Resistance of Nile tilapia fed with Padina boergesenii extract to Pseudomonas putida infection.

The aim of this research was to estimate the immunopotentiation effect of brown algae Padina boergesenii water extract on Nile tilapia, Oreochromis niloticus through resistance to Pseudomonas putida infection. Gas Chromatography Mass Spectrometry was utilized to characterize the seaweed phytoconstituents. One hundred and twenty-six fish were divided in triplicates into two equal groups corresponding to two diet variants that used to feed Nile tilapia for 20 successive days: a basal (control), and P. boergesenii water extract supplemented group. Fish samples were collected at 10-days intervals throughout the experiment. Serum biochemical constituents, total antioxidant capacity (TAC), and some immune related genes expression of the spleen and intestinal tissues of experimental fish were studied, as well as histological examination of fish immune tissues. Moreover, following 20 days of feeding, the susceptibility of Nile tilapia to P. putida infection was evaluated to assess the protective effect of the used extract. The findings indicated that the studied parameters were significantly increased, and the best immune response profiles were observed in fish fed P. boergesenii water extract for 20 successive days. A bacterial challenge experiment using P. putida resulted in higher survival within the supplemented fish group than the control. Thus, the lowered post-challenge mortality of the fish may be related to the protection provided by the stimulation of the innate immune system, reduced oxidative stress by higher activity of TAC, and elevated levels of expression of iterleukin-1beta (IL-1ß), beta-defensin (ß-defensin), and natural killer-lysin (NKl). Moreover, the constituents of the extract used showed potential protective activity for histological features of the supplemented fish group when compared to the control. Collectively, this study presents a great insight on the protective role of P. boergesenii water extract as an additive in Nile tilapia feed which suggests its potential for improving the immune response against P. putida infection.

Pontederia crassipes utilization for dual phytoremediation and adsorption in greywater treatment: a techno-economic and sustainable approach.

While phytoremediation has been widely employed for greywater treatment, this system suffers from the transfer of considerable amounts of surfactants to the aquatic environment through partially treated effluent and/or exhausted plant disposal. Hence, this study focuses on greywater phytoremediation followed by recycling the spent plant for preparing an adsorbent material used as post-treatment. P. crassipes was used to operate a phytoremediation unit under 23 °C, 60% relative humidity, plant density (5-30 g/L), dilution (0-50%), pH (4-10), and retention time (3-15 days). The optimum condition was 12.7 g/L density, 34.0% dilution, pH 8.4, and 13 days, giving chemical oxygen demand (COD), surfactant, and NH4-N removal efficiencies of 94.62%, 90.45%, and 88.09%, respectively. The exhausted plant was then thermally treated at 550 °C and 40 min to obtain biochar used as adsorbent to treat the phytoremediation effluent. The optimum adsorption process was biochar dosage of 1.51 g/L, pH of 2.1, and 137 min, providing a surfactant removal efficiency of 92.56%. The final discharge of this phytoremediation/adsorption combined process contained 8.30 mg/L COD, 0.23 mg/L surfactant, and 0.94 mg/L NH4+-N. Interestingly, this approach could be economically feasible with a payback period of 6.5 years, 14 USD net present value, and 8.6% internal rate of return.

The research succeeded in treating greywater by phytoremediation followed by recycling the exhausted P. crassipes plant to prepare an adsorbent material used in the post-treatment phase, giving an economically feasible scenario with 6.5-year payback period.

MicroRNA-141-regulated KLK10 and TNFSF-15 gene expression in hepatoblastoma cells as a novel mechanism in liver carcinogenesis.

