Evolving Tumor Characteristics and Smart Nanodrugs for Tumor Immunotherapy.

Typical physiological characteristics of tumors, such as weak acidity, low oxygen content, and upregulation of certain enzymes in the tumor microenvironment (TME), provide survival advantages when exposed to targeted attacks by drugs and responsive nanomedicines. Consequently, cancer treatment has significantly progressed in recent years. However, the evolution and adaptation of tumor characteristics still pose many challenges for current treatment methods. Therefore, efficient and precise cancer treatments require an understanding of the heterogeneity degree of various factors in cancer cells during tumor evolution to exploit the typical TME characteristics and manage the mutation process. The highly heterogeneous tumor and infiltrating stromal cells, immune cells, and extracellular components collectively form a unique TME, which plays a crucial role in tumor malignancy, including proliferation, invasion, metastasis, and immune escape. Therefore, the development of new treatment methods that can adapt to the evolutionary characteristics of tumors has become an intense focus in current cancer treatment research. This paper explores the latest understanding of cancer evolution, focusing on how tumors use new antigens to shape their "new faces"; how immune system cells, such as cytotoxic T cells, regulatory T cells, macrophages, and natural killer cells, help tumors become "invisible", that is, immune escape; whether the diverse cancer-associated fibroblasts provide support and coordination for tumors; and whether it is possible to attack tumors in reverse. This paper discusses the limitations of targeted therapy driven by tumor evolution factors and explores future strategies and the potential of intelligent nanomedicines, including the systematic coordination of tumor evolution factors and adaptive methods, to meet this therapeutic challenge.

Exosome-Transmitted miR-25 Induced by H. pylori Promotes Vascular Endothelial Cell Injury by Targeting KLF2.

Background: Increasing evidence has shown that Helicobacter pylori is associated with coronary heart disease (CHD); however, the underlying mechanism remains unclear. Methods: The expression of miR-25 and mRNAs was measured using qRT-PCR. Protein levels were detected using western blotting and exosomes were assessed with an electron microscope. The target gene of miR-25 was identified using the luciferase report system. Results:H. pylori infection increased the expression of miR-25 in gastric epithelial cells and was associated with increased levels of exosome-transmitted miR-25 in human peripheral blood. Mechanistic investigation showed the Kruppel-like factor 2 (KLF2) was a direct target of exosome-transmitted miR-25 in vascular endothelial cells. In addition, the miR-25/KLF2 axis regulated the NF-κB signaling pathway, resulting in increased expression of interleukin 6 (IL6), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). Conclusion: Our findings suggest that the miR-25/KLF2 axis may be a potential therapeutic target for H. pylori-associated CHD. Furthermore, high levels of exosome-transmitted miR-25 in peripheral blood may pose a potential risk for CHD.

Computed tomography-magnetic resonance imaging fusion-guided iodine-125 seed implantation for single malignant brain tumor: Feasibility and safety.

BACKGROUND: To investigate the feasibility and safety of computed tomography-magnetic resonance imaging (CT-MRI) fusion-guided iodine-125 seed implantation for a single malignant brain tumor. METHODS: From November 2015 to October 2016, 12 patients with a single malignant brain tumor were treated with permanent iodine-125 seeds implantation. CT-MRI fusion images were used to make the preoperative treatment plan, intraoperative dose optimization, postoperative verification, and tumor response follow-up. The dosimetry parameters of CT-MRI image fusion plans were compared between preprocedures and postprocedures, including plan target volume, V100 (the percentage of the target volume covered by the prescription dose [PD]), D90 (the dose that covers 90% of the target volume), and V200 (the percentage volume of the brain tumor receiving 200% of the PD). Adverse events were graded by the Common Terminology Criteria for Adverse Events. Clinical and radiological follow-ups were performed at a 3-month interval. RESULTS: All the interstitial implantations were completed successfully under the guidance of CT-MRI image fusion. The dosimetry parameters of CT-MRI image fusion postplans did not differ significantly from those of preplans (P > 0.05). No higher than Grade 2 adverse events were observed during the follow-up. Tumor control was achieved in 10 of 12 patients (83.33%). The median overall survival time was 15.05 ± 3.35 months (95% confidence interval 12.99-17.26). CONCLUSIONS: CT-MRI image fusion is feasible for the design, optimization, and verification of treatment planning. CT-MRI fusion-based brachytherapy may improve dosimetry of brain tumor while sparing the normal structures, potentially impacting disease control, treatment-related toxicity, and long-term survival.

[Cultivation of aerobic granular sludge with municipal wastewater and studies on its characteristics under the continuous flow].

