Abstract Nuclear-targeted therapy by delivering anticancer drug directly into cancer cell nuclei can elicit synergistic therapeutic effects and kill these cancer cells with much enhanced ...efficiencies. Besides nuclear targeting, another difficulty in nuclear-targeted therapy is how to achieve real-time monitoring of the therapy process simultaneously. In this article we report on the development of multifunctional upconversion nanoparticles (UCNPs) which were able to target cancer cell nuclei, and thus deliver the anticancer drug directly to the nuclear region and simultaneously image cell nucleus by magnetic resonance (MR)/upconversion fluorescent for real-time guidance of their therapeutic action simultaneously. The Er/Yb-doped NaYF4 core and NaGdF4 shell endow the core/shell structured UCNPs with enhanced upconversion fluorescent imaging and more sensitive T1 -MR imaging performances, and the surface conjugation of TAT peptide served as a key role in the nuclear targeting and nuclear transport process. This multifunctional UCNPs-based nano-theranostic was used to improve the efficacy of DOX in Hela humor tumor models, by direct DOX delivery to the nucleus under the synchronous monitoring of the nano-theranostics. Further development of this technology may provide more exciting opportunities in treating cancer disease by nuclear-targeted therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Neoadjuvant radiochemotherapy (nRCT) followed by surgery has become the gold standard treatment in patients with locally advanced esophageal cancer. The pathological response is an important ...predictor in such patients. This work represents a single-center analysis investigating the impact of pathological complete response (pCR) on treatment outcome.
All patients treated with nRCT followed by surgery between January 2005 and December 2015 were reviewed. The patients were categorized into two groups according to the pathological response following nRCT: pCR group and non-pCR group.
Fifty-six patients with invasive cancer, 23 patients (41.1%) achieved pCR and 33 patients had non-pCR (58.9%) following nRCT. The average age was 62 years (±9.1), and most patients were males (83.9%). Histological types included squamous cell carcinoma (75%) and adenocarcinoma (25%). The total radiation dose was 45 Gy in 76.8% of the patients and 50.4 Gy in 23.2%. The median overall survival (OS) of the entire group was 3.5±1.2 years, and the 5-year OS rate was 38.2%, while the median disease-free survival (DFS) was 2.1±0.4 years and the 5-year DFS rate was 33.1%. The patients who achieved pCR had significantly higher 5-year OS and 5-year DFS rates: 47.2% and 48% compared to 27.3% and 21% for the non-pCR patients respectively (P=0.04, 0.03). The median time of local recurrence was 3.8±0.4 years in pCR group and 1.8±0.2 years in non-pCR group (P=0.01), while the median time of distant metastases in pCR group was 1.2±0.5 years and 1.1±0.2 years in non-pCR group (P=0.6).
Complete pathological response predicts significantly higher rates of OS and DFS in patients with locally advanced esophageal cancer treated with nRCT followed by surgery.
To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the ...appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients.
A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node.
All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location.
In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
To compare three-dimensional (3D) and four-dimensional (4D) computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in ...terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing.
The IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing.
Compared with IMRT, median lung volumes exposed to 5, 10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%, 5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%, 5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index CI, 1.99) and greater irradiation of the heart (heart-V40, 41.8%) compared with the IMRT plan(CI, 1.55, heart-V40, 35.7%) or the three-beam proton plan (CI, 1.46, heart-V40, 27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas filling.
Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
In Internet of Things (IoT) networks, the amount of data sensed by user devices may be huge, resulting in the serious network congestion. To solve this problem, intelligent data compression is ...critical. The variational information bottleneck (VIB) approach, combined with machine learning, can be employed to train the encoder and decoder, so that the required transmission data size can be reduced significantly. However, VIB suffers from the computing burden and network insecurity. In this letter, we propose a blockchain-enabled VIB (BVIB) approach to relieve the computing burden while guaranteeing network security. Extensive simulations conducted by Python and C++ demonstrate that BVIB outperforms VIB by 36%, 22% and 57% in terms of time and CPU cycles cost, mutual information, and accuracy under attack, respectively.
