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[Display omitted] As the fourth state of matter, plasma's unique properties and interactions with other states of matter offer many promising opportunities for investigation and discovery. In particular, cold atmospheric plasma (CAP), operating at atmospheric pressure and room temperature, has remarkable potential for biomedical applications through various delivery methods. These biomedical applications include sterilization, wound healing, blood coagulation, oral/dental diseases treatment, cancer therapy, and immunotherapy. Effective delivery of plasma constituents is critical to its efficacy for these applications. Therefore, this review presents the key research activities related to CAP delivery (including direct CAP delivery, delivery of plasma-activated media, biomedical device-assisted plasma delivery, and CAP delivery with other therapeutics) and needs for future research. This review will be of great interest for understanding the current state-of-the-art of biomedical applications of plasma medicine while also giving researchers from a broad range of communities insight into research efforts that would benefit from their contributions. Such communities include biomedicine, physics, biochemistry, material science, nanotechnology, and medical device manufacturing. [ABSTRACT FROM AUTHOR]

Metabolic skeletal disorders remain a major clinical challenge. The complexity of this disease requires a strategy to address the net effects of both inflammation and impaired bone formation. microRNA-based gene therapy provides several therapeutic advantages to tackle these issues. Herein, we describe a microRNA-21 (miR-21) delivery system with an additional therapeutic effect from that of the delivery carrier itself. Poly (salicylic acid) (PSA) is, for the first time, synthesized via polycondensation of salicylic acid (SA), a bioactive ingredient widely used for anti-inflammation in medicine. PSA can self-assemble into nanoparticles (PSA-NPs) and can effectively deliver genes both in vitro and in vivo. The carrier was then attached to repetitive sequences of aspartate, serine, serine (DSS) 6 for delivering miRNAs specifically to bone-formation surfaces. In vitro studies showed that miR-21@PSA-NP could effectively realize the intracellular delivery of miR-21 with low toxicity, while in vivo results indicated that the miR-21@PSA-NP-DSS 6 prolonged blood circulation time, enhanced bone accumulation, and significantly improved the efficacy of miR-21-based bone anabolic therapy in osteoporotic mice. The constructed delivery system (miR-21@PSA-NP-DSS 6) inherited the advantages of both SA and miR-21, which could ameliorate bone-inflamed niche and rescued the impaired bone formation ability. The synergy of anti-inflammatory and pro-osteogenic effects significantly improved trabecular bone microstructure in osteoporotic mice. The complexity of metabolic skeletal disorders requires a strategy to address the net effects of both inflammation and impaired bone formation. microRNA-based gene therapy provides several therapeutic advantages to tackle these issues. We develop a novel microRNA-21 delivery system with additional therapeutic effect from that of the gene carrier itself. Poly (salicylic acid) (PSA) nanoparticles, for the first time, synthesized via polycondensation of salicylic acid and can effectively deliver genes both in vitro and in vivo. The constructed delivery system (miR-21@PSA-NP-DSS 6) inherited the advantages of both SA (commonly used anti-inflammation drug in medicine) and miR-21 (a pro-osteogenic molecule), which could ameliorate bone-inflamed niche, rescued impaired bone formation ability and significantly improved trabecular bone microstructure in osteoporotic mice. [Display omitted] [ABSTRACT FROM AUTHOR]

