Functional 2D Iron-Based Nanosheets for Synergistic Immunotherapy, Phototherapy, and Chemotherapy of Tumor.

Immunotherapy efficacy has been limited by tumor-associated macrophages (TAMs), which are the most abundant immune regulatory cells infiltrating around tumor tissues. The repolarization of pro-tumor M2 TAMs to anti-tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron-based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as AP FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation-activated chemotherapy. A series of in vitro and in vivo results corroborate that AP FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.

A Comparison of Two Supplementary Doses of Vitamin A on Performance, Intestine and Immune Organ Development, as well as Gene Expression of Inflammatory Factors in Young Hy-Line Brown Laying Pullets.

The objective of this study was to compare two supplementary doses (6000 vs. 12,000 IU/kg) of vitamin A (VA) on the performance, development of intestine and immune organs, as well as gene expression of inflammatory factors in young Hy-Line Brown laying pullets. A total of 288 one-day-old Hy-Line Brown laying pullets (weighing 42.15 ± 0.23 g) were allotted into two treatments with 12 replicate cages and 12 birds per cage. During the 35-day period, the pullets were fed a basal diet supplemented with different doses of VA (6000 IU/kg VA in control group; 12,000 IU/kg VA in treatment group), respectively. The results showed that supplementary high doses of VA reduced the feed-to-gain ratio from day 21 to 35 (p < 0.05). Moreover, the pullets fed high doses of VA diets had increased length and relative weight of duodenum, jejunum, and ileum (p < 0.05). From observations on morphology, high doses of VA diets increased the villus height and the ratio of villus height to crypt depth in the jejunum and ileum (p < 0.05). High doses of VA diets also increased the relative weight of immune organs (p < 0.05). Furthermore, the gene expressions of inflammatory factors were decreased in the thymus of the pullets fed high doses of VA diets (p < 0.05). In summary, supplementary 12,000 IU/kg doses of VA improved performance and intestine and immune organ development, and alleviated gene expressions of inflammatory factors in young Hy-Line Brown laying pullets.

Exploring the clinical efficacy of a self-made acne prescription based on high-throughput sequencing.

BACKGROUND: We used high-throughput sequencing on skin microbial flora to assess the effectiveness of an acne prescription to formulate evidence for clinical decision-making. METHODS: We randomized 20 outpatients into two groups. The treatment group was given the acne formula orally. The control group took capsules of the Chinese patent medicine Qingre Anchuang. Both groups used a chloramphenicol tincture externally. After 14 days of treatment, we collected their skin samples and extracted the deoxyribonucleic acid for analysis. RESULTS: Forty samples were sequenced in this experiment, and of these, 1865 operational taxonomic units were obtained, belonging to 736 genera and 853 strains of 34 phyla. By alpha and beta diversity analysis, the abundance of microbial species in both the experimental and control groups before treatment was higher than after treatment, indicating the intervention drugs in this experiment had a bacteriostatic effect. Through the analysis of variance, we found that Subdoligranulum, Bifidobacterium, Bacteroides, and Akkermansia displayed large changes during the treatment. According to the linear discriminant analysis effect size, we discovered the bacteria groups with the greatest changes in the control group after treatment were Firmicutes, Clostridia, Proteobacteria, and Gammaproteobacteria. The flora of the experimental group before and after treatment were Corynebacteriaceae, Corynebacteriales, Cutibacterium, Propionibacteriales, Propionibacteriaceae, and Actinobacteria. CONCLUSION: The acne prescription had a reliable intervention effect on some epidermal microbial flora of patients with acne vulgaris and could inhibit the growth of acne-related microbial flora, such as Propionibacterium.

Inter-spacecraft offset frequency setting strategy in the Taiji program.

For controlling the beat frequency of heterodyne interferometry so that the Taiji program can detect gravitational waves in space, an offset frequency setting strategy based on a linear programming algorithm is proposed. Considering factors such as Doppler frequency shift, phase-locking scheme, laser relative intensity noise, and phase detector bandwidth, inter-spacecraft offset frequency setting results suitable for the Taiji program are obtained. During the six years of running the detection process, the use of frequency bounds in the range of [5 MHz, 25 MHz] showed that offset frequencies will remain unchanged for a maximum of 1931 days. If the upper and lower bounds are adjusted, and the relative motion between spacecraft is further constrained, the offset frequencies do not need to change during the time of the mission. These results may provide insights into selecting the phase detector and designing operation parameters such as orbit and laser modulation frequency in the Taiji program.

Neutrophil mediated postoperative photoimmunotherapy against melanoma skin cancer.

Surgery is the primary treatment option for most melanoma; however, high tumor recurrence rate after surgical resection becomes the main cause of death in cancer patients. The development of efficient drug delivery nanosystems to inhibit postoperative tumor recurrence becomes very necessary. In the present study, IR780 molecules and TRP-2 peptide were encapsulated in the hydrophobic shell and hydrophilic interior of TAT peptide functionalized liposomes to form TLipIT NPs, which were further internalized into neutrophils (NEs) to achieve TLipIT/NEs. After being intravenously injected into postoperative B16F10-bearing mice, TLipIT/NEs could actively migrate toward the inflamed residual tumor and release TLipIT through neutrophil extracellular traps (NETs). Under NIR laser irradiation, the TLipIT exhibited both photothermal and photodynamic effects to induce immunogenic cell death for maturation of DCs, and simultaneously, to release TRP-2 peptide as a melanoma associated antigen to further strengthen the maturation of DCs, both of which prompts the activation of T cells and induces potent immune responses. TLipIT/NEs hold great potential for the inhibition of postoperative tumor recurrence.

A small-molecule inhibitor of BamA impervious to efflux and the outer membrane permeability barrier.