Hydroxyapatite (HAp), as the main inorganic constituent in vertebrate bones, is an important biomaterial. However, fabricating biomimetic HAp ordered arrays of one-dimensional nanostructures remains ...a challenge. Herein, we report a solvothermal method for the preparation of HAp nanowire/nanotube ordered arrays with biomimetic structures using CaCl2 and NaH2PO4middle dotH2O in ternary solvents of water, ethylene glycol (EG) and N,N-dimethylformamide (DMF) without using any surfactant. The effects of the solvents on the morphology and crystal phase of the product as well as the formation mechanism of HAp nanowire/nanotube ordered arrays are investigated. This method does not need any hard template or surfactant, avoiding the procedures and cost for their removal in the product. The products are characterized with X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetric analysis (DSC) and thermogravimetric analysis (TG). The cytotoxicity of the as-prepared HAp samples with different morphologies are also tested.
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Recent studies have revealed that interactions between pathogenic microorganisms, which have a tendency to parasitize the ...skin of AD patients, play a significant role in the progression of the disease. Furthermore, specific species of commensal bacteria in the human intestinal tract can have a profound impact on the immune system by promoting inflammation and pruritogenesis in AD, while also regulating adaptive immunity. Natural products (NPs) have emerged as promising agents for the treatment of various diseases. Consequently, there is growing interest in utilizing natural products as a novel therapeutic approach for managing AD, with a focus on modulating both skin and gut microbiota. In this review, we discuss the mechanisms and interplay between the skin and gut microbiota in relation to AD. Additionally, we provide a comprehensive overview of recent clinical and fundamental research on NPs targeting the skin and gut microbiota for AD treatment. We anticipate that our work will contribute to the future development of NPs and facilitate research on microbial mechanisms, based on the efficacy of NPs in treating AD.
Under the action of natural products, microorganisms participate in a complete cycle of the "gut-brain-skin" axis linkage mechanism, thereby regulating the development of atopic dermatitis.
The northern high latitude (NHL, 40°N to 90°N) is where the second peak region of gross primary productivity (GPP) other than the tropics. The summer NHL GPP is about 80% of the tropical peak, but ...both regions are still highly uncertain (Norton et al. 2019, https://doi.org/10.5194/bg-16-3069-2019). Carbonyl sulfide (OCS) provides an important proxy for photosynthetic carbon uptake. Here we optimize the OCS plant uptake fluxes across the NHL by fitting atmospheric concentration simulation with the GEOS‐CHEM global transport model to the aircraft profiles acquired over Alaska during NASA's Carbon in Arctic Reservoirs Vulnerability Experiment (2012–2015). We use the empirical biome‐specific linear relationship between OCS plant uptake flux and GPP to derive the six plant uptake OCS fluxes from different GPP data. Such GPP‐based fluxes are used to drive the concentration simulations. We evaluate the simulations against the independent observations at two ground sites of Alaska. The optimized OCS fluxes suggest the NHL plant uptake OCS flux of −247 Gg S year−1, about 25% stronger than the ensemble mean of the six GPP‐based OCS fluxes. GPP‐based OCS fluxes systematically underestimate the peak growing season across the NHL, while a subset of models predict early start of season in Alaska, consistent with previous studies of net ecosystem exchange. The OCS optimized GPP of 34 PgC yr−1 for NHL is also about 25% more than the ensembles mean from six GPP data. Further work is needed to fully understand the environmental and biotic drivers and quantify their rate of photosynthetic carbon uptake in Arctic ecosystems.
Key Points
Carbonyl sulfide is shown an useful proxy to constrain gross primary productivity in regional and global scales
This study used Carbon in Arctic Reservoirs Vulnerability Experiment observations and GEOSCHEM modeling of carbonyl sulfide to benchmark the multi‐model gross primary productivity at norther high latitude
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This prospective phase 2 study evaluated the efficacy and safety of intensity modulated radiation therapy plus etoposide/cisplatin (EP) for patients with unresectable thymic epithelial tumors (TETs).