Mercury (Hg) contamination in paddy soils poses a health risk to rice consumers and the environmental behavior of Hg determines its toxicity. Thus, the variations of Hg speciation are worthy of exploring. In this study, microcosm and pot experiments were conducted to elucidate Hg transformation, methylation, bioaccumulation, and risk coupled with biogeochemical cycling of key elements in a Hg-polluted alkaline paddy soil. In microcosm and pot experiments, organic- and sulfide-bound and residual Hg accounted for more than 98% of total Hg, and total contents of dissolved, exchangeable, specifically adsorbed, and fulvic acid-bound Hg were less than 2% of total Hg, indicating a low mobility and environmental risk of Hg. The decrease of pH aroused from Fe(III), SO 4 2−, and NO 3 − reduction promoted Hg mobility, whereas the increase of pH caused by Fe(II), S2−, and NH 4 + oxidation reduced available Hg contents. Moreover, Fe-bearing minerals reduction and organic matter consumption promoted Hg mobility, whereas the produced HgS and Fe(II) oxidation increased Hg stability. During flooding, a fraction of inorganic Hg (IHg) could be transported into methylmercury (MeHg), and during drainage, MeHg would be converted back into IHg. After planting rice in an alkaline paddy soil, available Hg was below 0.3 mg kg−1. During rice growth, a portion of available Hg transport from paddy soil to rice, promoting Hg accumulation in rice grains. After rice ripening, IHg levels in rice tissues followed the trend: root > leaf > stem > grain, and IHg content in rice grain exceed 0.02 mg kg−1, but MeHg content in rice grain meets daily intake limit (37.45 μg kg−1). These results provide a basis for assessing the environmental risks and developing remediation strategies for Hg-contaminated redox-changing paddy fields as well as guaranteeing the safe production of rice grains. [Display omitted] • Variations of Hg species in microcosm experiment are similar to those in pot experiment. • The organic-, sulfide-bound and residual Hg accounted for more than 98% of total Hg. • TMeHg content increased firstly and then decreased in microcosm and pot experiments. • Available MeHg kept at a low concentration in paddy soil during flooding and drainage. • IHg content in rice grain exceed safe level, but MeHg content meets daily intake limit. [ABSTRACT FROM AUTHOR]

Animal parasitic diseases not only have an economic impact, but also have serious social and public health impacts. Although antiparasitic drugs can treat these diseases, it seems difficult for users to comprehensively utilize the information, due to incomplete and difficult data collection. Thus, there is an urgent need to establish a comprehensive database, that includes parasitic diseases and related drugs. In this paper, we develop a knowledge database dedicated to collecting and analyzing animal parasitic diseases and related drugs, named Animal Parasitic Diseases and Drugs Database (APDDD). The current version of APDDD includes animal parasitic disease data of 8 major parasite classifications that cause common parasitic diseases and 96 subclass samples mined from many literature and authoritative books, as well as 182 antiparasitic drugs. Furthermore, we utilized APDDD data to add a knowledge graph representing the relationships between parasitic diseases, drugs, and the targeted gene of drugs acting on parasites. We hope that APDDD will become a good database for animal parasitic diseases and antiparasitic drugs research and that users can gain a more intuitive understanding of the relationships between parasitic diseases, drugs, and targeted genes through the knowledge graph. • This is the first time that relevant data has been systematically generalized and summarized. • We employed the methodology of knowledge graph to visualize certain data in the database. • This database can become a publicly available gold standard benchmark database. [ABSTRACT FROM AUTHOR]

