Transcriptome analysis reveals the mechanism for blue-light-induced biosynthesis of delphinidin derivatives in harvested purple pepper fruit.

Anthocyanins are the main pigments that affect the color and quality of purple-fruited sweet pepper (Capsicum annuum). Our previous study indicated that blue light can induce anthocyanin accumulation in purple pepper. In view of its underlying mechanism that is unclear, here, anthocyanin content was determined, and transcriptome analysis was performed on pepper fruits harvested from different light treatments. As a result, among the identified anthocyanin metabolites, the levels of delphinidin (Dp) glycosides, including Dp-3-O-rhamnoside, Dp-3-O-rutinoside, and Dp-3-O-glucoside, were highly accumulated in blue-light-treated fruit, which are mainly responsible for the appearance color of purple pepper. Correlation between anthocyanin content and transcriptomic analysis indicated a total of 1,619 upregulated genes were found, of which six structural and 12 transcription factor (TF) genes were involved in the anthocyanin biosynthetic pathway. Structural gene, for instance, CaUFGT as well as TFs such as CaMYC2-like and CaERF113, which were highly expressed under blue light and presented similar expression patterns consistent with Dp glycoside accumulation, may be candidate genes for anthocyanin synthesis in response to blue-light signal.

Pharmacological EZH2 inhibition combined with retinoic acid treatment promotes differentiation and apoptosis in rhabdomyosarcoma cells.

BACKGROUND: Rhabdomyosarcomas (RMS) are predominantly paediatric sarcomas thought to originate from muscle precursor cells due to impaired myogenic differentiation. Despite intensive treatment, 5-year survival for patients with advanced disease remains low (< 30%), highlighting a need for novel therapies to improve outcomes. Differentiation therapeutics are agents that induce differentiation of cancer cells from malignant to benign. The histone methyltransferase, Enhancer of Zeste Homolog 2 (EZH2) suppresses normal skeletal muscle differentiation and is highly expressed in RMS tumours. RESULTS: We demonstrate combining inhibition of the epigenetic modulator EZH2 with the differentiating agent retinoic acid (RA) is more effective at reducing cell proliferation in RMS cell lines than single agents alone. In PAX3-FOXO1 positive RMS cells this is due to an RA-driven induction of the interferon pathway resulting in apoptosis. In fusion negative RMS, combination therapy led to an EZH2i-driven upregulation of myogenic signalling resulting in differentiation. In both subtypes, EZH2 is significantly associated with enrichment of trimethylated lysine 27 on histone 3 (H3K27me3) in genes that are downregulated in untreated RMS cells and upregulated with EZH2 inhibitor treatment. These results provide insight into the mechanism that drives the anti-cancer effect of the EZH2/RA single agent and combination treatment and indicate that the reduction of EZH2 activity combined with the induction of RA signalling represents a potential novel therapeutic strategy to treat both subtypes of RMS. CONCLUSIONS: The results of this study demonstrate the potential utility of combining EZH2 inhibitors with differentiation agents for the treatment of paediatric rhabdomyosarcomas. As EZH2 inhibitors are currently undergoing clinical trials for adult and paediatric solid tumours and retinoic acid differentiation agents are already in clinical use this presents a readily translatable potential therapeutic strategy. Moreover, as inhibition of EZH2 in the poor prognosis FPRMS subtype results in an inflammatory response, it is conceivable that this strategy may also synergise with immunotherapies for a more effective treatment in these patients.

A Novel Variant of Avian Reovirus Is Pathogenic to Vaccinated Chickens.

