Sonodynamic therapy (SDT) is a burgeoning modality for cancer therapy owing to its high tissue-penetrating capability, controllability and safety. Whereas, the undesirable reactive oxygen species ...(ROS) yield of sonosensitizers and tumor hypoxia are two vulnerable spots of SDT. Therefore, it is an advisable strategy to augment ROS level and simultaneously relieve hypoxia for SDT to arrive its full potential in cancer treatment. In this work, the defected two-dimensional (2D) Pd/H-TiO.sub.2 nanosheets (NSs) with triple antineoplastic properties were dexterously elaborated and engineered using a facile one-pot Pd-catalyzed hydrogenation tactic by loading a tiny amount of Pd and then inletting hydrogen flow at atmospheric pressure and temperature. The 2D black Pd/H-TiO.sub.2 NSs with oxygen defects exerted eximious SDT effect based on the decreased bandgap that made it easier for the separation of electrons and holes when triggered by ultrasound as theoretically guided by density functional theory calculations. Additionally, Pd/H-TiO.sub.2 NSs could serve as Fenton-like agents because of the presence of oxygen defects, facilitating the conversion of hydrogen peroxide into hydroxyl radicals for exerting the chemodynamic therapy (CDT). Simultaneously, the introduced tiny Pd component possessed catalase-like activity responsible for oxygen production to ameliorate hypoxic condition and thus contributed to improving SDT and CDT efficacies. Both in vitro and in vivo results provided compelling evidences of high ROS yield and aggrandized sono-chemodynamic effect of Pd/H-TiO.sub.2 nanosonosensitizers with the detailed underlying mechanism investigation by RNA sequencing. This work delves the profound potential of Pd-catalyzed hydrogenated TiO.sub.2 on oncotherapy, and the effective antineoplastic performance and ignorable therapeutic toxicity make it a powerful competitor among a cornucopia of nanosonosensitizers.
Understanding the atmospheric new particle formation (NPF) process within the global range is important for revealing the budget of atmospheric aerosols and their impacts. We investigated the ...seasonal characteristics of NPF in the urban environment of Beijing. Aerosol size distributions down to ∼1 nm and H2SO4 concentration were measured during 2018–2019. The observed formation rate of 1.5 nm particles (J 1.5) is significantly higher than those in the clean environment, e.g., Hyytiälä, whereas the growth rate is not significantly different. Both J 1.5 and NPF frequency in urban Beijing show a clear seasonal variation with maxima in winter and minima in summer, while the observed growth rates are generally within the same range around the year. We show that ambient temperature is a governing factor driving the seasonal variation of J 1.5. In contrast, the condensation sink and the daily maximum H2SO4 concentration show no significant seasonal variation during the NPF periods. In all four seasons, condensation of H2SO4 and (H2SO4) n (amine) n clusters contributes significantly to the growth rates in the sub-3 nm size range, whereas it is less important for the observed growth rates of particles above 3 nm. Therefore, other species are always needed for the growth of larger particles.
PM2.5 during severe winter haze in Beijing, China, has reached levels as high as 880 μg/m3, with sulfur compounds contributing significantly to PM2.5 composition. This sulfur has been traditionally ...assumed to be sulfate, although atmospheric chemistry models are unable to account for such large sulfate enhancements under dim winter conditions. Using a 1‐D model, we show that well‐characterized but previously overlooked chemistry of aqueous‐phase HCHO and S(IV) in cloud droplets to form a S(IV)‐HCHO adduct, hydroxymethane sulfonate, may explain high particulate sulfur in wintertime Beijing. We also demonstrate in the laboratory that methods of ion chromatography typically used to measure ambient particulates easily misinterpret hydroxymethane sulfonate as sulfate. Our findings suggest that HCHO and not SO2 has been the limiting factor in many haze events in Beijing and that to reduce severe winter pollution in this region, policymakers may need to address HCHO sources such as transportation.