The paleo-Pearl River has been suggested as one of the major source terrains for the northern South China Sea, which headstreams in the hinterland of the Tibetan Plateau and flows through the South China Block, eventually discharges into the Pearl River Mouth Basin (PRMB) of the South China Sea (SCS). However, the drainage history of the paleo-Pearl River remains a matter of debate. Detrital zircon U Pb ages, trace elements, Nd and Sr isotopes and clay minerals from the Eocene to Miocene sediments in the Pearl River Mouth Basin of the South China Sea have been used to investigate the sedimentary provenance and reconstruct the drainage history of the paleo-Pearl River. The Eu/Eu*, La/Sc, La/Co, Th/Sc and Th/Co ratios, the Hf La/Th and La/Sc-Co/Th diagrams, and the chondrite normalized REE patterns of the samples suggested that the Eocene to Miocene sediments were mainly derived from felsic source rock. The Lower Eocene sediments were mainly provided by the intrabasinal uplift regions. The Dong River and Bei River initiated since Upper Eocene supplied large amounts of felsic detritus from the Southern China Coast to Zhu Ⅰ Depression, and then transported sediments into the Zhu Ⅱ depression during the upper Early Oligocene. The Nd and Sr isotopes of the sediments suggested that the Liu River may not provide sediments for the PRMB, however, the Gui River may have made a very small contribution. The Nd and Sr isotopes of the sediments also suggested that the paleo-Pearl River began to extend westward to form Xi River and eventually the Hongshui River in the Late Oligocene. The trace element ratios of the samples also suggested that the Miocene sediments may have received more input from an intermediate rock area, indicating the main provenance switch from the coast of South China to a northern source during this time. This conclusion has been supported by the detrital zircon U Pb ages, Nd and Sr isotopes and clay minerals data of the samples, which show that the provenance of the sediments supplied by the paleo-Pearl River had an abrupt shift in the Middle Miocene. The southeastern Tibetan Plateau rapid uplifted and experienced erosion in the Middle Miocene, leading to the progressive headward erosion of the Pearl River system into the continental interior. Detrital zircon U Pb ages, trace elements, Nd and Sr isotopes and clay minerals of Eocene to Miocene samples for the PRMB have been used to determine the provenance of the PRMB and reconstruct the evolutionary history of the paleo-Pearl River. The following conclusions can be made: (1) The Oligocene to Miocene sediments transported by the paleo-Pearl River were derived from felsic source rock and the Miocene sediments may have received more input from intermediate rock area. (2) The Liu River might not provide sediments for the PRMB and the Gui River might have made a very small contribution. The paleo-Pearl River began to extend westward to form the Xi River and eventually the Hongshui River was formed during the Late Oligocene. (3) Trace elements and Nd and Sr isotopes of the samples indicated that the western tributaries of the Pearl River did act as important sediment supplier since Early Miocene and lasted to Middle Miocene. (4) The provenance abrupt change in the Middle Miocene probably resulted from the rapid uplift of the southeastern Tibetan Plateau, leading to the progressive headward erosion of the Pearl River system into the continental interior on the basis of the Early Miocene. [ABSTRACT FROM AUTHOR]

Chromium isotopes are promising for monitoring and quantifying the extent of microbial Cr(VI) reduction. However, the mechanisms and factors that influence Cr isotope fractionation are not well understood. In the present study, we investigated the effects of different metabolic pathways and various environmental parameters on Cr isotope fractionation during Cr(VI) reduction by the extremely thermophilic bacterium Caldicellulosiruptor saccharolyticus. The Cr isotopic compositions were measured on unreacted Cr(VI) in the remaining solution. The reaction product is isotopically lighter than the reactant. The Cr isotope composition for remaining Cr(VI) in the solution followed a Rayleigh fractionation trend and thus became increasingly isotopically heavier as the reduction of Cr(VI) proceeded. Cr(VI) reduction mainly occurs on the cell surface by Ni–Fe hydrogenase; however, in the presence of CuCl 2 , the activity of Ni–Fe hydrogenase was inhibited, and Cr(VI) was reduced inside the cells. We found that despite different Cr(VI) reduction locations, Cr isotope enrichment factors (ε = (α − 1) × 1000, where α is the fractionation factor) were identical within uncertainty for experiments with and without CuCl 2 (−2.72 ± 0.67‰ and −2.92 ± 0.14‰, respectively). When added to the cell cultures, neutral red (NR) functioned as an electron carrier that enabled bacteria to drive the electron transfer processes. The ε values were also similar for experiments with and without NR (−2.53 ± 0.40‰ and −2.92 ± 0.14‰, respectively). We compared these ε values to investigate the effects of different electron transport pathways and cellular Cr(VI) transfer processes, including Cr(VI) transport across the cell envelope and binding to reacting enzymes, on Cr isotope fractionation. Furthermore, the effects of various environmental parameters on Cr isotope fractionation were tested, including temperature (50 °C and 70 °C), hydrogen concentration, and different electron donors (glucose and hydrogen). The ε values were similar at both tested temperatures and stayed within the previously observed range for mesophiles; changes in hydrogen concentration also did not affect the ε values. However, the ε values were slightly higher with hydrogen as the electron donor (−3.64 ± 0.24‰) than those with glucose as the electron donor (−2.92 ± 0.14‰). In short, the Cr enrichment factors remained unchanged despite of changing microbial Cr (VI) reduction pathways and changing temperature conditions, but may be sensitive to the electron donor type. [ABSTRACT FROM AUTHOR]