Avian reovirus (ARV) infections, characterized by severe arthritis, tenosynovitis, pericarditis, and poor weight gain, have become increasingly serious in recent years. The economic impact is significant as it causes growth inhibition and immunosuppression. Some commercial poultry in China have been widely vaccinated with available ARV vaccines; however, infections continue to occur even after vaccination. This study aimed to isolate a novel variant, ARV-SD19/11103, from the joint tissues of infected broiler chickens vaccinated with ARV vaccines in Shandong Province. Genetic evolution analysis of the major protective antigen σC gene in ARVs showed that ARV-SD19/11103 was located in the genotype cluster I but not in the same sub-cluster as the S1133 vaccine strain. The amino acid sequence similarity between SD19/11103 and vaccine strains S1133, 1733, and 2408 was <80%. After analyzing the amino acid sequences of the σC protein, 33 amino acid differences were found between the new variant isolate and the vaccine strains. This novel variant showed obvious pathogenicity in specific pathogen-free chicken embryos and chicks and could cause serious disease in chickens vaccinated with commercially available ARV vaccines. Cross-neutralization experiments further demonstrated a significant antigenic difference between the novel variant and genotype cluster I ARV strains. The novel variant strain isolated in this study provides an important theoretical basis for understanding the prevalence and genetic evolutionary characteristics of ARV variant strains in our country. This study identified the causes of ARVs circulating and emphasizes the needs for developing new vaccines against novel ARV variants.

Review: Targeting EZH2 in neuroblastoma.

Neuroblastoma is one of the commonest extra-cranial pediatric tumors, and accounts for over 15% of all childhood cancer mortality. Risk stratification for children with neuroblastoma is based on age, stage, histology, and tumor cytogenetics. The majority of patients are considered to have high-risk neuroblastoma, for which the long-term survival is less than 50%. Current treatments combine surgical resection, chemotherapy, stem cell transplantation, radiotherapy, anti-GD2 based immunotherapy as well as the differentiating agent isotretinoin. Despite the intensive multimodal therapies applied, there are high relapse rates, and recurrent disease is often resistant to further therapy. Enhancer of Zeste Homolog 2 (EZH2), a catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is a histone methyltransferase that represses transcription through trimethylation of lysine residue K27 on histone H3 (H3K27me3). It is responsible for epigenetic repression of transcription, making EZH2 an essential regulator for cell differentiation. Overexpression of EZH2 has been shown to promote tumorigenesis, cancer cell proliferation and prevent tumor cells from differentiating in a number of cancers. Therefore, research has been ongoing for the past decade, developing treatments that target EZH2 in neuroblastoma. This review summarises the role of EZH2 in neuroblastoma and evaluates the latest research findings on the therapeutic potential of targeting EZH2 in the treatment of neuroblastoma.

Chromosome-level genome assembly and annotation of the prickly nightshade Solanum rostratum Dunal.

The prickly nightshade Solanum rostratum, an annual malignant weed, is native to North America and has globally invaded 34 countries, causing serious threats to ecosystems, agriculture, animal husbandry, and human health. In this study, we constructed a chromosome-level genome assembly and annotation of S. rostratum. The contig-level genome was initially assembled in 898.42 Mb with a contig N50 of 62.00 Mb from PacBio high-fidelity reads. With Hi-C sequencing data scaffolding, 96.80% of the initially assembled sequences were anchored and orientated onto 12 pseudo-chromosomes, generating a genome of 869.69 Mb with a contig N50 of 72.15 Mb. We identified 649.92 Mb (72.26%) of repetitive sequences and 3,588 non-coding RNAs in the genome. A total of 29,694 protein-coding genes were predicted, with 28,154 (94.81%) functionally annotated genes. We found 99.5% and 91.3% complete embryophyta_odb10 genes in the pseudo-chromosomes genome and predicted gene datasets by BUSCO assessment. The present genomic resource provides essential information for subsequent research on the mechanisms of environmental adaptation of S. rostratum and host shift in Colorado potato beetles.

Asymmetric Swelling Behaviors of High-Energy-Density Lithium-Ion Batteries with a SiOx /Graphite Composite Anode.

The battery swelling originated from the electrode swelling is a big obstacle for the practical application of high-energy-density lithium-ion batteries (HED-LIBs). Herein, the HED-LIBs are constructed by SiOx /graphite composite anode and LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) cathode and their swelling behaviors are investigated at the cell, electrode, and particle scales. there are three expansion stages during the charging while one expansion followed by two contraction stages during the discharging process. The expansion ratio is in direct proportion to the ratio of SiOx content and about 10 times larger than that of the cathode. A 100 nm thick double-layer solid electrolyte interface, comprises LiF, Li2 O, and Li2 CO3 , forms on the surface of the SiOx particles, and evolves into a 300 nm thick triple-layer after cycling. The performance degradation of HED-LIBs is associated with the expansion of anodes, increase in resistance, and consumption of Li in the anodes during cycling. This study is expected to guide the future selection and design of HED-LIBs and battery packs.

