Photocatalytic Aptamer Chemiluminescent System for a Homogeneous, Reliable, Label-Free, Generic Assay of Small Molecules.

Chemiluminescence is a powerful analytical technique with many advantages, while aptamers are well-known as good molecular recognition units. However, many aptamer-based chemiluminescence assays employed interface sensing, which often needed several immobilization, separation, and washing steps. To minimize the risks of contamination and false-positive, we for the first time proposed a photocatalytic aptamer chemiluminescent system for a homogeneous, label-free, generic assay of small molecules. After binding to a DNA aptamer, thioflavin T has a unique photocatalytic oxidase activity to activate the system's luminol chemiluminescence. Then, the specific binding between the aptamer and target molecules will compete with the above process. Therefore, we can realize the efficient assay of different analytes including estradiol and adenosine. Such a homogeneous chemiluminescent system allowed a direct assay of small molecules with limits of detection in a nM level. Several control tests were carried out to avoid possible false-positive results, which were originated from the interactions between analytes and sensing interfaces previously. This homogeneous chemiluminescent system provides a useful strategy to reliably assay various analytes in the pharmacy or biology field.

Higher Toxicity of Gaseous Organics Relative to Particulate Matters Emitted from Typical Cooking Processes.

Cooking emission is known to be a significant anthropogenic source of air pollution in urban areas, but its toxicities are still unclear. This study addressed the toxicities of fine particulate matter (PM2.5) and gaseous organics by combining chemical fingerprinting analysis with cellular assessments. The cytotoxicity and reactive oxygen species activity of gaseous organics were ∼1.9 and ∼8.3 times higher than those of PM2.5, respectively. Moreover, these values of per unit mass PM2.5 were ∼7.1 and ∼15.7 times higher than those collected from ambient air in Shanghai. The total oleic acid equivalent quantities for carcinogenic and toxic respiratory effects of gaseous organics, as estimated using predictive models based on quantitative structure-property relationships, were 1686 ± 803 and 430 ± 176 µg/mg PM2.5, respectively. Both predicted toxicities were higher than those of particulate organics, consistent with cellular assessment. These health risks are primarily attributed to the high relative content and toxic equivalency factor of the organic compounds present in the gas phase, including 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, 2-ethylhexanoic acid, and 2-phenoxyethoxybenzene. Furthermore, these compounds and fatty acids were identified as prominent chemical markers of cooking-related emissions. The obtained results highlight the importance of control measures for cooking-emitted gaseous organics to reduce the personal exposure risks.

Versatile DNA Balances via Adjacent Base Stacking for Homogeneous Assay of Energy Parameters, Small Molecules, And Ribonuclease.

Homogeneous assays often obviate any separation and washing steps, thus minimizing the risks of contamination and false positive. DNA toehold exchange is a homogeneous, reversible process whose thermodynamic properties can be finely tuned for various assay applications. However, the developed probes often rely on direct interactions of analytes with DNA strands involved in toehold exchange, limiting the versatility of probe design. Here, the coaxial adjacent stacking between one auxiliary strand and another invading strand offers a favorable ΔG to shift one DNA balance, while the auxiliary strand is independent of the DNA balance itself. Therefore, such a DNA balance allowed fine tuning of the equilibrium via adjustment of the auxiliary strand alone. The energy contribution of base stacking can be quantified in a homogeneous solution based on the difference in the equilibrium constant. Besides, the proof of concept for DNA balance allows effective assay of a small molecule or ribonuclease in a homogeneous solution. This novel DNA balance via adjacent base stacking provides an interesting alternative to homogeneously assay various analytes.

Nanotechnology prospects in brain therapeutics concerning gene-targeting and nose-to-brain administration.