Abstract Chromium isotope fractionation analysis is a promising approach for the assessment of microbial Cr(VI) reduction in groundwater. Understanding the mechanisms and other parameters that control Cr isotope fractionation factors (between the product Cr(III) and reactant Cr (VI)) in microbial Cr(VI) reduction is critical to this application. To date, such studies are very limited. Here, the influence of critical factors on observed Cr isotope fractionation during Cr(VI) reduction by Shewanella oneidensis MR-1 under various conditions was investigated. The Cr(VI) concentration and Cr isotope ratio measurements were conducted on unreacted Cr(VI) remaining in solution to determine Cr isotope fractionation factors. The changes in ambient environmental conditions (e.g., pH, temperature) have limited influence on Cr isotope fractionation factors. However, as a result of Cr(VI) consumption as the experiments proceed, the change in bioavailability of Cr(VI) has a significant impact on Cr isotope fractionation factors. For example, in temperature-controlled experiments, Cr isotope fractionation showed two-stage behavior: during Stage I, the values of ε were −2.81 ± 0.19‰ and −2.60 ± 0.14‰ at 18 °C and 34 °C, respectively; during Stage II, as Cr(VI) reduction progressed, Cr isotope fractionation was significantly masked, and the ε values decreased to −0.98 ± 0.49‰ and −1.01 ± 0.11‰ at 18 °C and 34 °C, respectively. Similar two-stage isotope fractionation behaviors were observed in pH-controlled experiments (pH = 6.0 and 7.2) and in experiments with and without the addition of a competing electron acceptor (nitrate). Masking of isotope fractionation in Stage II indicated restrictions on the bioavailability of Cr(VI) and mass-transfer limitations. This study provides an explanation for the variation in Cr isotope fractionation factors during microbial Cr(VI) reduction in the environment, furthering the viability of Cr isotope ratio analysis as an approach in understanding Cr biogeochemical cycling. Graphical abstract Image 1 Highlights • Two-stage process of microbially induced Cr isotope fractionation was revealed. • The suppression of fractionation was attributed to mass-transfer limitations. • Temperature and pH have limited influence on microbially induced fractionation. • The values of ε were similar in the presence or in the absence of nitrate. [ABSTRACT FROM AUTHOR]

Drug-eluting stents are the most commonly employed method to control post-angioplasty restenosis. Unfortunately, they exacerbate life-threatening stent thrombosis because of endothelium damage caused by both drug and stenting. To solve this major medical problem, an endothelium-protective and stent-free anti -restenotic method is highly desirable. Here we have generated a biomimetic intravenous delivery system using dendritic polymer-based nanoclusters, which were coated with platelet membranes for targeting to the injured arterial wall where restenosis occurs. These nanoclusters were loaded with an endothelium-protective epigenetic inhibitor (JQ1) or an endothelium-toxic status quo drug (rapamycin), and compared for their ability to mitigate restenosis without hindering the process of re-endothelialization. Fluorescence imaging of Cy5-tagged biomimetic nanoclusters indicated their robust homing to injured, but not uninjured arteries. Two weeks after angioplasty, compared to no-drug control, both rapamycin- and JQ1-loaded biomimetic nanoclusters substantially reduced (by >60%) neointimal hyperplasia, the primary cause of restenosis. However, whereas the rapamycin formulation impaired the endothelial re-coverage of the denuded inner arterial wall, the JQ1 formulation preserved endothelial recovery. In summary, we have created an endothelium-protective anti -restenotic system with biomimetic nanoclusters containing an epigenetic inhibitor. This system warrants further development for a non-thrombogenic and stent-free method for clinical applications. [ABSTRACT FROM AUTHOR]

