Treatment of pharmaceutical industry wastewater for water reuse in Jordan using hybrid constructed wetlands.

Developing cost-efficient wastewater treatment technologies for safe reuse is essential, especially in developing countries simultaneously facing water scarcity. This study developed and evaluated a hybrid constructed wetlands (CWs) approach, incorporating tidal flow (TF) operation and utilising local Jordanian zeolite as a wetland substrate for real pharmaceutical industry wastewater treatment. Over 273 days of continuous monitoring, the results revealed that the first-stage TFCWs filled with either raw or modified zeolite performed significantly higher reductions in Chemical Oxygen Demand (COD, 58 %-60 %), Total Nitrogen (TN, 32 %-37 %), and Phosphate (PO4, 46 %-64 %) compared to TFCWs filled with normal sand. Water quality further improved after the second stage of horizontal subsurface flow CWs treatment, achieving log removals of 1.09-2.47 for total coliform and 1.89-2.09 for E. coli. With influent pharmaceutical concentrations ranging from 275 to 2000 µg/L, the zeolite-filled hybrid CWs achieved complete removal (>98 %) for ciprofloxacin, ofloxacin, erythromycin, and enrofloxacin, moderate removal (43 %-81 %) for flumequine and lincomycin, and limited removal (<8 %) for carbamazepine and diclofenac. The overall accumulation of pharmaceuticals in plant tissue and substrate adsorption accounted for only 2.3 % and 4.3 %, respectively, of the total mass removal. Biodegradation of these pharmaceuticals (up to 61 %) through microbial-mediated processes or within plant tissues was identified as the key removal pathway. For both conventional pollutants and pharmaceuticals, modified zeolite wetland media could only slightly enhance treatment without a significant difference between the two treatment groups. The final effluent from all hybrid CWs complied with Jordanian treated industry wastewater reuse standards (category III), and systems filled with raw or modified zeolite achieved over 95 % of samples meeting the highest water reuse category I. This study provides evidence of using hybrid CWs technology as a nature-based solution to address water safety and scarcity challenges.

Immediate postpartum cessation of tenofovir did not increase risk of virological or clinical relapse in highly viremic pregnant mothers with chronic hepatitis B infection.

Background & Aims: Peripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) is the standard of care to prevent mother-to-child transmission of chronic hepatitis B (CHB) infection in mothers who are highly viremic. We investigated the maternal and infant outcomes in a large Chinese cohort of TDF-treated CHB pregnant participants. Methods: In this prospective study, treatment-naive mothers with CHB and highly viremic (HBV DNA ≥200,000 IU/ml) but without cirrhosis were treated with TDF at 24-28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped at delivery or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase were monitored every 6-8 weeks to determine virological relapse (VR). Infants received standard neonatal immunization, and HBV serology was checked at 7-12 months of age. Results: Among 330 participants recruited (median age 30, 82.7% HBeAg+, median HBV DNA 7.82 log IU/ml), TDF was stopped at delivery in 66.4% and at ≥4 weeks in 33.6%. VR was observed in 98.3%, among which 11.6% were retreated with TDF. Timing of TDF cessation did not alter the risk of VR (99.0 vs. 96.9%), clinical relapse (19.5 vs. 14.3%), or retreatment (12.6 vs. 10.1%) (all p > 0.05). A similar proportion of patients developed alanine aminotransferase flare five times (1.1 vs. 2.1%; p = 0.464) and 10 times (0.5 vs. 0%; p = 0.669) above the upper limit of normal (ULN) in the early withdrawal and late withdrawal groups, respectively. No infants developed HBsAg-positivity. Conclusions: PP-TDF and neonatal immunization were highly effective in preventing mother-to-child transmission of HBV in mothers who are highly viremic. Timing of cessation of PP-TDF did not affect the risk of VR or retreatment. Impact and Implications: In pregnant mothers with chronic hepatitis B infection who are started on peripartum tenofovir to prevent mother-to-child-transmission (MTCT), the optimal timing for antiviral withdrawal during the postpartum period remains unknown. This prospective study demonstrates that stopping tenofovir immediately at delivery, compared with longer treatment duration of tenofovir, did not lead to an increased risk of virological relapse, retreatment, or transmission of the virus to the baby. Shortening the duration of peripartum antiviral prophylaxis from 12 weeks to immediately after delivery can be considered. The immediate withdrawal of peripartum tenofovir, combined with standard neonatal immunization schemes, is 100% effective in preventing MTCT among pregnant mothers with CHB who are highly viremic, with a high rate of vaccine response in infants.