Liver cancer is one of the most pivotal global health problems, leading hepatocellular carcinoma (HCC) with a significant increase in cases worldwide. The role of non-coding-RNA in cancer proliferation and carcinogenesis has attracted much attention in the last decade; however, microRNAs (miRNAs), as non-coding RNA, are considered master mediators in various cancer progressions. Yet the role of miR-141 as a modulator for specific cellular processes in liver cancer cell proliferation is still unclear. This study identified the role of miR-141 and its potential functions in liver carcinogenesis. The level of miR-141 in HepG2 and HuH7 cells was assessed using quantitative real-time PCR (qRT-PCR) and compared with its expression in normal hepatocytes. A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HepG2 cells. The protein profile of the kallikrein-related peptidase 10 (KLK10) and tumor necrosis factor TNFSF-15 was investigated in HepG2 cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced inflammatory cytokines from transfected HepG2 cells. Our findings showed that the expression of miR-141 significantly increased in HepG2 and HuH7 cells compared to the normal hepatocytes. Transfection of HepG2 cells with an inhibitor, antagonist miR-141, showed a significant reduction of HepG2 cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HepG2 cells overexpressed miR-141 provided a hundred downregulated genes, including KLK10 and TNFSF-15. Furthermore, the expression profile of KLK10 and TNFSF-15 markedly depleted in HepG2 cells transfected with miR-141 overexpression accompanied by a decreasing level of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α), indicating the role of miR-141 in HepG2 cell proliferation and programmed cell death. Interestingly, the experimental rats with liver cancer induced by Diethylnitrosamine injection further confirmed the upregulation of miR-141 level, IL-10, and TNF-α and the disturbance in KLK10 and TNFSF-15 gene expression compared with their expression in normal rats. The in-silico online tools, IntaRNA and miRWalk were used to confirm the direct interaction and potential binding sites between miR-141 and identified genes. Thus, the seeding regions of potential targeted sequences was cloned upstream of luciferase reporter gene in pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HepG2 cells pre-transfected with miR-141 overexpression vector, while increasing in cells pre-transfected with miR-141 specific inhibitor. In summary, these data suggest the crucial role of miR-141 in liver cancer development via targeting KLK10 and TNFSF-15 and provide miR-141 as an attractive candidate in liver cancer treatment and protection.

Engineering nanomedicines for immunogenic eradication of cancer cells: Recent trends and synergistic approaches.

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment (TME) leading to failure of immune response. Numerous therapeutic strategies including chemotherapy, radiotherapy, photodynamic, photothermal, magnetic, chemodynamic, sonodynamic and oncolytic therapy, have been developed to induce immunogenic cell death (ICD) of cancer cells and thereby elicit immunogenicity and boost the antitumor immune response. However, many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic response. Here, we outline the current state of using nanomedicines for boosting ICD of cancer cells. Moreover, synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints, phagocytosis, macrophage polarization, tumor hypoxia, autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were analyzed. We further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune responses. Endoplasmic reticulum localized ICD, focused ultrasound hyperthermia, cell membrane camouflaged nanomedicines, amplified reactive oxygen species (ROS) generation, metallo-immunotherapy, ion modulators and engineered bacteria are among the most innovative approaches. Various challenges, merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

Synergism of floated paperboard sludge cake /sewage sludge for maximizing biomethane yield and biochar recovery from digestate: A step towards circular economy.

Anaerobic digestion of floated paperboard sludge (PS) cake suffers from volatile fatty acids (VFAs) accumulation, nutrient unbalanced condition, and generation of digestate with a risk of secondary pollution. To overcome these drawbacks, sewage sludge (SS) was added to PS cake for biogas recovery improvement under a co-digestion process followed by the thermal treatment of solid fraction of digestate for biochar production. Batch experimental assays were conducted at different SS:PS mixing ratios of 70:30, 50:50, 30:70, and 20:80 (w/w), and their anaerobic co-digestion performances were compared to the mono-digestion systems at 35 ± 0.2 °C for 45 days. The highest methane yield (MY) of 241.68 ± 14.81 mL/g CODremoved was obtained at the optimum SS:PS ratio of 50:50 (w/w). This experimental condition was accompanied by protein, carbohydrate, and VFA conversion efficiencies of 47.3 ± 3.2%, 46.8 ± 3.2%, and 56.3 ± 3.8%, respectively. The synergistic effect of SS and PS cake encouraged the dominance of Bacteroidota (23.19%), Proteobacteria (49.65%), Patescibacteria (8.12%), and Acidovorax (12.60%) responsible for hydrolyzing the complex organic compounds and converting the VFAs into biomethane. Further, the solid fraction of digestate was subjected to thermal treatment at a temperature of 500 °C for 2.0 h, under an oxygen-limited condition. The obtained biochar had a yield of 0.48 g/g dry digestate, and its oxygen-to-carbon (O/C), carbon-to-nitrogen (C/N), and carbon-to-phosphorous (C/P) ratios were 0.55, 10.23, and 16.42, respectively. A combined anaerobic co-digestion/pyrolysis system (capacity 50 m3/d) was designed based on the COD mass balance experimental data and biogenic CO2 market price of 22 USD/ton. This project could earn profits from biogas (12,565 USD/yr), biochar (6641 USD/yr), carbon credit (8014 USD/yr), and COD shadow price (6932 USD/yr). The proposed project could maintain a payback period of 6.60 yr. However, further studies are required to determine the associated life cycle cost model that is useful to validate the batch experiment assumptions.

