Ångstrom‐Scale Silver Particles as a Promising Agent for Low‐Toxicity Broad‐Spectrum Potent Anticancer Therapy

Cancer incidence is rising, and the efficacy of current available anticancer agents is limited by severe dose‐limiting toxicities and drug resistance problems. Nanoparticles are heralded as the next frontier in cancer treatment. Here, a pure physical method is used to efficiently fabricate very small silver particles even approaching the Ångstrom (Ång) dimension. Fructose is used as a dispersant and stabilizer to coat the Ång‐scale silver particles (AgÅPs). Functional and mechanistic studies demonstrate that fructose‐coated AgÅPs (F‐AgÅPs) can enter and accumulate in multiple cultured cancer cell lines to induce apoptotic death, whereas most normal cells are resistant to the efficacious dose of F‐AgÅPs; in vivo, intravenous administration of F‐AgÅPs potently inhibits the growth of pancreatic and lung cancer xenografts in nude mice, without inducing notable toxic effects on the healthy tissues. The results suggest the promising potential of F‐AgÅPs as a potent, safe, and broad‐spectrum agent for the cancer treatment.     

A Low‐Toxic Multifunctional Nanoplatform Based on Cu9S5@mSiO2 Core‐Shell Nanocomposites: Combining Photothermal‐ and Chemotherapies with Infrared Thermal Imaging for Cancer Treatment

Copper chalcogenides have been demonstrated to be a promising photothermal agent due to their high photothermal conversion efficiency, synthetic simplicity, and low cost. However, the hydrophobic and less biocompatible characteristics associated with their synthetic processes hamper widely biological applications. An alternative strategy for improving hydrophilicity and biocompatibility is to coat the copper chalcogenide nanomaterials with silica shell. Herein, the rational preparation design results in successful coating mesoporous silica (mSiO₂) on as‐synthesized Cu₉S₅ nanocrystals, forming Cu₉S₅@mSiO₂‐PEG core‐shell nanostructures. As‐prepared Cu₉S₅@mSiO₂‐PEG core‐shell nanostructures show low cytotoxicity and excellent blood compatibility, and are effectively employed for photothermal ablation of cancer cells and infrared thermal imaging. Moreover, anticancer drug of doxorubicin (DOX)‐loaded Cu₉S₅@mSiO₂‐PEG core‐shell nanostructures show pH sensitive release profile and are therefore beneficial to delivery of DOX into cancer cells for chemotherapy. Importantly, the combination of photothermal‐ and chemotherapies demonstrates better effects of therapy on cancer treatment than individual therapy approaches in vitro and in vivo.     

In vivo Quantum‐Dot Toxicity Assessment

Quantum dots have potential in biomedical applications, but concerns persist about their safety. Most toxicology data is derived from in vitro studies and may not reflect in vivo responses. Here, an initial systematic animal toxicity study of CdSe–ZnS core–shell quantum dots in healthy Sprague–Dawley rats is presented. Biodistribution, animal survival, animal mass, hematology, clinical biochemistry, and organ histology are characterized at different concentrations (2.5–15.0 nmol) over short‐term (<7 days) and long‐term (>80 days) periods. The results show that the quantum dot formulations do not cause appreciable toxicity even after their breakdown in vivo over time. To generalize the toxicity of quantum dots in vivo, further investigations are still required. Some of these investigations include the evaluation of quantum dot composition (e.g., PbS versus CdS), surface chemistry (e.g., functionalization with amines versus carboxylic acids), size (e.g., 2 versus 6 nm), and shape (e.g., spheres versus rods), as well as the effect of contaminants and their byproducts on biodistribution behavior and toxicity. Combining the results from all of these studies will eventually lead to a conclusion regarding the issue of quantum dot toxicity.     