An efficient palladium/copper-catalyzed tandem Sonogashira reaction/lactonization of methyl 2-(2′,2′-dibromovinyl)benzoate with terminal alkynes has been developed. This facile and direct approach furnishes a variety of 3-alkynyl isocoumarins in moderate to good yields under mild reaction conditions. Furthermore, this method enables concise total synthesis of natural products 3′-hydroxycorfin and gymnopalynes A. [ABSTRACT FROM AUTHOR]

Polymeric unimolecular nanoparticles (NPs) exhibiting a core-shell structure and formed by a single multi-arm molecule containing only covalent bonds have attracted increasing attention for numerous biomedical applications. This unique single-molecular architecture provides the unimolecular NP with superior stability both in vitro and in vivo, a high drug loading capacity, as well as versatile surface chemistry, thereby making it a desirable nanoplatform for therapeutic and diagnostic applications. In this review, we surveyed the architecture of various types of polymeric unimolecular NPs, including water-dispersible unimolecular micelles and water-soluble unimolecular NPs used for the delivery of hydrophobic and hydrophilic agents, respectively, as well as their diverse biomedical applications. Future opportunities and challenges of unimolecular NPs were also briefly discussed. [ABSTRACT FROM AUTHOR]

Greenhouse gas (GHG) emissions from oil and gas exploration and development are major contributors to emission inventories in oil and natural gas (ONG) systems. For the developing countries, including China, studies of this aspect of the industry, being at an early stage, lack a unified method of calculation, and this leads to varied projections of national emissions. In this paper, progress is reported on direct measurement of CH 4 and CO 2 emissions along the oil and gas value chain, for four oil and gas fields. An improved calculation method (classification calculation method), which considers the production status of each type of oil and gas field in China, is proposed for the first time in this study. Based on in situ measurement, it is used to estimate the national CH 4 and CO 2 emissions from the process of petroleum exploration and development. The results showed that CH 4 and CO 2 emissions in 2013 were 73.29 × 10 4 and 20.32 × 10 4 tonnes, respectively (in CO 2 equivalent: 1559.36 × 10 4 tonnes). Compared with the results (731.52 × 10 4 tonnes of CH 4 , 1031.55 × 10 4 tonnes of CO 2 , 16,393.48 × 10 4 tonnes of CO 2 equivalent) in 2013 determined by the Tier 1 method of the Intergovernmental Panel on Climate Change (IPCC), the carbon emissions from field measurement method were much lower than that of IPCC method, which indicated that carbon emissions of ONG systems in China were severely overrated by IPCC. Hence, the GHG emission results reported herein could fundamentally improve the knowledge and understanding of GHG emissions from ONG exploration and development in China. [ABSTRACT FROM AUTHOR]