Constructed wetlands as nature-based solutions in managing per-and poly-fluoroalkyl substances (PFAS): Evidence, mechanisms, and modelling.

Per- and poly-fluoroalkyl substances (PFAS) have emerged as newly regulated micropollutants, characterised by extreme recalcitrance and environmental toxicity. Constructed wetlands (CWs), as a nature-based solution, have gained widespread application in sustainable water and wastewater treatment and offer multiple environmental and societal benefits. Despite CWs potential, knowledge gaps persist in their PFAS removal capacities, associated mechanisms, and modelling of PFAS fate. This study carried out a systematic literature review, supplemented by unpublished experimental data, demonstrating the promise of CWs for PFAS removal from the influents of varying sources and characteristics. Median removal performances of 64, 46, and 0 % were observed in five free water surface (FWS), four horizontal subsurface flow (HF), and 18 vertical flow (VF) wetlands, respectively. PFAS adsorption by the substrate or plant root/rhizosphere was deemed as a key removal mechanism. Nevertheless, the available dataset resulted unsuitable for a quantitative analysis. Data-driven models, including multiple regression models and machine learning-based Artificial Neural Networks (ANN), were employed to predict PFAS removal. These models showed better predictive performance compared to various mechanistic models, which include two adsorption isotherms. The results affirmed that artificial intelligence is an efficient tool for modelling the removal of emerging contaminants with limited knowledge of chemical properties. In summary, this study consolidated evidence supporting the use of CWs for mitigating new legacy PFAS contaminants. Further research, especially long-term monitoring of full-scale CWs treating real wastewater, is crucial to obtain additional data for model development and validation.

Effects of nanobubble water on digestate soaking hydrolysis of rice straw.

This study investigated the performance of combined nanobubble water (NW) and digestate in the soaking hydrolysis process. Two types of NW (CO2NW and O2NW) with digestate were used to soak rice straw for 1, 2, 3, 5, and 7 days. During soaking process, the volatile fatty acids (VFA) concentration in the treatment with O2NW and digestate for 3 days (O2NW-3 d) reached 7179.5 mg-HAc/L. Moreover, the highest specific methane yield (SMY) obtained in this treatment could reach 336.7 NmL/gVS. Although the addition of NW did not significantly increase SMY from digestate soaking, NW could accelerate the rate of methane production and reduce digestion time of T80. The enrichment of Enterobacter in the soaking process was observed when using CO2NW and O2NW as soaking solutions which played important roles in VFA production. This study provides a new insight into environment-friendly enhanced crop straw pretreatment, combining NW and digestate soaking hydrolysis.

Enhanced bioelectroremediation of heavy metal contaminated groundwater through advancing a self-standing cathode.

Hexavalent chromium (Cr(VI)) contamination in groundwater poses a substantial global challenge due to its high toxicity and extensive industrial applications. While the bioelectroremediation of Cr(VI) has attracted huge attention for its eco-friendly attributes, its practical application remains constrained by the hydrogeochemical conditions of groundwater (mainly pH), low electron transfer efficiency, limitations in electrocatalyst synthesis and electrode fabrication. In this study, we developed and investigated the use of N, S co-doped carbon nanofibers (CNFs) integrated on a graphite felt (GF) as a self-standing cathode (NS/CNF-GF) for the comprehensive reduction of Cr(VI) from real contaminated groundwater. The binder free cathode, prepared through electro-polymerization, was employed in a dual-chamber microbial fuel cell (MFC) for the treatment of Cr (VI)-laden real groundwater (40 mg/L) with a pH of 7.4. The electrochemical characterization of the prepared cathode revealed a distinct electroactive surface area, more wettability, facilitating enhanced adsorption and rapid electron transfer, resulting in a commendable Cr(VI) reduction rate of 0.83 mg/L/h. The MFC equipped with NS/CNF-GF demonstrated the lowest charge transfer resistance (Rct) and generated the highest power density (155 ± 0.3 mW/m2) compared to control systems. The favorable electrokinetics for modified cathode led to swift substrate consumption in the anode, releasing more electrons and protons, thereby accelerating Cr(VI) reduction to achieve the highest cathodic coulombic efficiency (C.Eca)of80 ± 1.3 %. A similar temporal trend observed between Cr(VI) removal efficiency, COD removal efficiency, and C.Eca, underscores the effective performance of the modified electrode. The reusability of the binder free cathode, exemption from catholyte preparation and the absence of pH regulation requirements highlighted the potential scalability and applicability of our findings on a larger scale.