Biochar-enhanced anaerobic mixed culture for biodegradation of 1,2-dichloroethane: Microbial community, mechanisms, and techno-economics.

While anaerobic digestion (AD) has been employed for the degradation of chlorinated aliphatic hydrocarbons, the associated digester performance might suffer from volatile fatty acids accumulation, insufficient substrate-microbes interaction, and lower biogas yields. To overcome these limitations, this study is the first to augment the hydrocarbon-degrading microbial capacities by adding agricultural waste-based biochar to the digestion medium. 1,2-dichloroethane (1,2-DCA) was selected as the target pollutant because it is discharged in large quantities from oil refining, petrochemical, and chemical industries, causing serious environmental and human health concerns. A multi-chamber anaerobic reactor (MAR) was operated at a 1,2-DCA loading rate of 1.13 g/L/d, glucose dosage (as an electron donor) range of 200-700 mg/L, and hydraulic retention time of 11.2 h, giving dechlorination = 32.2 ± 6.9% and biogas yield = 210 ± 30 mL/g CODremoved. These values increased after biochar supplementation (100 mg/g volatile solids, VS, as an inoculum carrier) up to 60.2 ± 11.5% and 290 ± 40 mL/g CODremoved, respectively, owing to the enhancement of dehydrogenase enzyme activities. Burkholderiales (15.3%), Clostridiales (2.3%), Bacteroidales (3.5%), Xanthomonadales (3.3%), and Rhodobacterales (6.1%) involved in 1,2-DCA degradation were dominant in the reactor supplemented with biochar. It's suggested that biochar played a major role in facilitating the direct interspecies electron transfer (DIET) between syntrophic bacteria and methanogens, where chloride, ethylene glycol, and acetate derived from 1,2-DCA dechlorination could be further used to promote methanogenesis and methane production. The synergetic effect of adsorption and dechlorination towards 1,2-DCA removal was validated at various biochar dosages (50-120 mg/g) and 1,2-DCA concentrations (50-1000 mg/L). The techno-economic results showed that the cost of treating 1,2-DCA-laden discharge (100 m3/d) by the MAR module could be 0.83 USD/m3 with a payback period of 6.24 years (NPV = 2840 USD and IRR = 10%), retrieving profits from pollution reduction (9542 USD/yr), biogas selling (10418 USD/yr), and carbon credit (10294 USD/yr).

Advancing sustainable water treatment strategies: harnessing magnetite-based photocatalysts and techno-economic analysis for enhanced wastewater management in the context of SDGs.

Herein, we explore the holistic integration of magnetite-based photocatalysts and techno-economic analysis (TEA) as a sustainable approach in wastewater treatment aligned with the Sustainable Development Goals (SDGs). While considerable attention has been devoted to photocatalytic dye degradation, the nexus between these processes and techno-economic considerations remains relatively unexplored. The review comprehensively examines the fundamental characteristics of magnetite-based photocatalysts, encompassing synthesis methods, composition, and unique properties. It investigates their efficacy in photocatalytic degradation, addressing homogeneous and heterogeneous aspects while discussing strategies to optimize photodegradation efficiency, including curbing electron-hole recombination and mitigating scavenging effects and interference by ions and humic acid. Moreover, the management aspects of magnetite-based photocatalysts are examined, focusing on their reusability and regeneration post-dye removal, along with the potential for reusing treated wastewater in relevant industrial applications. From a techno-economic perspective, the study evaluates the financial feasibility of deploying magnetite-based photocatalysts in wastewater treatment, correlating reduced pollution and the marketing of treated water with social, economic, and environmental objectives. By advocating the integration of magnetite-based photocatalysts and TEA, this paper contributes insights into scalable and profitable sustainable wastewater treatment practices. It underscores the alignment of these practices with SDGs, emphasizing a comprehensive and holistic approach to managing wastewater in ways that meet environmental, economic, and societal objectives.