The development of new antimicrobial drugs is a priority to combat the increasing spread of multidrug-resistant bacteria. This development is especially problematic in gram-negative bacteria due to the outer membrane (OM) permeability barrier and multidrug efflux pumps. Therefore, we screened for compounds that target essential, nonredundant, surface-exposed processes in gram-negative bacteria. We identified a compound, MRL-494, that inhibits assembly of OM proteins (OMPs) by the ß-barrel assembly machine (BAM complex). The BAM complex contains one essential surface-exposed protein, BamA. We constructed a bamA mutagenesis library, screened for resistance to MRL-494, and identified the mutation bamAE470K BamAE470K restores OMP biogenesis in the presence of MRL-494. The mutant protein has both altered conformation and activity, suggesting it could either inhibit MRL-494 binding or allow BamA to function in the presence of MRL-494. By cellular thermal shift assay (CETSA), we determined that MRL-494 stabilizes BamA and BamAE470K from thermally induced aggregation, indicating direct or proximal binding to both BamA and BamAE470K Thus, it is the altered activity of BamAE470K responsible for resistance to MRL-494. Strikingly, MRL-494 possesses a second mechanism of action that kills gram-positive organisms. In microbes lacking an OM, MRL-494 lethally disrupts the cytoplasmic membrane. We suggest that the compound cannot disrupt the cytoplasmic membrane of gram-negative bacteria because it cannot penetrate the OM. Instead, MRL-494 inhibits OMP biogenesis from outside the OM by targeting BamA. The identification of a small molecule that inhibits OMP biogenesis at the cell surface represents a distinct class of antibacterial agents.

Release of cadmium in contaminated paddy soil amended with NPK fertilizer and lime under water management.

Agricultural soils contaminated with cadmium (Cd) pose a risk to receiving surface water via drainage or runoff. A 90-day laboratory incubation experiment was conducted to investigate the release characteristics and transformation of Cd from contaminated paddy soil amended with agrochemical (NPK fertilizer) and lime (L) under water management regimes of continuous flooding (F) and drying-wetting cycles (DW). The result showed that the dissolved Cd concentrations in overlying water of the fertilizer treatment under flooding (NPK+F) and drying-wetting (NPK+DW) reached up to 81.0 µg/L and 276 µg/L, and were much higher than that from the corresponding controls without NPK fertilizer addition at the end of experiment. The Cd concentration showed significantly negative correlation with overlying water pH, but positive correlation with soil redox potential and concentrations of dissolved total nitrogen, sulfate and manganese in overlying water (P < 0.05), indicating that drying-wetting cycles and N fertilizer addition may enhance soil Cd release. The Cd concentrations in overlying water from all treatments except NPK+L+F treatment exceeded the Cd threshold limit of Chinese Environmental Quality Standards for Surface Water (10 µg/L Grade V) and poses potential risk to surface water quality. Meanwhile, the proportion of Cd in the acid-soluble fraction from all incubated soil except NPK+L+F treatment increased compared to before incubation. The results indicated that continuous flooding was a reasonable water management candidate coupled with lime addition for immobilizing soil Cd.

A Primary Screening and Applying of Plant Volatiles as Repellents to Control Whitefly Bemisia tabaci (Gennadius) on Tomato.

With the goal of finding a new way to reduce population densities of Bemisia tabaci biotype Q in greenhouses, seven repellent volatile chemicals and their combinations were screened. The mixture of DLCO (D-limonene, citral and olive oil (63:7:30)) had a better cost performance(SC50 = 22.59 mg/ml)to repel whiteflies from settling than the other mixtures or single chemicals. In the greenhouse, in both the choice test and the no-choice tests, the number of adult whiteflies that settled on 1% DLCO-treated tomato plants was significantly lower than those settling on the control plants for the different exposure periods (P < 0.01). In the choice test, the egg amount on the treated tomato plants was significantly lower (P < 0.01) than that on the control plants, but there was no significant difference (P > 0.05) between the number of eggs on treated and control plants in the no-choice test. Compared with the controls, 1% DLCO did not cause significantly statistic mortality rates (P > 0.05) out of different living stages of B. tabaci. The tests for evaluating the repellent efficacy, showed that a slow-releasing bottle containing the mixture had a period of efficacy of 29 days, and the application of this mixture plus a yellow board used as a push-pull strategy in the greenhouse was also effective.

A comparative study on the effects of excess iodine and herbs with excess iodine on thyroid oxidative stress in iodine-deficient rats.

This study aimed to compare the effect of excess iodine and herbs with excess iodine on treating iodine deficiency-induced goiter from the perspective of oxidative stress and to measure selenium values in Chinese herbs. One hundred twenty 4-week-old Wistar rats were selected and randomly divided into four groups after inducing iodine-deficiency goiter: normal control group (NC), model control group (MC), iodine excess group (IE), and herbs with iodine excess group (HIE). The activities of oxidative enzymes and levels of oxidative products were measured using biochemical tests. The expression of 4-hydroxynonenal (4-HNE) in the thyroid was detected by immunohistochemistry and the expression of peroxiredoxin 5 (PRDX5) by the Western blot and immunohistochemistry. Selenium values in iodine-excessive herbs were measured by hydride generation-atomic fluorescence spectrometry. The herbs with iodine excess were tested to contain rich selenium. The activities of superoxide dismutase (SOD) and PRDX5 increased markedly, and the values of malondialdehyde (MDA) and 4-HNE decreased significantly in the HIE group. In conclusion, compared with excess iodine, herbs with excess iodine damaged thyroid follicular cells less, which may be related to the increase of antioxidant capacity and rich selenium values in iodine-excessive herbs.