DTONet a Lightweight Model for Melanoma Segmentation.

With the further development of neural networks, automatic segmentation techniques for melanoma are becoming increasingly mature, especially under the conditions of abundant hardware resources. This allows for the accuracy of segmentation to be improved by increasing the complexity and computational capacity of the model. However, a new problem arises when it comes to actual applications, as there may not be the high-end hardware available, especially in hospitals and among the general public, who may have limited computing resources. In response to this situation, this paper proposes a lightweight deep learning network that can achieve high segmentation accuracy with minimal resource consumption. We introduce a network called DTONet (double-tailed octave network), which was specifically designed for this purpose. Its computational parameter count is only 30,859, which is 1/256th of the mainstream UNet model. Despite its reduced complexity, DTONet demonstrates superior performance in terms of accuracy, with an IOU improvement over other similar models. To validate the generalization capability of this model, we conducted tests on the PH2 dataset, and the results still outperformed existing models. Therefore, the proposed DTONet network exhibits excellent generalization ability and is sufficiently outstanding.

Processes and mechanisms in remediation of aqueous chromium contamination by sulfidated nano-scale zerovalent iron (S-nZVI): Experimental and computational investigations.

Sulfidated nano-scale zerovalent iron (S-nZVI) has emerged as an advanced functional nanomaterial for efficiently remediating Cr(VI) contamination in aqueous environments. However, there is an insufficient understanding of its coherent process, removal pathway, and hydrochemical reactive mechanisms, presenting potential challenges for its future environmental applications. To address this gap, this study successfully synthesized S-nZVI through a chemical precipitation method and effectively applied it for the removal of Cr(VI). Additional characterization revealed that the removal of Cr(VI) followed a sequence of rapid chemisorption and intraparticle diffusion processes, concomitant with an increase in pH and a decrease in oxidation-reduction potential. The remediation mechanism encompassed a synergistic reduction of Cr(VI) to Cr(III) and simultaneous immobilization via Cr2FeO4 coprecipitation. The highest Cr(VI) removal capacity of 75 mg/g was attained during dynamic removal experiments in the sand column packed with S-nZVI. Further computational analysis, employing density functional theory calculations based on the experimental data, revealed the involvement of multiple molecular orbitals of Cr(VI) in the removal process. It also elucidated a step-by-step reduction pathway for Cr(VI) characterized by decreasing free energy. These findings provide evidence-based insights into Cr(VI) remediation using S-nZVI and can serve as valuable technical support for future environmental management of heavy metals.

DSP-KD: Dual-Stage Progressive Knowledge Distillation for Skin Disease Classification.

The increasing global demand for skin disease diagnostics emphasizes the urgent need for advancements in AI-assisted diagnostic technologies for dermatoscopic images. In current practical medical systems, the primary challenge is balancing lightweight models with accurate image analysis to address constraints like limited storage and computational costs. While knowledge distillation methods hold immense potential in healthcare applications, related research on multi-class skin disease tasks is scarce. To bridge this gap, our study introduces an enhanced multi-source knowledge fusion distillation framework, termed DSP-KD, which improves knowledge transfer in a dual-stage progressive distillation approach to maximize mutual information between teacher and student representations. The experimental results highlight the superior performance of our distilled ShuffleNetV2 on both the ISIC2019 dataset and our private skin disorders dataset. Compared to other state-of-the-art distillation methods using diverse knowledge sources, the DSP-KD demonstrates remarkable effectiveness with a smaller computational burden.