...Patients with limited advanced unresectable TETs whose lesions could be encompassed within radiation fields were enrolled in this study. Two cycles of EP (75 mg/m2 etoposide and 25 mg/m2 cisplatin on days 1-3 and days 29-31) were administered concurrently with radiation therapy, followed by 2 cycles after radiation therapy. The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival rate, overall survival rate, and incidence of adverse events.
Fifty-six patients were enrolled between June 2011 and May 2018. Twenty-two and 34 patients had thymomas and thymic carcinomas, respectively. The median age was 52 (range, 21-76) years, and 30 patients (53.6%) were men. Eight patients (14.3%) had stage III tumors, 6 (10.7%) had stage IVA tumors, and 42 (75.0%) had stage IVB tumors. The objective response rate was 85.7% (95% confidence interval, 76.3%-95.2%). With a median follow-up of 46 (range, 7-101) months, the 1-, 2-, and 5-year progression-free survival rates were 66.1%, 48.0%, and 29.5%, and the 1-, 2-, and 5-year overall survival rates were 91.0%, 76.2%, and 56.2%, respectively. The most common grade 3 to 4 adverse event was leukopenia (42.9%). Pulmonary fibrosis was also observed (5.3%).
Because intensity modulated radiation therapy with EP is effective and safe for limited advanced unresectable TETs, it could be a suitable treatment option for such patients.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Previous data from our institution showed that hypofractionated thoracic radiotherapy (HypoTRT) with concurrent etoposide/platinum chemotherapy yielded favorable survival in patients with ...limited-stage small cell lung cancer (LS-SCLC). The present study retrospectively compared the survival outcomes, failure patterns and toxicities between groups of LS-SCLC patients treated with conventionally fractionated thoracic radiotherapy (ConvTRT) or HypoTRT combined with chemotherapy.
Medical records of LS-SCLC patients between January 2010 and December 2013 at Fudan University Shanghai Cancer Center were retrospectively reviewed. All patients treated with chemotherapy and ConvTRT (2 Gy per fraction daily, DT ≥ 56 Gy) or HypoTRT (2.5 Gy per fraction daily, DT = 55 Gy) were eligible for analysis. Progression-free survival (PFS) and overall survival (OS) were generated for different populations using the Kaplan-Meier method and compared using the log-rank test. Comparisons of failure patterns and toxicity were analyzed using the χ
test.
A total of 170 patients treated with HypoTRT (n = 69) or ConvTRT (n = 101) were eligible for analysis. The median PFS and OS were 13.7 and 25.3 months, respectively, in the ConvTRT cohort, which was similar to the HypoTRT cohort (PFS 18.2 months, p = 0.991, and OS 27.2 months, p = 0.698), with a median follow-up of 30 months. Multivariate analysis revealed that PCI and TNM stage were prognostic factors for PFS and that PCI was prognostic for OS. The patterns of failure (stratified by local-regional recurrence, distant metastasis or both as first relapse) were similar between the dose cohorts (p = 0.693, p = 0.330, p = 0.572). Distant metastasis remained the main failure pattern. The brain was the most frequent remote failure site, followed by bone, liver and adrenal gland. PCI improved the 2-year survival rate from 46.1% to 70.0% and the 2-year PFS rate from 20.9% to 45.3%, respectively (p < 0.001). Grade ≥3 esophagitis and pneumonitis occurred in 9.9% and 11.9%, respectively, of the patients in the ConvTRT cohort and in 11.6% and 10.0%, respectively, of those in the HypoTRT cohort (p = 0.815).
This retrospective analysis demonstrated that HypoTRT or ConvTRT combined with etoposide/platinum chemotherapy yielded statistically similar survival, treatment failure outcomes, and toxicity profiles. PCI correlated with improved PFS and OS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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