The tumor microenvironment (TME), which includes acidic and hypoxic conditions, severely impedes the therapeutic efficacy of antitumor agents. Herein, MnO2‐loaded, bovine serum albumin, and PEG ...co‐modified mesoporous CaSiO3 nanoparticles (CaM‐PB NPs) are developed as a nanoplatform with sequential theranostic functions for the engineering of TME. The MnO2 NPs generate O2 in situ by reacting with endogenous H2O2, relieving the hypoxic state of the TME that further modulates the cancer cell cycle status to S phase, which improves the potency of co‐loaded S phase‐sensitive chemotherapeutic drugs. After the hypoxia relief, CaM‐PB can sustainably release drugs due to the enlarged pores of mesoporous CaSiO3 in the acidic TME, preventing the drug pre‐leakage into the blood circulation and insufficient drug accumulation at tumor sites. Moreover, the Mn2+ released from the MnO2 NPs at tumor sites can potentially serve as a diagnostic agent, enabling the identification of tumor regions by T1‐weighted magnetic resonance imaging during therapy. In vivo pharmacodynamics results demonstrate that these synergetic effects caused by CaM‐PB NPs significantly contribute to the inhibition of tumor progression. Therefore, the CaM‐PB NPs with sequential theranostic functions are a promising system for effective cancer therapy.
An MnO2‐loaded, poly(ethylene glycol) and bovine serum albumin co‐modified mesoporous CaSiO3 nanoparticle (CaM‐PB) is developed for the engineering of the tumor microenvironment (TME). CaM‐PB can sequentially relieve the hypoxic state of the TME, tune cancer cell cycle to S phase, and sustainably release S phase‐sensitive drugs for improved cancer therapy, simultaneously providing a TME‐responsive magnetic resonance imaging for real‐time monitoring.
The question of whether spatial attention can modulate initial afferent activity in area V1, as measured by the earliest visual event‐related potential (ERP) component “C1”, is still the subject of ...debate. Because attention always enhances behavioral performance, previous research has focused on finding evidence of attention‐related enhancements in visual neural responses. However, recent psychophysical studies revealed a complex picture of attention's influence on visual perception: attention amplifies the perceived contrast of low‐contrast stimuli while dampening the perceived contrast of high‐contrast stimuli. This evidence suggests that attention may not invariably augment visual neural responses but could instead exert inhibitory effects under certain circumstances. Whether this bi‐directional modulation of attention also manifests in C1 and whether the modulation of C1 underpins the attentional influence on contrast perception remain unknown. To address these questions, we conducted two experiments (N = 67 in total) by employing a combination of behavioral and ERP methodologies. Our results did not unveil a uniform attentional enhancement or attenuation effect of C1 across all subjects. However, an intriguing correlation between the attentional effects of C1 and contrast appearance for high‐contrast stimuli did emerge, revealing an association between attentional modulation of C1 and the attentional modulation of contrast appearance. This finding offers new insights into the relationship between attention, perceptual experience, and early visual neural processing, suggesting that the attentional effect on subjective visual perception could be mediated by the attentional modulation of the earliest visual cortical response.
Our findings reveal a positive correlation between attentional modulations on the C1 component and subjective contrast perception. Although the averaged C1 attention effect across participants did not reach statistical significance, our finding implies that the attentional modulation of neural responses in V1 may contribute to the attention effect on visual perception.
Advanced oxidation processes offer effective solutions in treating wastewater from various industries. This study is the first time to investigate the potential of carbonate-activated hydrogen ...peroxide (CAP) oxidation process for the removal of organic pollutant from highly alkaline wastewaters. Azo dye acid orange 7 (AO7) was selected as a model pollutant. The influences of various parameters on AO7 decolorization by the CAP oxidation were evaluated. Furthermore, the active species involved in AO7 degradation were explored using scavenger experiments and electron spin resonance analysis. Additionally, AO7 degradation products by the CAP oxidation were identified to elucidate possible transformation pathways. Results showed that the CAP oxidation had better AO7 decolorization performance compared to bicarbonate-activated hydrogen peroxide method. The AO7 decolorization efficiency augmented from 3.70 ± 0.76% to 54.27 ± 2.65% when carbonate concentration was increased from 0 to 50 mM at pH 13.0, and then changed slightly with further increasing carbonate concentration to 70 mM. It increased almost linearly from 5.95 ± 0.32% to 94.03 ± 0.39% as H2O2 concentration was increased from 5 to 50 mM. Moreover, trace amount of Co(II) could facilitate AO7 decolorization by the CAP reaction. Superoxide and carbonate radicals might be the main reactive oxygen species involved in the CAP process. Finally, a possible degradation pathway of AO7 by the CAP oxidation was proposed based on the identified products.
•Carbonate-activated H2O2 oxidation was successfully applied for azo dye removal.•Carbonate and H2O2 concentration positively affected CAP for AO7 removal.•O2. and CO3 might be the main ROSs in the CAP oxidation process•A possible degradation pathway of AO7 by the CAP oxidation were proposed.
Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis, and the androgen receptor regulates prostate cancer (PCa) progression. It is unclear whether the androgen ...receptor regulates the recruitment of prostate cancer cells to the bone microenvironment, even bone metastases, through exosomes. Here, we found that exosomes isolated from PCa cells after knocking down androgen receptor (AR) or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts. In addition, AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase (circ-DHPS) in PCa cells, which can be transported to osteoblasts by exosomes. Circ-DHPS acts as a competitive endogenous RNA (ceRNA) against endogenous miR-214-3p to promote C-C chemokine ligand 5 (CCL5) levels in osteoblasts. Increasing the level of CCL5 in osteoblasts could recruit more PCa cells into the bone microenvironment. Thus, blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.
Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and ...select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients.
We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes.
CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2-92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4-18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival.
This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments.
ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019.
The carotenoids, including lycopene, lutein, astaxanthin, and zeaxanthin belong to the isoprenoids, whose basic structure is made up of eight isoprene units, resulting in a C40 backbone, though some ...of them are only trace components in Euglena. They are essential to all photosynthetic organisms due to their superior photoprotective and antioxidant properties. Their dietary functions decrease the risk of breast, cervical, vaginal, and colorectal cancers and cardiovascular and eye diseases. Antioxidant functions of carotenoids are based on mechanisms such as quenching free radicals, mitigating damage from reactive oxidant species, and hindering lipid peroxidation. With the development of carotenoid studies, their distribution, functions, and composition have been identified in microalgae and higher plants. Although bleached or achlorophyllous mutants of Euglena were among the earliest carotenoid-related microalgae under investigation, current knowledge on the composition and biosynthesis of these compounds in Euglena is still elusive. This review aims to overview what is known about carotenoid metabolism in Euglena, focusing on the carotenoid distribution and structure, biosynthesis pathway, and accumulation in Euglena strains and mutants under environmental stresses and different culture conditions. Moreover, we also summarize the potential applications in therapy preventing carcinogenesis, cosmetic industries, food industries, and animal feed.
Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to ...immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer.
This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT).
Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response.
This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.
Two-dimensional photocatalysts with full optical absorption have attracted widespread attention for water splitting and pollutant degradation, but only few single materials can meet this criterion. ...In the present work, for the first time, we theoretically constructed an In2Se3/MoS2 heterostructure composite and disclosed its outstanding oxidation ability for catalysis. The results revealed that the In2Se3/MoS2 composite comprised van der Waals heterojunctions. With the binding energy of 0.315 J m−2, the heterostructure was thermodynamically stable. An indirect band gap of 0.88 eV was obtained, which was smaller than that of the monolayer. Facilitated by the type-II heterostructure, there was migration of photoinduced electrons from MoS2 to the In2Se3 monolayer, promoting the separation of charge carriers. Moreover, the mobility of the charge carriers in the composite was excellent because of their small effective mass and the outstanding optical absorption of infrared, visible and ultraviolet light. It was found that the electronic and optical properties were strain-tunable. Specifically, under a strain of 4%, the composite band changed from p-type to n-type, and the light absorption further broadened to the near-infrared region. Certain aspects of the theoretical findings were observed experimentally. It is envisioned that In2Se3/MoS2 is a potential photoelectric material for experimental research in the area of photocatalysis.
Background
Metabolic syndrome (MetS) was a risk factor for papillary thyroid cancer (PTC). Whether MetS impacts the aggressiveness of PTC is still unclear. We carried out this study to clarify this ...issue.
Methods
We evaluated 745 consecutive PTC patients treated with surgery. Patients were divided into three groups based on their number of MetS components: patients without any MetS components, patients with 1–2 MetS components, and patients with 3–5 MetS components. The clinical features and histological aggressiveness of PTC at the time of diagnosis were evaluated.
Results
A total of 745 patients were included in this study. And, 145 patients had three or more metabolic components and were diagnosed as MetS. MetS was a risk factor for larger tumors (OR = 2.29, 95% CI: 1.31–4.03), more lymph node metastasis (OR = 1.97, 95% CI: 1.11–3.51), and later clinical stage (OR = 7.92, 95% CI: 1.59–39.34) after correction for age, sex, and thyroid-stimulating hormone (TSH) level and body mass index (BMI).
Conclusion
In our hospital-based cohort study MetS was associated with the aggressiveness of PTC. This association was still significant after adjusting for age, sex, TSH, and BMI.
Using quantum walks (QWs) to rank the centrality of nodes in networks, represented by graphs, is advantageous compared to certain widely used classical algorithms. However, it is challenging to ...implement a directed graph via QW, since it corresponds to a non-Hermitian Hamiltonian and thus cannot be accomplished by conventional QW. Here we report the realizations of centrality rankings of a three-, a four-, and a nine-vertex directed graph with parity-time (PT) symmetric quantum walks by using high-dimensional photonic quantum states, multiple concatenated interferometers, and dimension dependent loss to achieve these. We demonstrate the advantage of the QW approach experimentally by breaking the vertex rank degeneracy in a four-vertex graph. Furthermore, we extend our experiment from single-photon to two-photon Fock states as inputs and realize the centrality ranking of a nine-vertex graph. Our work shows that a PT symmetric multiphoton quantum walk paves the way for realizing advanced algorithms.
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