纳米金的制备及在化妆品中的应用初探

采用柠檬酸钠还原氯金酸制备纳米金,利用X射线荧光能谱和透射电子显微镜对产品进行了表征,通过纳米金溶胶及溶胶中含有的柠檬酸钠和保护剂PVP对Hela细胞、CHO细胞的MTT试验,研究了纳米金溶胶及纳米金颗粒对细胞的毒性,结果表明,纳米金溶胶和纳米金颗粒对这两种细胞均没有产生毒性。将纳米金加入到化妆品基础配方中制备得到了稳定的乳状液,为纳米金用于高级化妆品可行性提供部分实验依据。     

Water treatment with silicofluorides and lead toxicity

Toxic metals like lead, manganese, copper and cadmium damage neurons and deregulate neurotransmitters like serotonin and dopamine (which are essential to normal impulse control and learning). Earlier studies show that — controlling for socio‐economic and demographic factors — environmental pollution with lead is a highly significant risk factor in predicting higher rates of crime, attention deficit disorder or hyperactivity, and learning disabilities. Exposure and uptake of lead has been associated with industrial pollution, leaded paint and plumbing systems in old housing, lead residues in soil, dietary habits (such as shortages of calcium and iron), and demographic factors (such as poverty, stress, and minority ethnicity). We report here on an additional “risk co‐factor” making lead and other toxic metals in the environment more dangerous to local residents: the use of silicofluorides as agents in water treatment. The two chemicals in question — fluosilicic acid and sodium silicofluoride — are toxins that, despite claims to the contrary, do not dissociate completely and change water chemistry when used under normal water treatment practices. As a result, water treatment with siliconfluorides apparently functions to increase the cellular uptake of lead. Data from lead screening of over 280,000 children in Massachusetts indicates that silicofluoride usage is associated with significant increases in average lead in children's blood as well as percentage of children with blood lead in excess of 10μg/dL. Consistent with the hypothesized role of silicofluorides as enhancing uptake of lead whatever the source of exposure, children are especially at risk for higher blood lead in those communities with more old housing or lead in excess of 15 ppb in first draw water samples where silicofluorides are also in use. Preliminary findings from county‐level data in Georgia confirm that silicofluoride usage is associated with higher levels of lead in children's blood. In both Massachusetts and Georgia, moreover, behaviors associated with lead nurotoxicity are more frequent in communities using silicofluorides than in comparable localities that do not use these chemicals. Because there has been insufficient animal or human testing of silicofluoride treated water, further study of the effect of silicofluorides is needed to clarify the extent to which these chemicals are risk co‐factors for lead uptake and the hazardous effects it produces.     

Root GS and NADH-GDH Play Important Roles in Enhancing the Ammonium Tolerance in Three Bedding Plants

Ammonium is a paradoxical nutrient because it is more metabolically efficient than nitrate, but also causes plant stresses in excess, i.e., ammonium toxicity. Current knowledge indicates that ammonium tolerance is species-specific and related to the ammonium assimilation enzyme activities. However, the mechanisms underlying the ammonium tolerance in bedding plants remain to be elucidated. The study described herein explores the primary traits contributing to the ammonium tolerance in three bedding plants. Three NH₄⁺:NO₃⁻ ratios (0:100, 50:50, 100:0) were supplied to salvia, petunia, and ageratum. We determined that they possessed distinct ammonium tolerances: salvia and petunia were, respectively, extremely sensitive and moderately sensitive to high NH₄⁺ concentrations, whereas ageratum was tolerant to NH₄⁺, as characterized by the responses of the shoot and root growth, photosynthetic capacity, and nitrogen (amino acid and soluble protein)-carbohydrate (starch) distributions. An analysis of the major nitrogen assimilation enzymes showed that the root GS (glutamine synthetase) and NADH-GDH (glutamate dehydrogenase) activities in ageratum exhibited a dose-response relationship (reinforced by 25.24% and 6.64%, respectively) as the NH₄⁺ level was raised from 50% to 100%; but both enzyme activities were significantly diminished in salvia. Besides, negligible changes of GS activities monitored in leaves revealed that only the root GS and NADH-GDH underpin the ammonium tolerances of the three bedding plants.     