Effect of reactor operation modes on mitigating antibiotic resistance genes (ARGs) and methane production from hydrothermally-pretreated pig manure.

Numerous efforts have been made to enhance the performance of anaerobic digestion (AD) for accelerating renewable energy generation, however, it remains unclear whether the intensified measures could enhance the proliferation and transmissions of antibiotic resistance genes (ARGs) in the system. This study assessed the impact of an innovative pig manure AD process, which includes hydrothermal pretreatment (HTP) and a two-stage configuration with separated acidogenic and methanogenic phases, on biomethane (CH4) production and ARGs dynamics. Results showed that HTP significantly increase CH4 production from 0.65 to 0.75 L/L/d in conventional single-stage AD to 0.82 and 0.91 L/L/d in two-stage AD. This improvement correlated with a rise in the relative abundance of Methanosarcina, a key methanogenesis microorganism. In the two-stage AD, the methanogenic stage offered an ideal environment for methanogens growth, resulting in substantially faster and higher CH4 production by about 10% compared to single-stage AD. Overall, the combined use of HTP and the two-stage AD configuration enhanced CH4 production by 40% compared to traditional single-stage AD. The abundance and diversity of ARGs were significantly reduced in the acidogenic reactors after HTP. However, the ARGs levels increased by about two times in the following methanogenesis stage and reached similar or higher levels than in single stage AD. The erm(F), erm(G), ant(6)-Ia, tet(W), mef(A) and erm(B) were the six main ARGs with significant differences in relative abundances in various treatments. The two-stage AD mode could better remove sul2, but it also had a rebound which elevated the risk of ARGs to the environment and human health. Network analysis identified pH and TVFAs as critical factors driving microbial communities and ARG proliferation in the new AD process. With the results, this study offers valuable insights into the trade-offs between AD performance enhancement and ARG-related risks, pinpointing essential areas for future research and practical improvements.

Micropollutant rejection by nanofiltration membranes: A mini review dedicated to the critical factors and modelling prediction.

Nanofiltration (NF) membranes, extensively used in advanced wastewater treatment, have broad application prospects for the removal of emerging trace organic micropollutants (MPs). The treatment performance is affected by several factors, such as the properties of NF membranes, characteristics of target MPs, and operating conditions of the NF system concerning MP rejection. However, quantitative studies on different contributors in this context are limited. To fill the knowledge gap, this study aims to assess critical impact factors controlling MP rejection and develop a feasible model for MP removal prediction. The mini-review firstly summarized membrane pore size, membrane zeta potential, and the normalized molecular size (λ = rs/rp), showeing better individual relationships with MP rejection by NF membranes. The Lindeman-Merenda-Gold model was used to quantitatively assess the relative importance of all summarized impact factors. The results showed that membrane pore size and operating pressure were the high impact factors with the highest relative contribution rates to MP rejection of 32.11% and 25.57%, respectively. Moderate impact factors included membrane zeta potential, solution pH, and molecular radius with relative contribution rates of 10.15%, 8.17%, and 7.83%, respectively. The remaining low impact factors, including MP charge, molecular weight, logKow, pKa and crossflow rate, comprised all the remaining contribution rates of 16.19% through the model calculation. Furthermore, based on the results and data availabilities from references, the machine learning-based random forest regression model was trained with a relatively low root mean squared error and mean absolute error of 12.22% and 6.92%, respectively. The developed model was then successfully applied to predict MPs' rejections by NF membranes. These findings provide valuable insights that can be applied in the future to optimize NF membrane designs, operation, and prediction in terms of removing micropollutants.

Assessing the efficacy and mechanisms of glycol-contaminated water treatment through floating treatment wetlands.