Iris lactea var. chinensis plant drought tolerance depends on the response of proline metabolism, transcription factors, transporters and the ROS-scavenging system.

BACKGROUND: Iris lactea var. chinensis, a perennial herbaceous species, is widely distributed and has good drought tolerance traits. However, there is little information in public databases concerning this herb, so it is difficult to understand the mechanism underlying its drought tolerance. RESULTS: In this study, we used Illumina sequencing technology to conduct an RNA sequencing (RNA-seq) analysis of I. lactea var. chinensis plants under water-stressed conditions and rehydration to explore the potential mechanisms involved in plant drought tolerance. The resulting de novo assembled transcriptome revealed 126,979 unigenes, of which 44,247 were successfully annotated. Among these, 1187 differentially expressed genes (DEGs) were identified from a comparison of the water-stressed treatment and the control (CK) treatment (T/CK); there were 481 upregulated genes and 706 downregulated genes. Additionally, 275 DEGs were identified in the comparison of the rehydration treatment and the water-stressed treatment (R/T). Based on Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) analysis, the expression levels of eight randomly selected unigenes were consistent with the transcriptomic data under water-stressed and rehydration treatment, as well as in the CK. According to Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, proline metabolism-related DEGs, including those involved in the 'proline catabolic process', the 'proline metabolic process', and 'arginine and proline metabolism', may play important roles in plant drought tolerance. Additionally, these DEGs encoded 43 transcription factors (TFs), 46 transporters, and 22 reactive oxygen species (ROS)-scavenging system-related proteins. Biochemical analysis and histochemical detection showed that proline and ROS were accumulated under water-stressed conditions, which is consistent with the result of the transcriptomic analysis. CONCLUSIONS: In summary, our transcriptomic data revealed that the drought tolerance of I. lactea var. chinensis depends on proline metabolism, the action of TFs and transporters, and a strong ROS-scavenging system. The related genes found in this study could help us understand the mechanisms underlying the drought tolerance of I. lactea var. chinensis.

Unlocking Charge Transfer Limitations for Extreme Fast Charging of Li-Ion Batteries.

Extreme fast charging (XFC) of high-energy Li-ion batteries is a key enabler of electrified transportation. While previous studies mainly focused on improving Li ion mass transport in electrodes and electrolytes, the limitations of charge transfer across electrode-electrolyte interfaces remain underexplored. Herein we unravel how charge transfer kinetics dictates the fast rechargeability of Li-ion cells. Li ion transfer across the cathode-electrolyte interface is found to be rate-limiting during XFC, but the charge transfer energy barrier at both the cathode and anode have to be reduced simultaneously to prevent Li plating, which is achieved through electrolyte engineering. By unlocking charge transfer limitations, 184 Wh kg-1 pouch cells demonstrate stable XFC (10-min charge to 80 %) which is otherwise unachievable, and the lifetime of 245 Wh kg-1 21700 cells is quintupled during fast charging (25-min charge to 80 %).

Which aerosol type dominate the impact of aerosols on ozone via changing photolysis rates?

The impact of aerosols on ozone via influencing photolysis rates is a combined effect of absorbing aerosols (AA) and scattering aerosols (SA). However, AA and SA show different optical properties and influence photolysis rates differently, which then cause different impacts on ozone. Till now, the dominate factor is disconfirmed, which is largely due to the impact of SA on ozone not reaching to a consistent conclusion. In this study, the WRF-Chem model was implemented to simulate the air pollutants over the North China Plain (NCP). The impacts of AA and SA on ozone via influencing photolysis rates were quantitatively isolated and analyzed. Our results also demonstrated the decreasing effect of AA on ozone within planet boundary layer (PBL) which is consistent with the conclusions of previous studies. But for SA, it decreased the ozone chemical contribution (CHEM) near surface but increased which in the upper layers of PBL, that enlarge the ozone vertical gradients. In this case, more vertical exchanges of ozone would occur with the effect of vertical mixing motion of atmosphere, then the opposite CHEM variations were counteracted with each other and finally led to very slight changes in ozone within PBL. Thus, it can be summarized that AA dominate this impact of aerosols on ozone. Reducing AA could cause a general increase in ozone (ΔO3) over the NCP. Based on the aerosol levels of this case, ΔO3 would be seen over 86 % of the areas in the NCP when reducing AA by 3/4 and ΔO3 was more significant in the megacities. Our study highlights the different relationships between ozone and aerosol types, which suggests that more attentions should be paid on aerosol types, especially AA, when making the synergetic control strategy of aerosols and ozone in China.