The aerobic granular sludge was cultivated successfully in a continuous-flow airlift aerobic granular sludge fluidized bed (CAFB), with low-concentration municipal sewage as the influent and flocculent activated sludge as the seeding sludge. The formation, characteristics and the biological diversity of the aerobic granules in the CAFB were investigated and analyzed. Experimental results showed that many dense and compact granules with diameter of 800-1 000 microm were formed as early as the 6th days operation. At the start-up stage, sludge volume index (SVI) decreased to 35 mL x g(-1), the mixed liquor suspended solid (MLSS) concentration increased to 6000 mg x L(-1), and the mass fraction of extracellular polymeric substances increased significantly. The granules presented a good biological diversity and high biomass contents at the steady running stage. The aerobic granules were basically composed of coccid and bacillus as observed by the scanning electron microscope. A large number of voids and channels were found to be located on the surface of the granules. The removal rate of COD maintained at 70% -75% at the steady stage of CAFB running, and the effluent COD concentrations were 70 mg x L(-1). At the 32nd day of operation, filamentous bacteria grew apparently and sludge bulking happened. Above results showed the CAFB aerobic granules formed rapidly, and performed a good ability on the pollutant removal. However, more work is necessary on the steady running of this novel bioreactor in the future.

Down-regulation of ALKBH2 increases cisplatin sensitivity in H1299 lung cancer cells.

AIM: To elucidate the combined effect of alkylated DNA repair protein alkB homolog 2 (ALKBH2)-targeting gene therapy and cisplatin (cDDP) chemotherapy on the non-small cell lung cancer (NSCLC) H1299 cell line. METHODS: ALKBH2 was down-regulated in H1299 cells by lentivirus-mediated RNA interference (RNAi). Changes in ALKBH2 expression were determined using real-time RT-PCR and Western blotting. Cell viability was evaluated using MTT assay. DNA synthesis in proliferating cells was determined using BrdU incorporation assay. Cell apoptosis was determined using flow cytometry. RESULTS: Lentivirus-mediated ALKBH2 silencing alone did not induce apoptosis or attenuate the growth potential of H1299 cells within five days post-infection. Combined treatment modalities with lentivirus-mediated ALKBH2 down-regulation and cDDP (333 µmol/L) were significantly more potent in inhibiting cell growth and inducing apoptosis than mono-chemotherapy. CONCLUSION: Combined treatment modalities of ALKBH2 knockdown and cDDP chemotherapy have the potential to improve the efficacy in the treatment of NSCLC.

Light coupling and modulation in coupled nanowire ring-Fabry-Pérot cavity.

CdS nanowire (NW) ring cavities were fabricated and studied for the first time. The rings with radii from 2.1 to 5.9 microm were fabricated by a nanoprobe system installed in a scanning electron microscope. Radius dependent whispering gallery modes (WGMs) were observed. A straight CdS NW with Fabry-Pérot (F-P) cavity structure was fabricated and placed by the side of a NW ring cavity to form a coupled ring-F-P cavity. When the NW ring was excited by a focused laser, a bright green light spot was observed at the output end of the straight NW, indicating that the latter had served as an effect waveguide to couple the light out from the ring cavity. The corresponding light spectrum showed that the WGMs had been modulated. We confirmed that the NW F-P cavity had served as a modulator. Such a coupled cavity has potential application in a nanophotonic system.

[Method for concentration determination of mineral-oil fog in the air of workplace].

OBJECTIVE: To study the method of concentration determination of mineral-oil fog in the air of workplace. METHODS: Four filter films such as synthetic fabric filter film, beta glass fiber filter film, chronic filter paper and microporous film were used in this study. Two kinds of dust samplers were used to collect the sample, one sampling at fast flow rate in a short time and the other sampling at slow flow rate with long duration. Subsequently, the filter membrane was weighed with electronic analytical balance. According to sampling efficiency and incremental size, the adsorbent ability of four different filter membranes was compared. RESULTS: When the flow rate was between 10 approximately 20 L/min and the sampling time was between 10 approximately 15 min, the average sampling efficiency of synthetic fabric filter film was 95.61% and the increased weight ranged from 0.87 to 2.60 mg. When the flow rate was between 10 approximately 20 L/min and sampling time was between 10 approximately 15 min, the average sampling efficiency of beta glass fiber filter film was 97.57% and the increased weight was 0.75 approximately 2.47 mg. When the flow rate was between 5 approximately 10 L/min and the sampling time between 10 approximately 20 min, the average sampling efficiency of chronic filter paper and microporous film was 48.94% and 63.15%, respectively and the increased weight was 0.75 approximately 2.15 mg and 0.23 approximately 0.85 mg, respectively. When the flow rate was 3.5 L/min and the sampling time was between 100 approximately 166 min, the average sampling efficiency of filter film were 94.44% and 93.45%, respectively and the average increased weight was 1.28 mg for beta glass fiber filter film and 0.78 mg for beta glass fiber filter film and synthetic fabric synthetic fabric filter film. The average sampling efficiency of chronic filter paper and microporous film were 37.65% and 88.21%, respectively. The average increased weight was 4.30 mg and 1.23 mg, respectively. CONCLUSION: Sampling with synthetic fabric filter film and beta glass fiber filter film is credible, accurate, simple and feasible for determination of the concentration of mineral-oil fog in workplaces.