobaric hypoxia. Left ventricular remodeling post-AMI plays a pivotal role in exacerbating heart failure, especially at high altitudes. Using a rat model of AMI, the study aimed to evaluate the cardioprotective potential of PF under hypobaric hypoxia. Ninety male rats were divided into four groups: sham-operated controls under normoxia/hypobaria, an AMI model group, and a PF treatment group. PF was administered for 4 weeks after AMI induction. Left ventricular function was assessed using cardiac magnetic resonance imaging. Biochemical assays of cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis were performed. Results demonstrated PF significantly improved left ventricular function and remodeling after AMI under hypobaric hypoxia. Mechanistically, PF decreased FDX1/DLAT expression and serum copper while increasing pyruvate. It also attenuated apoptosis, inflammation, and fibrosis by modulating Bcl-2, Bax, NLRP3, and oxidative stress markers. Thus, PF exhibits therapeutic potential for left ventricular remodeling post-AMI at high altitude by inhibiting cuproptosis, inflammation, apoptosis and fibrosis. Further studies are warranted to optimize dosage and duration and elucidate PF's mechanisms of action.

Plasma campesterol and ABCG5/ABCG8 gene loci on the risk of cholelithiasis and cholecystitis: evidence from Mendelian randomization and colocalization analyses.

The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.

A sensitive and specific LC-MS/MS method for determination of a novel antihypertensive peptide FR-6 in rat plasma and pharmacokinetic study.

The investigation of peptide drugs has become essential in the development of innovative medications for hypertension. In this study, a sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the plasma concentration and stability of the antihypertensive peptide FR-6 in rats. An isotopically labeled peptide (with an unchanged sequence) was utilized as an internal standard (IS) for validation purposes. Subsequently, this assay was employed to examine the pharmacokinetics of different administration methods (tail vein and gavage) in Sprague Dawley (SD) rats. Extracted plasma samples underwent sample preparation through methanol protein precipitation, followed by elution of FR-6 on Wondasil C18 Superb column (4.6 × 150 mm, 5 µm), using a mobile phase consisting of formic acid (0.1%) in water (A) and formic acid (0.125%)-ammonium formate (2 mM) in methanol (B). Ion pairs corresponding to FR-6 and IS were monitored via multiple reaction monitoring (MRM) under positive ion mode: m/z 400.7 â†’ 285.1 for FR-6 and m/z 406.1 â†’ 295.1 for IS detection respectively. The method exhibited excellent linearity with respect to FR-6 concentrations. In addition, the inter-day and intra-day precision were 0.61-6.85% and 1.76-11.75%; the inter-day and intra-day accuracy were -7.28-0.13% and -7.20-2.28%, respectively. In conclusion, the matrix effect, extraction recovery, and stability data were validated according to FDA recommended acceptance criteria for bioanalytical methods. This validated method serves as a reliable tool for determining the concentration of antihypertensive peptide FR-6, and has been successfully applied in pharmacokinetic studies involving rats.

Graphyne-based 3D porous structure and its sandwich-type graphene structure for alkali metal ion battery anode materials.

In order to develop candidate materials for more metal ion battery anodes, a three-dimensional (3D) porous structure 3D-PGY was designed based on graphyne, and a sandwich structure graphene/PGY/graphene (G/PGY/G) was constructed by adjusting the distance between two layers of graphene with 3D-PGY as the middle layer. Systematic calculations have shown that 3D-PGY is thermally and mechanically stable even at temperatures up to 1000 K. Li can migrate in multiple diffusion directions in two structures because of its smaller radius while Na and K ions can only migrate through the larger pores. The energy barriers of Li, Na and K ions in 3D-PGY are 0.18, 0.43 and 0.27 eV respectively. After forming the sandwich structure with graphene, the minimum energy barriers of Li, Na and K ions are decreased to 0.12, 0.37 and 0.24 eV, respectively. As the anode for Li, Na, and K ion batteries, the theoretical specific capacities of 3D-PGY are about 558 mA h g-1, and the average open circuit voltages of 3D-PGY and G/PGY/G are about 0.48/0.52/0.29 and 1.08/1.04/1.39 V, respectively. Finally, using ab initio molecular dynamics simulations, the diffusion coefficients for 3D-PGY at different temperatures, as well as for G/PGY/G at 400 K were obtained. The Li, Na and K ions in both structures can diffuse rapidly and have good rate capabilities. These excellent performances show that the graphyne-based 3D porous structure and its sandwich-type graphene structure are very promising for the development of new battery materials.

Arresting the G2/M phase empowers synergy in magnetic nanomanipulator-based cancer mechanotherapy and chemotherapy.