Knockdown of GFAT disrupts chitin synthesis in Hyphantria cunea larvae.

Glutamine-fructose-6-phosphate transaminase (GFAT) has been reported to regulate the hexosamine biosynthetic pathway as the first rate-limiting enzyme. As a key enzyme that catalyzes the substrate of glycosylation modification, which has a wide-ranging effect on cellular functions. However, there are few studies on the relationship between GFAT and chitin metabolism in insects. In the present study, the GFAT gene from Hyphantria cunea was identified based on transcriptome and bioinformatic analysis. The role of HcGFAT in regulating development and chitin synthesis was analyzed by RNA interference (RNAi) in H. cunea larvae. The full-length HcGFAT gene (2028 bp) encodes a 676 amino acid (aa) polypeptide had typical structural features of the SIS and Gn_AT_II superfamily. Phylogenetic analyses showed that GFAT of H. cunea shares the highest homology and identity with GFAT of Ostrinia furnacalis. Expression profiles indicated that HcGFAT was expressed throughout larval, pupal and three tissues (midgut, fat body, epidermis), and highly expressed in the last instar of larvae and strongly expressed in epidermis among three tissues. Bioassay results showed that knockdown of HcGFAT repressed larval growth and development, resulting in a significant loss of larval body weight. Meanwhile, HcGFAT knockdown also significantly caused larval developmental deformity. Knockdown of HcGFAT regulated the expression of four other critical genes in the chitin synthesis pathway (HcGNA, HcPAGM, HcUAP, HcCHSA), and ultimately resulted in decreased chitin content in the epidermis. In summary, these findings indicated that GFAT plays a critical role in larval growth and development, as well as chitin synthesis in H. cunea.

Structural Characterization of the Acer ukurunduense Chloroplast Genome Relative to Related Species in the Acer Genus.

Acer ukurunduense refers to a deciduous tree distributed in Northeast Asia and is a widely used landscaping tree species. Although several studies have been conducted on the species' ecological and economic significance, limited information is available on its phylo-genomics. Our study newly constitutes the complete chloroplast genome of A. ukurunduense into a 156,645-bp circular DNA, which displayed a typical quadripartite structure. In addition, 133 genes were identified, containing 88 protein-coding genes, 37 tRNA genes, and eight rRNA genes. In total, 107 simple sequence repeats and 49 repetitive sequences were observed. Thirty-two codons indicated that biased usages were estimated across 20 protein-coding genes (CDS) in A. ukurunduense. Four hotspot regions (trnK-UUU/rps16, ndhF/rpl32, rpl32/trnL-UAG, and ycf1) were detected among the five analyzed Acer species. Those hotspot regions may be useful molecular markers and contribute to future population genetics studies. The phylogenetic analysis demonstrated that A. ukurunduense is most closely associated with the species of Sect. Palmata. A. ukurunduense and A. pubipetiolatum var. pingpienense diverged in 22.11 Mya. We selected one of the hypervariable regions (trnK-UUU/rps16) to develop a new molecular marker and designed primers and confirmed that the molecular markers could accurately discriminate five Acer species through Sanger sequencing. By sequencing the cp genome of A. ukurunduense and comparing it with the relative species of Acer, we can effectively address the phylogenetic problems of Acer at the species level and provide insights into future research on population genetics and genetic diversity.

Source apportionments of black carbon induced by local and regional transport in the atmospheric boundary layer of the Yangtze River Delta under stable weather conditions.