Neurological diseases are one of the most pressing issues in modern times worldwide. It thus possesses explicit attention from researchers and medical health providers to guard public health against such an expanding threat. Various treatment modalities have been developed in a remarkably short time but, unfortunately, have yet to lead to the wished-for efficacy or the sought-after clinical improvement. The main hurdle in delivering therapeutics to the brain has always been the blood-brain barrier which still represents an elusive area with lots of mysteries yet to be solved. Meanwhile, nanotechnology has emerged as an optimistic platform that is potentially holding the answer to many of our questions on how to deliver drugs and treat CNS disorders using novel technologies rather than the unsatisfying conventional old methods. Nanocarriers can be engineered in a way that is capable of delivering a certain therapeutic cargo to a specific target tissue. Adding to this mind-blowing nanotechnology, the revolutionizing gene-altering biologics can have the best of both worlds, and pave the way for the long-awaited cure to many diseases, among those diseases thus far are Alzheimer's disease (AD), brain tumors (glioma and glioblastoma), Down syndrome, stroke, and even cases with HIV. The review herein collects the studies that tested the mixture of both sciences, nanotechnology, and epigenetics, in the context of brain therapeutics using three main categories of gene-altering molecules (siRNA, miRNA, and CRISPR) with a special focus on the advancements regarding the new favorite, intranasal route of administration.

Microbial Dimethylsulfoniopropionate Cycling in Deep Sediment of the Mariana Trench.

Dimethylsulfoniopropionate (DMSP) and related organic sulfur compounds play key roles in global sulfur cycling. Bacteria have been found to be important DMSP producers in seawater and surface sediments of the aphotic Mariana Trench (MT). However, detailed bacterial DMSP cycling in the Mariana Trench subseafloor remains largely unknown. Here, the bacterial DMSP-cycling potential in a Mariana Trench sediment core (7.5 m in length) obtained at a 10,816-m water depth was investigated using culture-dependent and -independent methods. The DMSP content fluctuated along the sediment depth and reached the highest concentration at 15 to 18 cm below the seafloor (cmbsf). dsyB was the dominant known DMSP synthetic gene, existing in 0.36 to 1.19% of the bacteria, and was identified in the metagenome-assembled genomes (MAGs) of previously unknown bacterial DMSP synthetic groups such as Acidimicrobiia, Phycisphaerae, and Hydrogenedentia. dddP, dmdA, and dddX were the major DMSP catabolic genes. The DMSP catabolic activities of DddP and DddX retrieved from Anaerolineales MAGs were confirmed by heterologous expression, indicating that such anaerobic bacteria might participate in DMSP catabolism. Moreover, genes involved in methanethiol (MeSH) production from methylmercaptopropionate (MMPA) and dimethyl sulfide (DMS), MeSH oxidation, and DMS production were highly abundant, suggesting active conversions between different organic sulfur compounds. Finally, most culturable DMSP synthetic and catabolic isolates possessed no known DMSP synthetic and catabolic genes, and actinomycetes could be important groups involved in both DMSP synthesis and catabolism in Mariana Trench sediment. This study extends the current understanding of DMSP cycling in Mariana Trench sediment and highlights the need to uncover novel DMSP metabolic genes/pathways in extreme environments. IMPORTANCE Dimethylsulfoniopropionate (DMSP) is an abundant organosulfur molecule in the ocean and is the precursor for the climate-active volatile gas dimethyl sulfide. Previous studies focused mainly on bacterial DMSP cycling in seawater, coastal sediment, and surface trench sediment samples, but DMSP metabolism in the Mariana Trench (MT) subseafloor sediments remains unknown. Here, we describe the DMSP content and metabolic bacterial groups in the subseafloor of the MT sediment. We found that the tendency for vertical variation of the DMSP content in the MT was distinct from that of the continent shelf sediment. Although dsyB and dddP were the dominant DMSP synthetic and catabolic genes in the MT sediment, respectively, both metagenomic and culture methods revealed multiple previously unknown DMSP metabolic bacterial groups, especially anaerobic bacteria and actinomycetes. The active conversion of DMSP, DMS, and methanethiol may also occur in the MT sediments. These results provide novel insights for understanding DMSP cycling in the MT.

Role of Nanomedicine-Based Therapeutics in the Treatment of CNS Disorders.

Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Nanotechnology-based medicinal approaches deliver valuable cargos targeting molecular and cellular processes with greater safety, efficacy, and specificity than traditional approaches. CNS diseases include a wide range of brain ailments connected to short- and long-term disability. They affect millions of people worldwide and are anticipated to become more common in the coming years. Nanotechnology-based brain therapy could solve the BBB problem. This review analyzes nanomedicine's role in medication delivery; immunotherapy, chemotherapy, and gene therapy are combined with nanomedicines to treat CNS disorders. We also evaluated nanotechnology-based approaches for CNS disease amelioration, with the intention of stimulating the immune system by delivering medications across the BBB.