Artificial intelligence-enabled optimization of Fe/Zn@biochar photocatalyst for 2,6-dichlorophenol removal from petrochemical wastewater: A techno-economic perspective.

While numerous studies have addressed the photocatalytic degradation of 2,6-dichlorophenol (2,6-DCP) in wastewater, an existing research gap pertains to operational factors' optimization by non-linear prediction models to ensure a cost-effective and sustainable process. Herein, we focus on optimizing the photocatalytic degradation of 2,6-DCP using artificial intelligence modeling, aiming at minimizing initial capital outlay and ongoing operational expenses. Hence, Fe/Zn@biochar, a novel material, was synthesized, characterized, and applied to harness the dual capabilities of 2,6-DCP adsorption and degradation. Fe/Zn@biochar exhibited an adsorption energy of -21.858 kJ/mol, effectively capturing the 2,6-DCP molecules. This catalyst accumulated photo-excited electrons, which, upon interaction with adsorbed oxygen and/or dissolved oxygen generated •O2-. The •OH radicals could also be produced from h+ in the Fe/Zn@biochar valence band, cleaving the C-Cl bonds to Cl- ions, dechlorinated byproducts, and phenols. An artificial neural network (ANN) model, with a 4-10-1 topology, "trainlm" training function, and feed-forward back-propagation algorithm, was developed to predict the 2,6-DCP removal efficiency. The ANN prediction accuracy was expressed as R2 = 0.967 and mean squared error = 5.56e-22. The ANN-based optimized condition depicted that over 90% of 2,6-DCP could be eliminated under C0 = 130 mg/L, pH = 2.74, and catalyst dosage = 168 mg/L within ∼4 h. This optimum condition corresponded to a total cost of $7.70/m3, which was cheaper than the price estimated from the unoptimized photocatalytic system by 16%. Hence, the proposed ANN could be employed to enhance the 2,6-DCP photocatalytic degradation process with reduced operational expenses, providing practical and cost-effective solutions for petrochemical wastewater treatment.

Utilizing Undissolved Portion (UNP) of Cement Kiln Dust as a Versatile Multicomponent Catalyst for Bioethylene Production from Bioethanol: An Innovative Approach to Address the Energy Crisis.

This study focuses on upcycling cement kiln dust (CKD) as an industrial waste by utilizing the undissolved portion (UNP) as a multicomponent catalyst for bioethylene production from bioethanol, offering an environmentally sustainable solution. To maximize UNP utilization, CKD was dissolved in nitric acid, followed by calcination at 500 °C for 3 h in an oxygen atmosphere. Various characterization techniques confirmed that UNP comprises five different compounds with nanocrystalline particles exhibiting an average crystal size of 47.53 nm. The UNP catalyst exhibited a promising bioethylene yield (77.1%) and selectivity (92%) at 400 °C, showcasing its effectiveness in converting bioethanol to bioethylene with outstanding properties. This exceptional performance can be attributed to its distinctive structural characteristics, including a high surface area and multiple-strength acidic sites that facilitate the reaction mechanism. Moreover, the UNP catalyst displayed remarkable stability and durability, positioning it as a strong candidate for industrial applications in bioethylene production. This research underscores the importance of waste reduction in the cement industry and offers a sustainable path toward a greener future.

Dual phytoremediation and biochar production by Eichhornia crassipes in hydroponic system receiving different 1,4-dioxane dosages.