Long-range transport (LRT) and local accumulation (LA) are key atmospheric physical processes affecting air pollution formation, and their impacts on surface air pollution have been extensively researched. Due to the lack of vertical observations and emphases on model simulations, the characteristics and regional sources of black carbon (BC) aerosol profiles have been relatively understudied. In this study, the chemistry-coupled Weather Research and Forecasting model (WRF-Chem) with a BC source-tagging method was used to quantify BC source contributions (considering 18 geographical regions over east Asia, including 3 subregions over the Yangtze River Delta (YRD)) during a November 2017 pollution event in the YRD, China. In this event, the YRD mainly experienced a uniform pressure field, stable weather and weak wind fields. During the uniform high-pressure period, the dominant contribution to surface BC in each sub-region was from that region itself (70.6 %-98.2 %), with little intra- and inter-regional transport. During the uniform low-pressure period, highly variable contributions to the surface BC from intra-regional transport within the YRD (0.05 %-65.9 %) and inter-regional transport outside the YRD (mostly from Anhui (AH) to the west of the YRD, 0.37 %-23.9 %) were simulated. In the vertical direction, the dominant contributors were local YRD sources (73.8 %-94.2 %) below the atmospheric boundary layer (ABL). The inter-transport contributions increased extensively above the ABL. As a westerly trough crossing, a long-range inter-regional transport from South China (SCHN, 3.3 %) and the North China Plain (NCP, 2.7 %) was simulated above the ABL. We found that when the surface experienced similar stable weather conditions, the weather conditions in the upper air may have been quite different, resulting in significant differences in the regional transport of BC in the upper ABL. This study provides a reference for improving air quality from the local scale to the regional scale.

The impact of the aerosol reduction on the worsening ozone pollution over the Beijing-Tianjin-Hebei region via influencing photolysis rates.

Due to the implementation of the toughest-ever emission control actions across China from 2013 to present, the aerosols are decreasing annually but ozone is simultaneously increasing, especially over the Beijing-Tianjin-Hebei (BTH) region, where ozone pollution can even spread into winter. Quantifying each impact of aerosols on ozone in all seasons is urgent for the worsening ozone pollution in the improved aerosol air quality. In this study, we focused on the impact of aerosols on ozone via influencing photolysis rates. The air pollutants were simulated over the Central East China (CEC) in 2018 by using the Weather Research and Forecasting with Chemistry (WRF-Chem) model. By implementing emissions with base years of 2014 and 2018, we quantified the increase in ozone (ΔOzone_photolysis) caused by the decreasing aerosol concentrations (ΔPM2.5) by influencing photolysis rates over the BTH region in all seasons. Furthermore, combined with the ozone observations, the contribution of ΔOzone_photolysis to the total changes in ozone (ΔOzone_total) in all seasons was quantitatively discussed. Our results showed that ΔPM2.5 showed obvious seasonal variations, which PM2.5 decreased more significantly in winter and autumn than in spring and summer, although significant reductions in anthropogenic emissions were observed in all seasons. Consistent seasonal variations were also observed in ΔOzone_photolysis, and the mean increases reached 5.5 µg m-3, 2.6 µg m-3, 1.2 µg m-3, and 1.4 µg m-3 in winter, autumn, spring, spring, and summer, respectively. Compared with ΔOzone_total, ΔOzone_photolysis accounted for 36.3%, 17.2%, 3.5% and 10.6% of ΔOzone_total in winter, autumn, spring, and summer, respectively, suggesting that ΔOzone_photolysis was not the primary contributor to the current changes in ozone over the BTH region. However, the 36.3% contribution to ΔOzone_total in winter suggested that ΔOzone_photolysis is still an important contributor and should not be ignored when discussing the formation of high ozone episodes occurring in winter.

Vertical evolution of black and brown carbon during pollution events over North China Plain.