Simulation-Guided Rational Design of DNA Probe for Accurate Discrimination of Single-Nucleotide Variants Based on "Hill-Type" Cooperativity.

The accurate discrimination of single-nucleotide variants is of great interest for disease diagnosis and clinical treatments. In this work, a unique DNA probe with "Hill-type" cooperativity was first developed based on toehold-mediated strand displacement processes. Under simulation, this probe owns great thermodynamics advantage for specificity due to two mismatch bubbles formed in the presence of single-nucleotide variants. Besides, the strategies of ΔG' = 0 and more competitive strands are also beneficial to discriminate single-nucleotide variants. The feasibility of this probe was successfully demonstrated in consistent with simulation results. Due to "Hill-type" cooperativity, the probe allows a steeper dynamic range compared with previous probes. With simulation-guided rational design, the resulting probe can accurately discriminate single-nucleotide variants including nucleotide insertions, mutation, and deletions, which are arbitrarily distributed in target sequence. Two specificity parameters were calculated to quantitatively evaluate its good discrimination ability. Hence, "Hill-type" cooperativity can serve as a novel strategy in DNA probe's design for accurate discrimination of single-nucleotide variants.

Biological effects of gamma-ray radiation on tulip (Tulipa gesneriana L.).

Tulip, being an important ornamental plant, generally requires lengthy and laborious procedures to develop new varieties using traditional breeding methods requires. But ionizing radiation potentially accelerates the breeding process of ornamental plant species. The biological effects of γ-ray irradiation on tulip, therefore, were investigated through establishing an irradiation-mediated mutation breeding protocol to accelerate its breeding process. ISSR-PCR molecular marker technique was further used to identify the mutants of phenotypic variation plants. This study showed that low irradiation doses (5 Gy) stimulated bulb germination to improve the survival rate of tulip, while high irradiation doses (20 to 100 Gy) significantly (P < 0.05) inhibited its seed germination and growth, and decreased the flowering rate, petal number, flower stem length and flower diameter. More than 40 Gy significantly (P < 0.05) decreased the total chlorophyll content and increased the malondialdehyde (MDA) content in tulips. Interestingly, three types of both stigma variations and flower pattern variations, and four types of flower colour variations were observed. With increasing the irradiation dose from 5 to 100 Gy, the anthocyanin and flavonoid contents continuously decreased. Scanning electron microscopy (SEM) analysis evidenced that high irradiation doses altered the micromorphology of leaf stomata. Microscopic observations of tulip root apical mitosis further showed the abnormal chromosomal division behaviour occurring at different mitotic phases under irradiation treatment (80 Gy). Increasing the irradiation dose from 20 to 100 Gy enhanced the micronucleus rate. Moreover, the suspected genetic variation in tulips was evaluated by inter-simple sequence repeat (ISSR) analysis, and the percentage of polymorphic bands was 68%. Finally, this study concludes that that 80 Gy may be an appropriate radiation does to better enhance the efficiency of mutagenic breeds in tulip plants. Using γ-ray irradiation, therefore, is expected to offer a theoretical basis for mutation breeding in tulips.

Leukemic progenitor cells enable immunosuppression and post-chemotherapy relapse via IL-36-inflammatory monocyte axis.

Chemotherapy can effectively reduce the leukemic burden and restore immune cell production in most acute myeloid leukemia (AML) cases. Nevertheless, endogenous immunosurveillance usually fails to recover after chemotherapy, permitting relapse. The underlying mechanisms of this therapeutic failure have remained poorly understood. Here, we show that abnormal IL-36 production activated by NF-κB is an essential feature of mouse and human leukemic progenitor cells (LPs). Mechanistically, IL-36 directly activates inflammatory monocytes (IMs) in bone marrow, which then precludes clearance of leukemia mediated by CD8+ T cells and facilitates LP growth. While sparing IMs, common chemotherapeutic agents stimulate IL-36 production from residual LPs via caspase-1 activation, thereby enabling the persistence of this immunosuppressive IL-36­IM axis after chemotherapy. Furthermore, IM depletion by trabectedin, with chemotherapy and PD-1 blockade, can synergistically restrict AML progression and relapse. Collectively, these results suggest inhibition of the IL-36­IM axis as a potential strategy for improving AML treatment.

Chemical Fingerprinting of HULIS in Particulate Matters Emitted from Residential Coal and Biomass Combustion.