The growing concerns surrounding water pollution and the degradation of ecosystems worldwide have led to an increased use of nature-based solutions (NbSs). This study assessed the feasibility of using floating treatment wetlands (FTWs) as an NbS to treat propylene glycol-contaminated water and quantitatively investigated different removal pathways. With an environmentally relevant concentration of propylene glycol (1,250 mg/L), FTWs containing Acorus calamus and mixed species demonstrated the highest average glycol mass removal efficacy (99%), followed by Carex acutiformis (98%), Juncus effusus (93%), and the control group without plants (10%) after 1 week. Additional mesocosm-scale experiments with varying FTW configurations, including surface coverage to reduce evaporation and photodegradation processes, and the addition of antibiotics to inhibit microbial activity, were conducted to quantify glycol removal pathways. Mass balance analysis results revealed that microbial biodegradation (33.3-39.7%) and plant uptake (37.9-45.2%) were the primary pathways for glycol removal. Only 15.5-19.5% of the glycol removal via evaporation and photodegradation was accounted in this study, which may be attributed to the mesocosm experimental setup (static water and no wind). Aligned with the broader discussion regarding biodiversity improvements and carbon storage capacity, this study demonstrated that FTWs are an environmentally friendly and effective NbS for addressing glycol-contaminated water.

China 6 EGR gasoline vehicles without a GPF may struggle to meet the potential SPN10 limit.

Particles larger than 10 nm from engine exhaust are gaining global concerns. In light of this, to investigate how EGR affects gasoline vehicle SPN10 (solid particles larger than 10 nm) emissions, seven gasoline vehicles (hybrid or conventional) were studied experimentally. The results revealed that EGR vehicles risk failing the current limit (6 * 1011 #/km) more than those without EGR if the cut-off size was tightened from 23 nm to 10 nm. More specifically, during the WLTC test, EGR increased the SPN10 emission factors by 2 âˆ¼ 3 times depending on vehicle powertrains (conventional or hybrid). Notably, SPN10 emissions increased significantly when EGR was actively engaged but showed a decrease when the EGR rate remained constant. EGR and the enriched fuel-air mixture are the critical reasons for the increased SPN10.

Enhanced biofuel production by co-pyrolysis of distiller's grains and waste plastics: A quantitative appraisal of kinetic behaviors and product characteristics.

Pyrolysis of biomass feedstocks can produce valuable biofuel, however, the final products may present excessive corrosion and poor stability due to the lack of hydrogen content. Co-pyrolysis with hydrogen-rich substances such as waste plastics may compensate for these shortcomings. In this study, the co-pyrolysis of a common biomass, i.e. distiller's grains (DG), and waste polypropylene plastic (PP) were investigated towards increasing the quantity and quality of the production of biofuel. Results from the thermogravimetric analyses showed that the reaction interval of individual pyrolysis of DG and PP was 124-471 °C and 260-461 °C, respectively. Conversely, an interaction effect between DG and PP was observed during co-pyrolysis, resulting in a slower rate of weight loss, a longer temperature range for the pyrolysis reaction, and an increase in the temperature difference between the evolution of products. Likewise, the Coats-Redfern model showed that the activation energies of DG, PP and an equal mixture of both were 42.90, 130.27 and 47.74 kJ mol-1, respectively. It thus follows that co-pyrolysis of DG and PP can effectively reduce the activation energy of the reaction system and promote the degree of pyrolysis. Synergistic effects essentially promoted the free radical reaction of the PP during co-pyrolysis, thereby reducing the activation energy of the process. Moreover, due to this synergistic effect in the co-pyrolysis of DG and PP, the ratio of elements was effectively optimized, especially the content of oxygen-containing species was reduced, and the hydrocarbon content of products was increased. These results will not only advance our understanding of the characteristics of co-pyrolysis of DG and PP, but will also support further research toward improving an efficient co-pyrolysis reactor system and the pyrolysis process itself.

Vonoprazan-based triple and dual therapy versus bismuth-based quadruple therapy for Helicobacter pylori infection in China: a three-arm, randomised clinical trial protocol.