The vertical distribution of carbonaceous aerosol impacts climate change, air quality and human health, but there is a lack of in-situ vertical observations of black (BC) and brown carbon (BrC). Thus, the characteristic of vertical profiles of BC concentration, particle number concentration (PNC), O3 concentration and optical absorption of BC and BrC were observed in a suburban site over North China Plain, where heavy pollution of PM2.5 and O3 always occurred in winter and summer, respectively. In winter, during a heavy pollution episode, the BC and PNC was near uniformly distributed within mixing layer (ML) (15.2 ± 6.7 µg m-3 and 678 ± 227 p cm-3, respectively) and decreased with altitude above the ML. The BC heating rate reached about 0.13 K h-1 during the heaviest pollution day. In summer, the BC concentration (2.9 ± 1.3 µg m-3) in ML during the middle O3 pollution events was higher than that (1.7 ± 0.6 µg m-3) during the light O3 pollution. The light absorption coefficients of BC at 880 nm and BrC at 375 nm measured in the early morning were lower than that in the daytime, and the contribution of BrC to total light absorption of carbonaceous aerosols was in the range of 27-47%. In addition, BC was effectively transported to high altitude than BrC in the daytime. The light absorption of secondary BrC in the daytime was higher 10-20% than that in the early morning. Simultaneously, the contribution of secondary BrC to the total BrC light absorption at 375 nm was range from 32% to 68% within 1000 m.

A single microbubble formulation carrying 5-fluorouridine, Irinotecan and oxaliplatin to enable FOLFIRINOX treatment of pancreatic and colon cancer using ultrasound targeted microbubble destruction.

FOLFIRINOX and FOLFOXIRI are combination chemotherapy treatments that incorporate the same drug cocktail (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) but exploit an altered dosing regimen when used in the management of pancreatic and colorectal cancer, respectively. Both have proven effective in extending life when used to treat patients with metastatic disease but are accompanied by significant adverse effects. To facilitate improved tumour-targeting of this drug combination, an ultrasound responsive microbubble formulation loaded with 5-fluorouridine, irinotecan and oxaliplatin (FIRINOX MB) was developed and its efficacy tested, together with the non-toxic folinic acid, in preclinical murine models of pancreatic and colorectal cancer. A significant improvement in tumour growth delay was observed in both models following ultrasound targeted microbubble destruction (UTMD) mediated FIRINOX treatment with pancreatic tumours 189% and colorectal tumours 82% smaller at the conclusion of the study when compared to animals treated with a standard dose of FOLFIRINOX. Survival prospects were also improved for animals in the UTMD mediated FIRINOX treatment group with an average survival of 22.17 ± 12.19 days (pancreatic) and 44.40 ± 3.85 days (colorectal) compared to standard FOLFIRINOX treatment (15.83 ± 4.17 days(pancreatic) and 37.50 ± 7.72 days (colon)). Notably, this improved efficacy was achieved using FIRINOX MB that contained 5-fluorouricil, irinotecan and oxaliplatin loadings that were 13.44-fold, 9.19-fold and 1.53-fold lower than used for the standard FOLFIRINOX treatment. These results suggest that UTMD enhances delivery of FIRINOX chemotherapy, making it significantly more effective at a substantially lower dose. In addition, the reduced systemic levels of 5-fluorouracil, irinotecan and oxaliplatin should also make the treatment more tolerable and reduce the adverse effects often associated with this treatment.

[Variation Characteristics and Source Analysis of Carbonaceous Aerosols in Winter in Jiashan].

