Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma.

BACKGROUND: Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects. RESULTS: Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them. CONCLUSION: The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.

Adaptations to Optimized Interval Training in Soccer Players: A Comparative Analysis of Standardized Methods for Individualizing Interval Interventions.

Accurately prescribing supramaximal interval training facilitates targeting desired physiological adaptations. This study compared the homogeneity of adaptations in cardiorespiratory parameters to supramaximal [i.e., intensities beyond maximal aerobic speed (MAS)] interval interventions prescribed using anaerobic speed reserve (ASR), the speed attained at the end of 30-15 Intermittent Fitness Test (VIFT), and MAS. Using repeated-measures factorial design, and during the off-season phase of the athletes' yearly training cycle, thirty national-level soccer players (age = 19 ± 1.6 years; body mass = 78.9 ± 1.6 kg; height = 179 ± 4.7 cm; Body fat = 11 ± 0.9%) were randomized to interventions consisting of 2 sets of 6, 7, 8, 7, 8, and 9-min intervals (from 1st to 6th week), including 15 s running at Δ%20ASR (MAS + 0.2 × ASR), 120%MAS, or 95%VIFT followed by 15 s passive recovery. All ASR, VIFT, and MAS programs sufficiently stimulated adaptive mechanisms, improving relative maximal oxygen uptake [V̇O2max (p < 0.05; ES = 1.6, 1.2, and 1.1, respectively)], absolute V̇O2max (p < 0.05; ES = 1.5, 1.1, and 0.7), ventilation [V̇E (p < 0.05; ES = 1.6, 1.1, and 1.1)], O2 pulse [V̇O2/HR (p < 0.05; ES = 1.4, 1.1, and 0.6)], first and second ventilatory threshold [VT1 (p < 0.05; ES = 0.7, 0.8, and 0.7) and VT2 (p < 0.05; ES = 1.1, 1.1, and 0.8)], cardiac output [Q̇max (p = 1.5, 1.0, and 0.7)], and stroke volume [SVmax (p < 0.05; ES = 0.9, 0.7, and 0.5)]. Although there was no between-group difference for the change in the abovementioned variables over time, supramaximal interval training prescribed using ASR and VIFT resulted in a lower coefficient of variation [CV (inter-individual variability)] in physiological adaptations compared to exercise intensity determined as a proportion of MAS. Expressing the intensity of supramaximal interval programs according to the athlete's ASR and VIFT would assist in accurately prescribing interventions and facilitate imposing mechanical and related physiological stimulus according to the athletes' physiological ceiling. Such an approach leads to identical stimulation across athletes with differing profiles and potentially facilitates more homogenized adaptations.

Serum miR-22 is a novel prognostic marker for acute myeloid leukemia.

BACKGROUND: It has been demonstrated that aberrant expression of serum microRNAs is potential markers for the prognostic prediction of acute myeloid leukemia (AML). However, the clinical significance of serum miR-22 remained uncovered. In this study, we aimed to explore the potential prognostic value of serum miR-22 for AML. METHODS: Blood samples were collected from 124 patients with AML and 60 healthy individuals. Serum miR-22 level was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and its potential clinical value was investigated. RESULTS: Our results showed that serum miR-22 expression was significantly downregulated in AML subjects compared to healthy controls. Serum miR-22 levels were lowest in AML patients with M4/M5 subtypes, and low serum miR-22 expression occurred more frequently in AML patients with higher white blood cell counts or poor cytogenetic risk. Receiver operating characteristic (ROC) analysis revealed that serum miR-22 well differentiated AML cases from healthy controls. In addition, serum miR-22 downregulation was closely associated with worse clinical features and shorter survival. Low serum miR-22 expression was confirmed to be an independent predictor for overall survival and relapse-free survival in AML patients. Moreover, the expression level of serum miR-22 was dramatically increased following treatment. In addition, serum miR-22 levels were significantly higher in AML patients achieving complete remission (CR) than those without CR. CONCLUSION: Collectively, serum miR-22 might serve as a novel and promising prognostic biomarker for AML.

Global and Regional Burden and Trend of Neoplasms Attributable to Alcohol Consumption in the Past 3 Decades.

OBJECTIVES: To provide valuable insights for targeted cancer screening among high-risk patients, we analyzed the global and regional burden of neoplasms resulting from alcohol consumption between 1990 and 2019. METHODS: The information used in this study was collected from the Global Burden of Disease 2019 dataset. Initially, the database was used to extract details of mortality rates, disability-adjusted life years (DALYs), and the number of individuals affected by alcohol-related neoplasms (ARNs). Subsequently, the data were compared by cancer type, sex, age, region, and sociodemographic index. Furthermore, the study involved the calculation and comparison of estimated annual percentage changes in age-standardized DALYs rates (ASDRs) and mortality rates. RESULTS: The impact of alcohol on the burden of cancer varied by type of cancer, sex, age, and geographical location. Notably, males exhibited significantly higher ASDRs compared with females. Specifically, in 2019, alcohol emerged as the primary contributor to the number of DALYs associated with esophageal cancer, followed by liver cancer and colorectal cancer in men. Patients aged 50+ years exhibited a heightened rate of DALYs associated with ARNs. From 1990 to 2019, ASDRs among individuals with ARNs did not exhibit a decline in low-middle and low sociodemographic index regions. CONCLUSIONS: Alcohol consumption represents a significant risk factor for the burden of cancer, particularly within the realm of digestive system malignancies. Consequently, targeted cancer screening efforts should be directed toward the population that engages in alcohol drinking, with a particular focus on men aged 50 years and older, residing in economically disadvantaged areas.