2019—2022年聊城市食品和病例分离单增李斯特菌基于全基因组测序的分子特征及耐药性分析

目的 基于全基因组测序（WGS）比较分析2019—2022年聊城市单核细胞增生李斯特菌（Lm）食品和病例分离株基因组特征、毒力性、耐药性以及遗传多样性。方法 对聊城市33株市售食品和临床病例中Lm分离株开展抗生素敏感性试验和WGS。利用MGAP对WGS数据进行拼接组装,对组装基因组进行基因预测和功能注释、MLST,制作cg MLST最小生成树图,并与美国国家生物信息中心（NCBI）上获取的18株国内外Lm构建wg-SNP进化树。结果 33株Lm分离株的基因组大小为2.89～3.41 Mb,CG含量为37.81%～37.97%,可分为6个ST型（ST9、ST121、ST8、ST87、ST155、ST101）,分别属于6个克隆复合群（CC9、CC121、CC8、CC87、CC155、CC101）;分离株均携带fosX和mprF耐药基因,此外还携带lplA1、prsA2等其他18个毒力基因,有不同程度的毒力基因缺失情况。2株菌对四环素耐药,1株菌对林可霉素耐药。均携带毒力岛LIPI-1和LIPI-2,未检测到毒力岛LIPI-3和LIPI-4。wg-SNPs、cgMLST和基于单拷贝核心蛋白序列的系统发育树遗传进化分析显示,33株Lm分子分型呈现高度多样性,病例来源菌株与食品分离株亲缘关系密切,食品分离株与国外暴发分离株在进化关系上密切相关。结论 山东省聊城市食品和病例中分离的单增李斯特菌均携带毒力基因,具有一定的潜在致病能力,耐药情况尚不严重。分子型别呈现出多样性,食品来源菌株和病例分离株具有较近的亲缘关系,提示市售食品有食源性感染的潜在风险。     

Safety Evaluation of Green Tea Polyphenols Consumption in Middle‐aged Ovariectomized Rat Model

This work evaluates chronic safety in middle‐aged ovariectomized rats supplemented with different dosages of green tea polyphenols (GTP) in drinking water. The experiment used 6‐mo‐old sham (n = 39) and ovariectomized (OVX, n = 143) female rats. All sham (n = 39) and 39 of the OVX animals received no GTP treatment and their samples were collected for outcome measures at baseline, 3 mo, and 6 mo (n = 13 per group for each). The remaining OVX animals were randomized into 4 groups receiving 0.15%, 0.5%, 1%, and 1.5% (n = 26 for each) of GTP (wt/vol), respectively, in drinking water for 3 and 6 mo. No mortality or abnormal treatment‐related findings in clinical observations or ophthalmologic examinations were noted. No treatment‐related macroscopic or microscopic findings were noted for animals administered 1.5% GTP supplementation. Throughout the study, there was no difference in the body weight among all OVX groups. In all OVX groups, feed intake and water consumption significantly decreased with GTP dose throughout the study period. At 6 mo, GTP intake did not affect hematology, clinical chemistry, and urinalysis, except for phosphorus and blood urea nitrogen (increased), total cholesterol, lactate dehydrogenase, and urine pH (decreased). This study reveals that the no‐observed‐adverse‐effect level (NOAEL) of GTP is 1.5% (wt/vol) in drinking water, the highest dose used in this study.     

不同杀菌剂对玉米丝黑穗病原菌室内抑菌作用

采用孢子萌发法测定了戊唑醇、三唑酮、多菌灵和福美双4种杀菌剂对玉米丝黑穗病菌孢子萌发的抑制作用和毒力。结果表明，戊唑醇对玉米丝黑穗病菌孢子的萌发抑制作用最强，EC50为0．0369mg／L，表现出非常高的毒力．显著高于其他3种药剂．是防治该病害非常优秀的杀菌剂。     

pH Responsive Abelmoschus esculentus Mucilage and Administration of Methotrexate: In-Vitro Antitumor and In-Vivo Toxicity Evaluation

The rapid progression in biomaterial nanotechnology apprehends the potential of non-toxic and potent polysaccharide delivery modules to overcome oral chemotherapeutic challenges. The present study is aimed to design, fabricate and characterize polysaccharide nanoparticles for methotrexate (MTX) delivery. The nanoparticles (NPs) were prepared by Abelmoschus esculentus mucilage (AEM) and chitosan (CS) by the modified coacervation method, followed by ultra-sonification. The NPs showed much better pharmaceutical properties with a spherical shape and smooth surface of 213.4–254.2 nm with PDI ranging between 0.279–0.485 size with entrapment efficiency varying from 42.08 ± 1.2 to 72.23 ± 2.0. The results revealed NPs to possess positive zeta potential and a low polydispersity index (PDI). The in-vitro drug release showed a sustained release of the drug up to 32 h with pH-dependence. Blank AEM -CS NPs showed no in-vivo toxicity for a time duration of 14 days, accompanied by high cytotoxic effects of optimized MTX loaded NPs against MCF-7 and MD-MBA231 cells by MTT assay. In conclusion, the findings advocated the therapeutic potential of AEM/CS NPs as an efficacious tool, offering a new perspective for pH-responsive routing of anticancer drugs with tumor cells as a target.