Organic carbon (OC), elemental carbon (EC), and PM2.5 concentration data obtained from Shanxi Super Station in Jiashan County of Jiaxing City, in the winter of 2018 and 2019, were analyzed to determine the variation and potential source areas of carbonaceous aerosols. The results show that OC concentrations in the winter of 2018 and 2019 were 6.90 µg·m-3 and 5.63 µg·m-3, respectively, while EC concentrations were 2.47 µg·m-3 and 1.57 µg·m-3, respectively. The concentrations of OC and EC in the winter of 2019 were lower than those in the winter of 2018, by approximately 18.4% and 36.4%, respectively. In 2018 and 2019, the concentrations of secondary organic carbon (SOC), calculated using the minimum R-squared (MRS) method, were 1.49 µg·m-3 and 1.97 µg·m-3, respectively, and the concentrations of primary organic carbon (POC) were 5.41 µg·m-3 and 3.66 µg·m-3, respectively. The proportion of POC in OC showed a downward trend, from 96.0% in December 2018 to 64.9% in February 2020, indicating a decrease of 31.1 percentage points. SOC showed an upward trend, increasing by 31.1 percentage points from 4.0% in December 2018 to 35.1% in February 2020. It is worth noting that with the increase in PM2.5 concentration, the concentration of OC and EC increased by 474.7% and 408.2%, respectively, although the proportion of OC in PM2.5 decreased from 18.8% to 12.3%. and the percentage of OC decreased from 5.8% to 3.3%. The contribution of POC to PM2.5 did not fluctuate, and only decreased significantly above 150 µg·m-3, while the contribution of SOC to PM2.5 first decreased and then increased. In Jiaxing, the potential sources of OC and EC were mainly southern Jiangsu, southeastern Anhui, local Jiaxing, and northern Zhejiang. In the winter of the contribution concentrations of OC and EC in the main potential source regions were approximately 2 µg·m-3 and 6 µg·m-3 lower, respectively, than in winter 2018. The range of high values in the potential source regions also decreased in 2019. Before the COVID-19 epidemic, it was affected by both motor vehicle exhaust emissions and coal burning. During the Spring Festival and home isolation, due to traffic control and other reasons, motor vehicle emissions were reduced, which leaving coal burning as the main contributor.

Sonodynamic therapy complements PD-L1 immune checkpoint inhibition in a murine model of pancreatic cancer.

The emergence of immune checkpoint inhibitors (ICI's) in the past decade has proven transformative in the area of immuno-oncology. The PD-1/PD-L1 axis has been particularly well studied and monoclonal antibodies developed to block either the receptor (anti PD-1) or its associated ligand (anti PD-L1) can generate potent anti-tumour immunity in certain tumour models. However, many "immune cold" tumours remain unresponsive to ICI's and strategies to stimulate the adaptive immune system and make these tumours more susceptible to ICI treatment are currently under investigation. Sonodynamic therapy (SDT) is a targeted anti-cancer treatment that uses ultrasound to activate a sensitiser with the resulting generation of reactive oxygen species (ROS) causing direct cell death by apoptosis and necrosis. SDT has also been shown to stimulate the adaptive immune system in a pre-clinical model of colorectal cancer. In this manuscript, we investigate the ability of microbubble mediated SDT to control tumour growth in a bilateral tumour mouse model of pancreatic cancer by treating the target tumour with SDT and observing the effects at the off-target untreated tumour. The results demonstrated a significant 287% decrease in tumour volume when compared to untreated animals 11 days following the initial treatment with SDT, which reduced further to 369% when SDT was combined with anti-PD-L1 ICI treatment. Analysis of residual tumour tissues remaining after treatment revealed increased levels of infiltrating CD4+ and CD8+ T-lymphocytes (respectively 4.65 and 3.16-fold more) in the off-target tumours of animals where the target tumour was treated with SDT and anti-PD-L1, when compared to untreated tumours. These results suggest that SDT treatment elicits an adaptive immune response that is potentiated by the anti-PD-L1 ICI in this particular model of pancreatic cancer.

Synthesis of a gemcitabine-modified phospholipid and its subsequent incorporation into a single microbubble formulation loaded with paclitaxel for the treatment of pancreatic cancer using ultrasound-targeted microbubble destruction.