Using mechanical cues for cancer cells can realize precise control and efficient therapeutic effects. However, the cell cycle-specific response for dynamic mechanical manipulation is barely investigated. Here, RGD-modified iron oxide nanomanipulators were utilized as the intracellular magneto-mechanical transducers to investigate the mechanical impacts on the cell cycle under a dynamic magnetic field for cancer treatment. The G2/M phase was identified to be sensitive to the intracellular magneto-mechanical modulation with a synergistic treatment effect between the pretreatment of cell cycle-specific drugs and the magneto-mechanical destruction, and thus could be an important mechanical-targeted phase for regulation of cancer cell death. Finally, combining the cell cycle-specific drugs with magneto-mechanical manipulation could significantly inhibit glioma and breast cancer growth in vivo. This intracellular mechanical stimulus showed cell cycle-dependent cytotoxicity and could be developed as a spatiotemporal therapeutic modality in combination with chemotherapy drugs for treating deep-seated tumors.

Discovering Electrochemistry with an Electrochemistry-Informed Neural Network (ECINN).

Machine learning is increasingly integrated into chemistry research by guiding experimental procedures, correlating structure and function, interpreting large experimental datasets, to distill scientific insights that might be challenging with traditional methods. Such applications, however, largely focus on gaining insights via big data and/or big computation, while neglecting the valuable chemical prior knowledge dwelling in chemists' minds. In this paper, we introduce an Electrochemistry-Informed Neural Network (ECINN) by explicitly embedding electrochemistry priors including the Butler-Volmer (BV), Nernst and diffusion equations on the backbone of neural networks for multi-task discovery of electrochemistry parameters. We applied the ECINN to voltammetry experiments of F e 2 + / F e 3 + ${{\rm F}{{\rm e}}^{2+}/{\rm F}{{\rm e}}^{3+}}$ and R u N H 3 6 2 + / R u N H 3 6 3 + ${{\rm R}{\rm u}{\left({\rm N}{{\rm H}}_{3}\right)}_{6}^{2+{\rm \ }}/{\rm R}{\rm u}{\left({\rm N}{{\rm H}}_{3}\right)}_{6}^{3+{\rm \ }}}$ redox couples to discover electrode kinetics and mass transport parameters. Notably, ECINN seamlessly integrated mass transport with BV to analyze the entire voltammogram to infer transfer coefficients directly, so offering a new approach to Tafel analysis by outdating various mass transport correction methods. In addition, ECINN can help discover the nature of electron transfer and is shown to refute incorrect physics if imposed. This work encourages chemists to embed their domain knowledge into machine learning models to start a new paradigm of chemistry-informed machine learning for better accountability, interpretability, and generalization.

Understanding Comorbidity Between Non-Suicidal Self-Injury and Depressive Symptoms in a Clinical Sample of Adolescents: A Network Analysis.

Background: Non-suicidal self-injury (NSSI) and depression often co-occur among adolescents with more severe clinical symptoms. This study examined the network structures of NSSI and depressive symptoms in adolescents. Methods: Participants were recruited in the psychiatric outpatient clinics of three tertiary hospitals between April 10 and July 10, 2023. All participants been already found with self-injury behaviors in outpatient when enrolled. NSSI diagnostic criteria and Patient Health Questionnaire-9 (PHQ-9) were utilized to collect NSSI and depressive symptoms separately. We performed a network analysis to visualize the correlation between each symptom and to identify core and bridging symptoms in comorbidities. Results: A total of 248 patients were enrolled in the study, with a mean age of 15.48 (SD = 1.62). Based on the PHQ-9 scores and grades, our results showed that the incidence of depression in adolescents with non-suicidal self-injury behavior was relatively high (N=235, 94.76%), with the majority having severe depression. The network analysis revealed that nodes D-6 "feeling bad, failing or letting yourself or your family down", D-1 "little interest or pleasure" and D-4 "feeling tired" were the most vital and most central symptoms. The most crucial bridging symptom is the node NSSI-8 "frequent thinking about self-injury", which connects the NSSI to the depression comorbid network. Conclusion: This study offers a significant symptom-level conceptualization of the association between NSSI and depressive symptoms in a clinical sample of adolescents, which not only enhances our understanding of the comorbid but also identifies potential treatment targets to prevent and treat comorbidity between adolescent NSSI and depression.

Association between PM2.5 and hypertension among the floating population in China: a cross-sectional study.