BACKGROUND: Helicobacter pylori infection and associated diseases are a growing global public health issue. H. pylori infection is the major cause of gastric cancer, over 90% of duodenal ulcers, and over 70% of gastric ulcers. The infection rate of H. pylori is approximately 50%, and approximately 50% of new cases of gastric cancer worldwide occur in China. Bismuth (BI)-based quadruple therapy is recommended as the first-line treatment for H. pylori in China. Vonoprazan (VPZ), a new potassium-competitive acid blocker that can inhibit gastric acid secretion more effectively than proton pump inhibitors (PPIs), has been combined with antibiotics to effectively eradicate H. pylori. In this study, we compared the efficacy and safety of two VPZ-based therapies with that of BI-based therapy for H. pylori treatment. METHODS: A three-armed randomised controlled trial (RCT) is being conducted in Shenzhen, with 327 participants recruited from the Gastroenterology Clinic of the University of Hong Kong-Shenzhen Hospital. Patients were diagnosed with H. pylori infection based on a positive 13C-urea breath test (UBT). Patients are kept naïve to their treatment and are randomly assigned in a 1:1:1 ratio to either VPZ-based triple, VPZ-based dual, or BI-based quadruple therapy for 14 days. All groups are subjected to follow-up evaluations of safety, adverse drug reactions, and clinical variables in the first, second, and fourth weeks after treatment. Successful eradication is confirmed by a negative 13C-UBT six weeks after treatment. If initial treatment fails, (1) those patients are turned to another regimen, or (2) a drug resistance test is conducted, after which an individualised treatment regimen shall be prescribed according to antimicrobial susceptibility testing. The resulting data will be evaluated using intention-treat and a per-protocol analysis. DISCUSSION: This study is the a RCT aims to evaluate the efficacy and safety of 14-day VPZ-based triple and dual therapies in comparison with BI-based quadruple therapy. The outcomes of this study may allow treatment recommendations and update drug instructions in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=141314.

Single-cell transcriptomics reveals cellular heterogeneity and macrophage-to-mesenchymal transition in bicuspid calcific aortic valve disease.

BACKGROUND: Bicuspid aortic valve (BAV) is the most prevalent congenital valvular heart defect, and around 50% of severe isolated calcific aortic valve disease (CAVD) cases are associated with BAV. Although previous studies have demonstrated the cellular heterogeneity of aortic valves, the cellular composition of specific BAV at the single-cell level remains unclear. METHODS: Four BAV specimens from aortic valve stenosis patients were collected to conduct single-cell RNA sequencing (scRNA-seq). In vitro experiments were performed to further validate some phenotypes. RESULTS: The heterogeneity of stromal cells and immune cells were revealed based on comprehensive analysis. We identified twelve subclusters of VICs, four subclusters of ECs, six subclusters of lymphocytes, six subclusters of monocytic cells and one cluster of mast cells. Based on the detailed cell atlas, we constructed a cellular interaction network. Several novel cell types were identified, and we provided evidence for established mechanisms on valvular calcification. Furthermore, when exploring the monocytic lineage, a special population, macrophage derived stromal cells (MDSC), was revealed to be originated from MRC1+ (CD206) macrophages (Macrophage-to-Mesenchymal transition, MMT). FOXC1 and PI3K-AKT pathway were identified as potential regulators of MMT through scRNA analysis and in vitro experiments. CONCLUSIONS: With an unbiased scRNA-seq approach, we identified a full spectrum of cell populations and a cellular interaction network in stenotic BAVs, which may provide insights for further research on CAVD. Notably, the exploration on mechanism of MMT might provide potential therapeutic targets for bicuspid CAVD.

Nanobubble aeration enhanced wastewater treatment and bioenergy generation in constructed wetlands coupled with microbial fuel cells.

Artificial aeration is a widely used approach in wastewater treatment to enhance the removal of pollutants, however, traditional aeration techniques have been challenging due to the low oxygen transfer rate (OTR). Nanobubble aeration has emerged as a promising technology that utilise nano-scale bubbles to achieve higher OTRs owing to their large surface area and unique properties such as longevity and reactive oxygen species generation. This study, for the first time, investigated the feasibility of coupling nanobubble technology with constructed wetlands (CWs) for treating livestock wastewater. The results demonstrated that nanobubble-aerated CWs achieved significantly higher removal efficiencies of total organic carbon (TOC) and ammonia (NH4+-N), at 49 % and 65 %, respectively, compared to traditional aeration treatment (36 % and 48 %) and the control group (27 % and 22 %). The enhanced performance of the nanobubble-aerated CWs can be attributed to the nearly three times higher amount of nanobubbles (Ø < 1 µm) generated from the nanobubble pump (3.68 × 108 particles/mL) compared to the normal aeration pump. Moreover, the microbial fuel cells (MFCs) embedded in the nanobubble-aerated CWs harvested 5.5 times higher electricity energy (29 mW/m2) compared to the other groups. The results suggested that nanobubble technology has the potential to trigger the innovation of CWs by enhancing their capacity for water treatment and energy recovery. Further research needs are proposed to optimise the generation of nanobubbles, allowing them to be effectively coupled with different technologies for engineering implementation.