Gemcitabine and nab-paclitaxel (Abraxane®) is a standard of care chemotherapy combination used in the treatment of patients with advanced pancreatic cancer. While the combination has shown a survival benefit when compared to gemcitabine monotherapy, it is associated with significant off-target toxicity. Ultrasound targeted microbubble destruction (UTMD) has emerged as an effective strategy for the site-specific deposition of drug-payloads. However, loading a single microbubble formulation with two drug payloads can be challenging and often involves several manipulations post-microbubble preparation that can be cumbersome and generally results in low / inconsistent drug loadings. In this manuscript, we report the one-pot synthesis of a gemcitabine functionalised phospholipid and use it to successfully generate stable microbubble formulations loaded with gemcitabine (Lipid-Gem MB) or a combination of gemcitabine and paclitaxel (Lipid-Gem-PTX MB). Efficacy of the Lipid-Gem MB and Lipid-Gem-PTX MB formulations, following ultrasound (US) stimulation, was evaluated in a three-dimensional (3D) PANC-1 spheroid model of pancreatic cancer and a mouse model bearing ectopic BxPC-3 tumours. The results demonstrated a significant reduction in the cell viability in spheroids for both formulations reducing from 90 ± 10% to 62 ± 5% for Lipid-Gem MB and 84 ± 10% to 30 ± 6% Lipid-Gem-PTX MB following US irradiation. When compared with a clinically relevant dose of free gemcitabine and paclitaxel (i.e. non-particle bound) in a BxPC-3 murine pancreatic tumour model, both formulations also improved tumour growth delay with tumours 40 ± 20% and 40 ± 30% smaller than the respective free drug formulation when treated with Lipid-Gem MB and Lipid-Gem-PTX MB respectively, at the conclusion of the experiment. These results highlight the potential of UTMD mediated Gem / PTX as a treatment for pancreatic cancer and the facile preparation of Lipid-Gem-PTX MBs using a gemcitabine functionalised lipid should expedite clinical translation of this technology.

A rapid antimicrobial photodynamic water treatment strategy utilizing a xanthene dye with subsequent removal by Goethite Nanoparticles.

Although widely accepted as a water sterilisation technique, chlorination results in the production of potentially harmful by-products, mainly Trihalomethanes. Furthermore, the chlorination process requires specialised infrastructure, management and high costs. In this research paper a potential alternative sterilisation technique was investigated. This rapid three-step process utilized Goethite Nanoparticles and the photosensitising capabilities of a xanthene dye. Rose Bengal (RB) a compound primarily used as a stain to diagnose damaged tissue in the eye was utilized under visible light excitation to sterilise water containing gram-positive Staphylococcus aureus and Bacillus cereus. Bacterial reductions (cfu/ml) of up to 6log10 are reported at RB concentrations of 0.5 mg/L and 10 mg/L for S. aureus and B. cereus, respectively. Goethite Nanoparticles (GNP's), an iron oxyhydroxide, were synthesised by co-precipitation of iron salts and used to adsorb RB post-sterilisation. Poly-vinyl Alcohol (PVA) functionalised GNP's were synthesised to highlight the adsorbent capabilities of the GNP surface. The adsorption capacity for uncoated GNPs was 476.19 mg/g, this reduced to 170.4 mg/g for PVA-GNP's, highlighting the highly porous nature of the synthesised GNP surface. Adsorption was optimal in slightly acidic conditions (pH5-6). The adsorption parameters best followed Lagergens Pseudo-second order kinetics with correlation coefficients close to unity. At the highest envisaged RB concentration (10 mg/L) approximately 20 mg/L GNP's was required to remove the dye from solution post-treatment. Flame Atomic Absorption analysis of the water post-removal revealed Iron concentrations of 0.058 mg/L. This correlates to removal efficacy of 99.71% with residual iron levels below the EU recommended limit of 0.2 mg/L.

Mid-infrared electro-optic modulator based on a graphene-embedded plasmonic rib waveguide with ultrahigh electro-optic wavelength tuning.

A graphene-embedded plasmonic rib waveguide (GEPRW) is designed for the mid-infrared electro-optic modulator. The mode characteristics and electro-optic (EO) modulation performances are simulated and optimized by using the finite element method. The results show that propagation length of 103mm and figure of merit of 106 are obtained by adjusting the bias voltage applied to the GEPRW. The EO wavelength tunings are -66.69 and -78.87nm/V for peak L and peak R in the loss spectra when w=3µm and h1=2µm. For a 100 µm long GEPRW, the modulation depths of ∼96.4,∼97.1,∼93.7, and ∼94.9%, and FWHMs of ∼30,∼74,∼34, and ∼59nm can be achieved when λ=1.55, 1.87. 1.89, and 2.23 µm. The EO modulator based on the GEPRW has a wide wavelength tuning range from 1.05 to 2.23 µm. It has high modulation depth, low insertion loss, and broad bandwidth, which can be used as EO tunable devices such as optical interconnects and optical switches.