Plain Language Summary
Air pollution in Beijing is especially severe in winter, when concentrations of tiny particles in the air can reach concentrations over 20 times greater than the safe level recommended by the World Health Organization. In these severe pollution episodes, observations show that a large portion of the particles is made up of sulfur. Scientists have assumed that this sulfur is in the form of sulfate; however, computer simulations of air pollution chemistry have been unable to explain such high sulfate concentrations. We show with a simple computer simulation that a large portion of the sulfur in these haze episodes may, instead of sulfate, actually be a molecule called hydroxymethane sulfonate, which is formed by a chemical reaction in cloud droplets of dissolved formaldehyde with dissolved sulfur dioxide. We also show in laboratory experiments that the machines typically used for determining the chemical composition of particles easily misinterpret hydroxymethane sulfonate as sulfate. Importantly, the chemistry that produces hydroxymethane sulfonate is usually limited by formaldehyde, implying that reductions in sulfur dioxide would be ineffective at reducing severe haze. Instead, focusing future emissions reductions on formaldehyde emissions may be an effective way to curtail severe winter haze in the Beijing area.
Key Points
Chemistry models have been unable to explain high levels of observed particulate sulfur, usually interpreted as sulfate, during Beijing winter haze events
Typical measurement systems for ambient particulates easily misinterpret hydroxymethane sulfonate (HMS) as sulfate
HMS may comprise a large portion of particulate sulfur during extreme haze, implying that HCHO, rather than SO2, would be a limiting factor for such events
SO2 concentration decreased rapidly in recent years in China due to the implementation of strict control policies by the government. Particulate sulfate (pSO42−) and gaseous H2SO4 (SA) are two major ...products of SO2 and they play important roles in the haze formation and new particle formation (NPF), respectively. We examined the change in pSO42− and SA concentrations in response to reduced SO2 concentration using long-term measurement data in Beijing. Simulations from the Community Multiscale Air Quality model with a 2-D Volatility Basis Set (CMAQ/2D-VBS) were used for comparison. From 2013 to 2018, SO2 concentration in Beijing decreased by ~81% (from 9.1 ppb to 1.7 ppb). pSO42− concentration in submicrometer particles decreased by ~60% from 2012–2013 (monthly average of ~10 μg·m−3) to 2018–2019 (monthly average of ~4 μg·m−3). Accordingly, the fraction of pSO42− in these particles decreased from 20–30% to <10%. Increased sulfur oxidation ratio was observed both in the measurements and the CMAQ/2D-VBS simulations. Despite the reduction in SO2 concentration, there was no obvious decrease in SA concentration based on data from several measuring periods from 2008 to 2019. This was supported by the increased SA:SO2 ratio with reduced SO2 concentration and condensation sink. NPF frequency in Beijing between 2004 and 2019 remains relatively constant. This constant NPF frequency is consistent with the relatively stable SA concentration in Beijing, while different from some other cities where NPF frequency was reported to decrease with decreased SO2 concentrations.
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•Particulate sulfate concentration and its fraction in submicrometer particles decreased from 2012 to 2019 in Beijing.•Sulfur oxidation ratio increased from 2013 to 2019 in Beijing.•Sulfuric acid concentration remains relatively stable based on several measuring periods from 2008 to 2019.•The frequency of new particle formation events in Beijing remains relatively stable from 2004 to 2019.
Due to the specific advantages of ultrasound (US) in therapeutic disease treatments, the unique therapeutic US technology has emerged. In addition to featuring a low‐invasive targeted cancer‐cell ...killing effect, the therapeutic US technology has been demonstrated to modulate the tumor immune landscape, amplify the therapeutic effect of other antitumor therapies, and induce immunosensitization of tumors to immunotherapy, shedding new light on the cancer treatment. Tremendous advances in nanotechnology are also expected to bring unprecedented benefits to enhancing the antitumor efficiency and immunological effects of therapeutic US, as well as therapeutic US‐derived bimodal and multimodal synergistic therapies. This comprehensive review summarizes the immunological effects induced by different therapeutic US technologies, including ultrasound‐mediated micro‐/nanobubble destruction (UTMD/UTND), sonodynamic therapy (SDT), and focused ultrasound (FUS), as well as the main underlying mechanisms involved. It is also discussed that the recent research progress of engineering intelligent nanoplatform in improving the antitumor efficiency of therapeutic US technologies. Finally, focusing on clinical translation, the key issues and challenges currently faced are summarized, and the prospects for promoting the clinical translation of these emerging nanomaterials and ultrasonic immunotherapy in the future are proposed.
This comprehensive review summarizes the immunological effects induced by different therapeutic ultrasound technologies, including ultrasound‐mediated microbubble destruction (UTMD), sonodynamic therapy (SDT), and focused ultrasound (FUS), as well as the main underlying mechanisms involved.