Sono-Driven STING Activation using Semiconducting Polymeric Nanoagonists for Precision Sono-Immunotherapy of Head and Neck Squamous Cell Carcinoma.

Immunotherapy has offered new opportunities to treat head and neck squamous cell carcinoma (HNSCC); however, its clinical applications are hindered by modest therapeutic outcomes and the "always-on" pharmacological activity of immunomodulatory agents. Strategies for precise spatiotemporal activation of antitumor immunity can tackle these issues but remain challenging. Herein, a semiconducting polymeric nanoagonist (SPNM) with in situ sono-activatable immunotherapeutic effects for precision sono-immunotherapy of HNSCC is reported. SPNM is self-assembled from a sonodynamic semiconducting polymer core conjugated with a stimulator of interferon genes (STING) agonist (MSA-2) via a singlet oxygen cleavable linker. Under sono-irradiation, SPNM produces singlet oxygen not only to eradicate tumor cells to trigger immunogenic cell death but also to unleash caged STING agonists via the cleavage of diphenoxyethene bonds for in situ activation of the STING pathway in the tumor region. Such sono-driven STING activation mediated by SPNM promotes effector T cell infiltration and potentiates systemic antitumor immunity, eventually leading to tumor growth inhibition and long-term immunological memory. This study thus presents a promising strategy for the precise spatiotemporal activation of cancer immunotherapy.

Whole genome sequencing reveals novel genetic mutations of Helicobacter pylori associating with resistance to clarithromycin and levofloxacin.

BACKGROUND: Detection of mutations in one or a couple of genes may not provide enough data or cover all the genomic DNA variance related to antibiotic resistance of Helicobacter pylori to clarithromycin (CLA) and levofloxacin (LVX). We aimed to perform whole genome sequencing to explore novel antibiotic resistance-related genes to increase predictive accuracy for future targeted sequencing tests. METHODS: Gastric mucosal biopsies were taken during upper endoscopy in 27 H. pylori-infected patients. According to culture-based antibacterial susceptibility test, H. pylori strains were divided into three groups, with nine strains in each group: CLA single-drug resistance (group C), LVX single-drug resistance (group L), and strains sensitive to all antibacterial drugs (group S). Based on whole genome sequencing with group S being the control, group C and group L group-specific single nucleotide variants and amino acid mutations were screened, and potential candidate genes related to CLA and LVX resistance were identified. RESULTS: The median age of study subjects was 35 years (IQR: 31-40), and 17 (63.0%) were male. All nine CLA-resistant strains had A2143G mutations in 23S rRNA, while none of nine sensitive strains had the mutation. Six of nine strains in group L and six of nine strains in group S had 87th or 91st mutation in gyrA. After comparing sequencing data of strains among the three groups, we identified five mutated positions belonging to four genes related to CLA resistance, and 31 mutated positions belonging to 20 genes related to LVX resistance. Novel genetic mutations were detected for CLA resistance (including fliJ and clpX) and LVX resistance (including fliJ, cheA, hemE, Val360Ile, and HP0568). Missense mutations in fliJ and cheA gene were mainly involved in chemotaxis and flagellar motility to facilitate bacterial escape of antibiotics, while the functions of other novel gene mutations underpinning antibiotic resistance remain to be investigated. CONCLUSION: Whole genome sequencing detected potential novel genetic mutations conferring resistance of H. pylori to CLA and LVX including fliJ and cheA. Further studies to correlate these findings with treatment outcome should be performed.