• Bus bunching occurs much fewer in observations than in conventional models. • Counteraction between link and stop headway deviations can resist bus bunching. • Superposition between link and stop headway deviations destroys headway regularity. • Counteraction is more prominent than superposition with buses moving forward. • The counteraction effect owes to drivers' reactions to bus travel time deviations. Bus headway deviations are the major causes of bus bunching, which is detrimental to bus service reliability and leads to excessive waiting time for passengers. Generally, it is believed that bus bunching is an inevitable result once a service disturbance occurs, as long as the route is long enough. However, in this study, it goes as low as 5% of all trips from the empirical data, contradicting the expectation in theory. This study explores the underlying reasons for this contradiction based on empirical data from two representative bus routes in China. The results show that headway deviations on links and at stops mostly counteract with each other, constraining the occurrence of bus bunching. Under this counteraction effect, the path headway deviations remain within a stable range, normally bounded by the planned headway. It indicates that the bus system has a self-repair ability to resist headway disruptions, which explains why bus bunching happens at a considerably lower frequency in practice than in theory. We further discuss how the counteraction effect works. The insights gained from this study can shed light on preventing bus bunching and generating new ways to recover bus service regularity after a headway disruption. If we can adequately adjust the control methods to make the link and stop headway deviations counteract with each other, the bus system can automatically mitigate the headway deviations. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer for which there is no available targeted therapy. TNBC cases contribute disproportionately to breast cancer-related mortality, thus the need for novel and effective therapeutic methods is urgent. We have previously shown that a National Cancer Institute (NCI) investigational drug aminoflavone (AF) exhibits strong growth inhibitory effects in TNBC cells. However, in vivo pulmonary toxicity resulted in withdrawal or termination of several human clinical trials for AF. Herein we report the in vivo efficacy of a nanoformulation of AF that enhances the therapeutic index of AF in TNBC. We engineered a unique unimolecular micelle nanoparticle (NP) loaded with AF and conjugated with GE11, a 12 amino acid peptide targeting epidermal growth factor receptor (EGFR), since EGFR amplification is frequently observed in TNBC tumors. These unimolecular micelles possessed excellent stability and preferentially released drug payload at endosomal pH levels rather than blood pH levels. Use of the GE11 targeting peptide resulted in enhanced cellular uptake and strong growth inhibitory effects in TNBC cells. Further, AF-loaded, GE11-conjugated (targeted) unimolecular micelle NPs significantly inhibit orthotopic TNBC tumor growth in a xenograft model, compared to treatment with AF-loaded, GE11-lacking (non-targeted) unimolecular micelle NPs or free AF. Interestingly, the animals treated with AF-loaded, targeted NPs had the highest plasma and tumor level of AF among different treatment groups yet exhibited no increase in plasma aspartate aminotransferase (AST) activity level or observable tissue damage at the time of sacrifice. Together, these results highlight AF-loaded, EGFR-targeted unimolecular micelle NPs as an effective therapeutic option for EGFR-overexpressing TNBC. [ABSTRACT FROM AUTHOR]

Neuroendocrine (NE) cancers can cause significant patient morbidity. Besides surgery, there are no curative treatments for NE cancers and their metastases, emphasizing the need for the development of other forms of therapy. In this study, multifunctional unimolecular micelles were developed for targeted NE cancer therapy. The unimolecular micelles were formed by multi-arm star amphiphilic block copolymer poly(amidoamine)–poly(valerolactone)–poly(ethylene glycol) conjugated with KE108 peptide and Cy5 dye (abbreviated as PAMAM–PVL–PEG–KE108/Cy5). The unimolecular micelles with a spherical core–shell structure exhibited a uniform size distribution and excellent stability. The hydrophobic drug thailandepsin-A (TDP-A), a recently discovered HDAC inhibitor, was physically encapsulated into the hydrophobic core of the micelles. KE108 peptide, a somatostatin analog possessing high affinity for all five subtypes of somatostatin receptors (SSTR 1–5), commonly overexpressed in NE cancer cells, was used for the first time as an NE cancer targeting ligand. KE108 exhibited superior targeting abilities compared to other common somatostatin analogs, such as octreotide, in NE cancer cell lines. The in vitro assays demonstrated that the TDP-A-loaded, KE108-targeted micelles exhibited the best capabilities in suppressing NE cancer cell growth. Moreover, the in vivo near-infrared fluorescence imaging on NE-tumor-bearing nude mice showed that KE108-conjugated micelles exhibited the greatest tumor accumulation due to their passive targeting and active targeting capabilities. Finally, TDP-A-loaded and KE108-conjugated micelles possessed the best anticancer efficacy without detectable systemic toxicity. Thus, these novel TDP-A-loaded and KE108-conjugated unimolecular micelles offer a promising approach for targeted NE cancer therapy. [ABSTRACT FROM AUTHOR]