Few studies have investigated the association between PM2.5 and hypertension among floating populations. We therefore examined the relationship using binary logistic regression. Each grade of increment in the annual average PM2.5 (grade one: ≤15 µg/m3; grade two: 15-25 µg/m3; grade three: 25-35 µg/m3 [Excluding 25]; grade four: ≥35 µg/m3) was associated with an increased risk of hypertension (odds ratio [OR] = 1.081, 95% confidence interval (CI): 1.034-1.129). Among the female floating population (OR = 1.114, 95% CI: 1.030-1.204), those with education level of primary school and below (OR = 1.140, 95% CI: 1.058-1.229), construction workers (OR = 1.228, 95% CI: 1.058-1.426), and those living in the eastern region of China (OR = 1.241, 95% CI: 1.145-1.346) were more vulnerable to PM2.5. These results indicate that PM2.5 is positively associated with hypertension in floating populations. Floating populations who are female, less educated, construction workers, and living in the eastern region of China are more vulnerable to the adverse impacts of PM2.5.

Associations between short-term exposure to ambient PM2.5 and incident cases of cardiovascular disease in Yantai, China.

There are limited studies investigating the association between short-term exposure to PM2.5 and incident cardiovascular disease (CVD) cases in China. This study aims to examine the short-term effects of PM2.5 on the incidence of cardiovascular diseases. A combination of Poisson-distribution generalized linear model and distributed lag non-linear model was used to examine the association between short-term exposure to PM2.5 and incident cases of CVD. The results revealed that per 10 µg/m3 increment of PM2.5 would increase the incident CVD cases by 0.147% (Relative Risk: 1.00147, 95% Confidence Interval: 1.00008-1.00286) at a lag of 2 days. The stratified analyses showed higher effects risk in females, older residents (aged 60-75 years), and acute myocardial infarction group (p-value for difference <0.05). This study indicates that short-term exposure to PM2.5 may increase the risk of CVD and highlights the necessity for a higher air quality standard in Yantai, China.

Can uric acid affect the immune microenvironment in bladder cancer? A single-center multi-omics study.

Metabolic abnormalities are one of the important factors in bladder cancer (BCa) progression and microenvironmental disturbance. As an important product of purine metabolism, uric acid's (UA) role in BCa metabolism and immunotherapy remains unclear. In this study, we conducted a retrospective analysis of a cohort comprising 39 BCa patients treated with PD-1 and 169 patients who underwent radical cystectomy at Shanghai Tenth People's Hospital. Kaplan-Meier curves and Cox regression analysis showed that the prognosis of patients with high UA is worse (p = 0.007), and high UA is an independent risk factor for cancer specific survival in patients with BCa (p = 0.025). We established a hyperuricemia mouse model with BCa subcutaneous xenografts in vivo. The results revealed that the subcutaneous tumors of hyperuricemia mice had a greater weight and volume in comparison with the control group. Through flow cytometric analysis, the proportion of CD8+ and CD4+ T cells in these subcutaneous tumors was seen to decline significantly. We also evaluated the relationship of UA and BCa by muti-omic analysis. UA related genes were significantly increased in the CD8+ T cell of non-responders to immunotherapy by single-cell sequencing. An 11-gene UA related signature was constructed and the risk score negatively correlated with various immune cells and immune checkpoints. Finally, a nomogram was established using a UA related signature to forecast the survival rate of patients with BCa. Collectively, this study demonstrated that UA was an independent prognostic biomarker for BCa and was associated with worse immunotherapy response.

Electroacupuncture ameliorates cognitive impairment in APP/PS1 mouse by modulating TFEB levels to relieve ALP dysfunction.

Recently, the underlying mechanisms of acupuncture on the effects of Alzheimer's disease (AD) treatment have not been fully elucidated. Defects in ALP (autophagy-lysosomal pathway) and TFEB (transcription factor EB) play critical roles in AD. Our previous studies have demonstrated that electroacupuncture (EA) can ameliorate both ß-amyloid (Aß) pathology and cognitive function in APP/PS1 mice. However, the effects of EA on the expression of ALP and TFEB and their potential mechanisms require further investigation. Twenty-eight male APP/PS1 mice were randomly divided into Tg and Tg + EA groups, and 14 C57BL/6 mice served as the wild-type (WT) group. After 1 week of adaptation to the living environment, mice in the Tg + EA group were restrained in mouse bags and received manual acupuncture at Baihui (GV20) acupoint and EA stimulation at bilateral Yongquan (KI1) acupoints, using the same restraint method for WT and Tg groups. The intervention was applied for 15 min each time, every other day, lasting for six weeks. After intervention, the spatial learning and memory of the mice was assessed using the Morris water maze test. Hippocampal Aß expression was detected by immunohistochemistry and ELISA. Transmission electron microscopy (TEM) was used to observe autophagic vacuoles and autolysosomes in the hippocampus. Immunofluorescence method was applied to examine the expression of TFEB in CA1 region of the hippocampus and the co-localization of CTSD or LAMP1 with Aß. Western blot analysis was performed to evaluate the changes of LC3, p62, CTSD, LAMP1, TFEB and n-TFEB (nuclear TFEB) in the hippocampus. The findings of behavioral assessment indicated that EA alleviated the cognitive impairment of APP/PS1 mice. Compared with the WT group, the Tg group showed significant cognitive decline and abnormalities in ALP and TFEB function (P < 0.01 or P < 0.05). However, these abnormal changes were alleviated in the Tg + EA group (P < 0.01 or P < 0.05). The Tg group also showed more senile plaques and ALP dysfunction features, compared with the WT group, and these changes were alleviated by EA. In conclusion, this study highlights that EA ameliorated Aß pathology-related cognitive impairments in the APP/PS1 model associated with ALP and TFEB dysfunction.