Humic substances originating from various organic matters can ameliorate soil properties, stimulate plant growth, and improve nutrient uptake. Due to the low calorific heating value, leonardite is ...rather unsuitable as fuel. However, it may serve as a potential source of humic substances. This study was aimed at characterizing the leonardite-based soil amendments and examining the effect of their application on the soil microbial community, as well as on potato growth and tuber yield. A high yield (71.1%) of humic acid (LHA) from leonardite has been demonstrated. Parental leonardite (PL) and LHA were applied to soil prior to potato cultivation. The 16S rRNA sequencing of soil samples revealed distinct relationships between microbial community composition and the application of leonardite-based soil amendments. Potato tubers were planted in pots in greenhouse conditions. The tubers were harvested at the mature stage for the determination of growth and yield parameters. The results demonstrated that the LHA treatments had a significant effect on increasing potato growth (54.9%) and tuber yield (66.4%) when compared to the control. The findings highlight the importance of amending leonardite-based humic products for maintaining the biogeochemical stability of soils, for keeping their healthy microbial community structure, and for increasing the agronomic productivity of potato plants.
Lesch-Nyhan disease (LND) is a rare disorder involving pathogenic variants in the
gene encoding the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) that result in hyperuricemia, ...intellectual disability, dystonic movement disorder, and compulsive self-mutilation. The purpose of the present study was to characterize the genetic basis of LND and describe its phenotypic heterogeneity by identifying the variation in the
gene in a cohort of Chinese LND patients.
The median age at diagnosis was 31 mo (interquartile range (IQR): 7-76 mo), and the initial manifestations were mainly head control weakness and motor development delay. The median age of self-mutilation behavior onset was 19 mo (IQR: 17-24 mo), and all patients were required to travel in a wheelchair and fall into the predicament of compulsive self-harm behavior. There were two patients whose blood uric acid levels were normal for their high urinary acid excretion fraction without taking uric acid-lowering drugs. Seven different pathogenic variants of the
gene were identified among eight independent pedigrees, including four novel mutations c.299 (exon 3) T > A; loss (exon: 6) 84 bp; c.277_281delATTGC; c.468_470delGAT. The pathogenic variant sites were mainly concentrated in exon 3, and truncating mutations (including frameshift mutations and nonsense mutations) were the most common genetic variant types (5/7, 71.4%).
The present study described the phenotypic and molecular spectrum of LND in eight Chinese families, including four novel mutations, which expands our understanding of LND.
Pancreatic cancer (PaC) consists of a bulk of stroma cells which contribute to tumor progression by releasing angiogenic factors. Recent studies have found that periostin (POSTN) is closely associate ...with the metastatic potential and prognosis of PaC. The purpose of this study is to determine the role of POSTN in tumor angiogenesis and explore the precise mechanisms. In this study, we used lentiviral shRNA and human recombinant POSTN protein (rPOSTN) to negatively and positively regulate POSTN expression in vitro. We found that increased POSTN expression promoted the tubule formation dependent on human umbilical vein endothelial cells (HUVECs). Moreover, knockdown of POSTN in PaC cells reduced tumor growth and VEGF expression in vivo. In accordance with these observations, we found that Erk phosphorylation and its downstream VEGF expression were upregulated achieved in rPOSTN-treated groups, opposing results were obversed in POSTN-slienced group. Meanwhile, Erk inhibitor SCH772984 significantly decreased VEGF expression as well as tubule formation of HUVECs in rPOSTN-treated PaC cells. Taken together, these findings suggest that POSTN promotes tumor angiogenesis via Erk/VEGF signaling in PaC and POSTN may be a new target for cancer anti-vascular treatment.
As researchers globally work towards a fully digital representation of the earth and its processes - i.e. a true Digital Earth - the need grows for software and systems to link disparate computer ...simulation models of various parts of the earth in a reliable and highly functional way. Web services have been demonstrated as an effective way to share and reuse models as they enable communication and interoperation among applications via the Internet. However, even using well-designed software tools, it remains a daunting process to publish heterogeneous environmental models as web services and provide long-term maintenance in response to changing computational environments. We present an approach that enables environmental models to be published as long-term functional web services on the same platform regardless of execution mode, programming language, and computational environment conflicts. The approach adopts the OpenGMS Wrapper System (OGMS-WS) for service publishing and Docker containers for model isolation. A streamflow prediction service is developed using this approach and is applied to analyze historical streamflow trends in Bangladesh. We demonstrate that this approach can lower the barrier to deploying heterogeneous environmental models as long-term functional web services, contributing to the development of a Digital Earth.
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