A modelling approach to explore the optimum bubble size for micro-nanobubble aeration.

Bubble aeration has been widely applied in water/wastewater treatment, however its low gas utilization rate results in high energy consumption. Application of micro-nanobubbles (MNB) has emerged as a process with the potential to significantly increase gas utilisation due to their high relative surface area and high gas-liquid mass transfer efficiency. In this study, we demonstrate through calibrated models that MNB of an optimum bubble size can shrink and burst at or below the water surface enabling (1) all encapsulated gas to thoroughly dissolve in water, and (2) the bursting of nanobubbles to potentially generate free radicals. Through the understanding of MNB dimensional characteristics and bubble behaviour in water, a dynamic model that integrated force balance (i.e. buoyancy force, gravity, drag force, Basset force and virtual mass force), and mass transfer was developed to describe the rising velocity and radius variation of MNB along its upward trajectory. Unlike for conventional millimetre-sized bubbles, intensive gas dissolution of MNBs led to radius reduction for small bubbles, while a large initial radius triggers bubble swelling. The initial water depth was also crucial, where greater depth could drive the potential for bubble shrinkage so that they were more liable to contract. For example, the optimum bubble size of air (42-194 µm) and oxygen (127-470 µm) MNB that could achieve complete gas transfer (100% gas utilisation) for a range of specific water depths (0.5-10 m) were calculated. The modelling results for microbubbles (10-530 µm) were well validated by the experimental data (R2>0.85). However, the validation of the modelling results for nanobubble (<1 µm) aeration requires further study due to a lack of available empirical data. In this study, the proposed model and analysis provided new insights into understanding bubble dynamics in water and offered fundamental guidance for practitioners looking to upgrade bubble aeration system.

LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/ß-catenin activation via interacting with hnRNPC.

BACKGROUND: Hepatocellular carcinoma (HCC) is the world's third leading cause of cancer-related death; due to the fast growth and high prevalence of tumor recurrence, the prognosis of HCC patients remains dismal. Long non-coding RNA CEBPA-DT, a divergent transcript of the CCAAT Enhancer Binding Protein Alpha (CEBPA) gene, has been shown to participate in multiple tumor progression. However, no research has established its cancer-promoting mechanism in HCC yet. METHODS: CEBPA-DT was identified in human HCC tissues through RNA sequencing. The expression level of CEBPA-DT was assessed by quantitative real-time PCR. The biological effects of CEBPA-DT were evaluated in vitro and in vivo through gain or loss of function experiments. RNA fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were applied to investigate the downstream target of CEBPA-DT. Immunofluorescence, subcellular protein fractionation, western blot, and co-immunoprecipitation were performed to analyze the subcellular location of ß-catenin and its interaction with Discoidin domain-containing receptor 2 (DDR2). RESULTS: CEBPA-DT was upregulated in human HCC tissues with postoperative distant metastasis and intimately related to the worse prognosis of HCC patients. Silencing of CEBPA-DT inhibited the growth, migration and invasion of hepatoma cells in vitro and in vivo, while enhancement of CEBPA-DT played a contrasting role. Mechanistic investigations demonstrated that CEBPA-DT could bind to heterogeneous nuclear ribonucleoprotein C (hnRNPC), which facilitated cytoplasmic translocation of hnRNPC, enhanced the interaction between hnRNPC and DDR2 mRNA, subsequently promoted the expression of DDR2. Meanwhile, CEBPA-DT induced epithelial-mesenchymal transition (EMT) process through upregulation of Snail1 via facilitating nuclear translocation of ß-catenin. Using DDR2 inhibitor, we revealed that the CEBPA-DT induced the interaction between DDR2 and ß-catenin, thus promoting the nuclear translocation of ß-catenin to activate transcription of Snail1, contributing to EMT and HCC metastasis. CONCLUSIONS: Our results suggested that CEBPA-DT promoted HCC metastasis through DDR2/ß-catenin mediated activation of Snail1 via interaction with hnRNPC, indicating that the CEBPA-DT-hnRNPC-DDR2/ß-catenin axis may be used as a potential therapeutic target for HCC treatment.