Identification of humic-like substances (HULIS) structures and components is still a major challenge owing to their chemical complexity. This study first employed a complementary method with the combination of two-dimensional gas chromatography-time-of-flight mass spectrometry and liquid chromatography-quadrupole-time-of-flight mass spectrometry to address low-polarity and polar components of HULIS in PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 µm), respectively. The combination method showed a significant correlation in identifying overlapping species and performed well in uncovering the chemical complexity of HULIS. A total of 1246 compound species in HULIS (65.6-81.0% for each sample), approximately 1 order of magnitude more compounds than that reported in previous studies, were addressed in PM2.5 collected in real-world household biomass and coal combustion. Aromatics were the most abundant compounds (37.4-64.1% in biomass and 34.5-70.0% in coal samples) of the total mass in all HULIS samples according to carbon skeleton determination, while the major components included phenols (2.6-21.1%), ketones (6.0-17.1%), aldehydes (1.1-6.8%), esters (2.9-20.0%), amines/amides (3.2-8.5%), alcohols (3.8-17.0%), and acids (4.7-15.1%). Among the identified HULIS species, 11-36% mass in biomass and 11-41% in coal were chromophores, while another 22-35 and 23-29% mass were chromophore precursors, respectively. The combination method shows promise for uncovering HULIS fingerprinting.

Using Both Lactic Dehydrogenase Levels and the Ratio of Involved to Uninvolved Free Light Chain Levels as Risk Factors Improves Risk Assessment in Patients With Newly Diagnosed Multiple Myeloma.

BACKGROUND: This study aimed to evaluate the prognostic value of the ratio of involved to uninvolved free light chain (rFLC) levels and lactic dehydrogenase (LDH) levels in the risk stratification of patients with multiple myeloma (MM). MATERIALS AND METHODS: Clinical data of 283 patients with newly diagnosed MM were retrospectively analyzed. RESULTS: In the traditional chemotherapy group, patients with an rFLC < 100 had a better prognosis than those with an rFLC ≥ 100 (40 months versus 6 months, P = 0.022), as did patients with an LDH ≤ upper limit of normal (ULN) compared to those with an LDH > ULN (29 months versus 6 months, P = 0.023). In patients who underwent novel drug-combined therapy, no significant difference was observed between the rFLC < 100 group and the rFLC ≥ 100 group (54 months versus median not reached, P = 0.508). However, patients with an LDH ≤ ULN had a better prognosis than those with an LDH > ULN (60 months versus 21 months, P = 0.004). Using an rFLC ≥ 100 and an LDH ≥ ULN as adverse risk factors, patients were classified into 3 groups: group 1 (no adverse risk factors), group 2 (1 adverse risk factor) and group 3 (2 adverse risk factors). The median overall survival (OS) of groups 1, 2 and 3 was 52 months, 34 months and 15 months, respectively (P = 0.001). CONCLUSIONS: rFLC and LDH levels were sensitive prognostic factors in MM patients, combining them could improve the risk stratification and treatment choice of patients in clinical practice.

[Involvement of p38-p53 signal pathway in resveratrol-induced apoptosis in MCF-7 cells].

This paper is to report the study of resveratrol-induced apoptosis and its mechanisms in MCF-7 cells. MTT assay was performed to assess the cytotoxicity of resveratrol on MCF-7 cells. Hoechst 33258 staining was used to observe cellular morphologic changes in apoptosis. Apoptosis was measured by flow cytometric analysis and the protein expression was examined by Western blotting analysis. The results indicated that resveratrol could inhibit MCF-7 cell growth in a time- and concentration-dependent manner. Remarkable morphologic changes in the cells after 60 micromol L(-1) resveratrol treatment, including cell nuclear shrinkage, DNA condensation and apoptotic bodies, were observed by Hoechst 33258 staining. Resveratrol could induce apoptosis and activate p38 and p53 in a time dependent manner in MCF-7 cells. In addition, the cell growth inhibitory ratio and the apoptotic ratio of resveratrol-treated group decreased markedly by the p38 MAPK inhibitor SB203580 or p53 inhibitor pifithrin-alpha. Further experiments confirmed that resveratrol-induced p53 activation was reduced by SB203580 whereas the activation of p38 was not affected by pifithrin-alpha. In conclusion, resveratrol induced apoptosis in MCF-7 cells could be through activating p38-p53 signal pathway.