A Lysosome-Targeted Magnetic Nanotorquer Mechanically Triggers Ferroptosis for Breast Cancer Treatment.

Targeting ferroptosis has attracted exponential attention to eradicate cancer cells with high iron-dependent growth. Increasing the level of intracellular labile iron pool via small molecules and iron-containing nanomaterials is an effective approach to induce ferroptosis but often faces insufficient efficacy due to the fast drug metabolism and toxicity issues on normal tissues. Therefore, developing a long-acting and selective approach to regulate ferroptosis is highly demanded in cancer treatment. Herein, a lysosome-targeted magnetic nanotorquer (T7-MNT) is proposed as the mechanical tool to dynamically induce the endogenous Fe2+ pool outbreak for ferroptosis of breast cancer. T7-MNTs target lysosomes via the transferrin receptor-mediated endocytosis in breast cancer cells. Under the programmed rotating magnetic field, T7-MNTs generate torques to trigger endogenous Fe2+ release by disrupting the lysosomal membrane. This magneto-mechanical manipulation can induce oxidative damage and antioxidant defense imbalance to boost frequency- and time-dependent lipid peroxidization. Importantly, in vivo studies show that T7-MNTs can efficiently trigger ferroptosis under the magnetic field and play as a long-acting physical inducer to boost ferrotherapy efficacy in combination with RSL3. It is anticipated that this dynamic targeted strategy can be coupled with current ferroptosis inducers to achieve enhanced efficacy and inspire the design of mechanical-based ferroptosis inducers for cancer treatment.

Hypoxia is correlated with the tumor immune microenvironment: Potential application of immunotherapy in bladder cancer.

OBJECTIVE: Hypoxia, which can considerably affect the tumor microenvironment, hinders the use of immunotherapy in bladder cancer (BLCA). Therefore, we aimed to identify reliable hypoxia-related biomarkers to guide clinical immunotherapy in BLCA. METHODS: Using data downloaded from TCGA-BLCA cohort, we determined BLCA subtypes which divide 408 samples into different subtypes. Tumor immune infiltration levels of two clusters were quantified using ssGSEA, MCPcounter, EPIC, ESTIMATE, and TIMER algorithms. Next, we constructed a hypoxia score based on the expression of hypoxia-related genes. The IMvigor210 cohort and SubMap analysis were used to predict immunotherapeutic responses in patients with different hypoxia scores. Hub genes were screened using cytoscape, immunohistochemistry (IHC), and multispectral immunofluorescence were used to detect the spatial distribution of immune markers. RESULTS: Patients with BLCA were categorized into cluster1 (n = 227) and Cluster2 (n = 181). Immune infiltration and expression of immune markers were higher in Cluster1. Immune infiltration was also more obvious in the high-hypoxia score group which related to a better predicted response to immunotherapy. IHC, and multispectral immunofluorescence confirmed the importance of TLR8 in immune infiltration and immune phenotype. CONCLUSIONS: BLCA subtype can evaluate the infiltration of immune cells in the tumor microenvironment of different patients. Hypoxia score in this study could effectively predict immunotherapeutic responses in patients with BLCA. TLR8 may be a potential target for clinical immunotherapy.

Prostate cancer-derived small extracellular vesicle proteins: the hope in diagnosis, prognosis, and therapeutics.

Current diagnostic tools for prostate cancer (PCa) diagnosis and risk stratification are insufficient. The hidden onset and poor efficacy of traditional therapies against metastatic PCa make this disease a heavy burden in global men's health. Prostate cancer-derived extracellular vesicles (PCDEVs) have garnered attention in recent years due to their important role in communications in tumor microenvironment. Recent advancements have demonstrated PCDEVs proteins play an important role in PCa invasion, progression, metastasis, therapeutic resistance, and immune escape. In this review, we briefly discuss the applications of sEV proteins in PCa diagnosis and prognosis in liquid biopsy, focus on the roles of the PCa-derived small EVs (sEVs) proteins in tumor microenvironment associated with cancer progression, and explore the therapeutic potential of sEV proteins applied for future metastatic PCa therapy.