This study focuses on applying phytoremediation as a low-effective and simple process to treat wastewater laden with 1,4 dioxane (DIOX). A floating macrophyte (Eichhornia crassipes) was cultivated under hydroponic conditions (relative humidity 50-67%, photoperiod cycle 18:6 h light/dark, and 28-33 °C) and subjected to different DIOX loads between 0.0 (control) and 11.5 mg/g fresh mass (FM). The aquatic plant achieved DIOX and chemical oxygen demand (COD) removal efficiencies of 76-96% and 67-94%, respectively, within 15 days. E. crassipes could tolerate elevated DIOX-associated stresses until a dose of 8.2 mg DIOX/g, which highly influenced the oxidative defense system. Malondialdehyde (MDA) content, hydrogen peroxide (H2O2), and total phenolic compounds (TPC) increased by 7.3, 8.4, and 4.5-times, respectively, in response to operating the phytoremediation unit at a DIOX load of 11.5 mg/g. The associated succulent value, proteins, chlorophyll-a, chlorophyll-b, and pigments dropped by 39.6%, 45.8%, 51.5%, 80.8%, and 55.5%, respectively. The suggested removal mechanism of DIOX by E. crassipes could be uptake followed by phytovolatilization, whereas direct photodegradation from sunlight contributed to about 19.36% of the total DIOX removal efficiencies. Recycling the exhausted E. crassipes for biochar production was a cost-efficient strategy, making the payback period of the phytoremediation project equals to 6.96 yr.

Eichhornia crassipes could be used in phytoremediation of 1,4 dioxane (DIOX)-laden water at DIOX load< 8.2 mg/g FM. E. crassipes removed 77­97% DIOX via uptake and phytovolatilization. Recycling exhausted-plant to produce biochar was cost-efficient with 7 yr-payback period.

Enhanced synergistic system for the persulfate activation under visible light using novel N-ZnO photocatalyst supported on Lantana camara-based biochar.

Herein, a novel nitrogen-doped ZnO photocatalyst supported on biochar (N-ZnO@LBC) was synthesized using the Lantana camera as a green source of biochar. The synthesized photocatalyst was applied as an activator of persulfate (PS) for the photodegradation of methylene blue (MB) under visible light irradiation. The properties of the synthesized photocatalyst were explored before and after photocatalysis using different characterization analyses. The results revealed that the nitrogen doping of ZnO@LBC could reduce the band gap energy from 2.83 eV to 2.78 eV resulting in higher activity under visible light. The synergetic effect of the N-ZnO@LBC/PS/visible process was investigated under various reaction conditions. Surprisingly, about 95.7% of MB photodegradation could be achieved using N-ZnO@LBC/PS/visible process under optimal conditions. Moreover, a prediction model with an excellent correlation between the actual and predicted data (R2 = 0.9844) was established to forecast MB removal. Interestingly, the scavenging tests exhibited that various reactive species could induce MB degradation in an order of O2-• > h+ > SO4-• >•OH with the highest contribution of O2-•. Additionally, the presence of functional hydroxyl groups in the N-ZnO@LBC structure could lead to the generation of additional radicals as confirmed by FT-IR analysis after photocatalysis. The reusability test showed that the photocatalyst could be reused for up to five cycles without a significant loss in the photocatalytic activity indicating its high stability. The cost of wastewater treatment by N-ZnO@LBC/PS/Visible process was estimated to be US$ 9.79/m3 based on an economic analysis. It worth mentioning that the proposed process was investigated for the degradation of other dyes including Congo red (CR) and methyl orange (MO) and the efficiencies were 65.41% and 59.23% for CR and MO, respectively. Overall, the proposed process could be a promising and cost-effective approach for the degradation of various dyes in real applications.

Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens.

The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin-phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag. Monophosphoryl-lipid (MPLA) and QS-21 were incorporated as immunostimulatory adjuvants to enhance vaccine responses. Following optimization of nanodisc assembly, spike proteins were effectively displayed on the surface of the nanodiscs and maintained their conformational capacity for binding with human angiotensin-converting enzyme 2 (hACE2) as verified using electron microscopy and slot blot assay, respectively. Six different formulations were prepared where they contained mono antigens; four from the year 2020 (WT, Beta, Lambda, and Delta) and two from the year 2021 (Omicron BA.1 and BA.2). Additionally, we prepared a mosaic nanodisc displaying the four spike proteins from year 2020. Intramuscular vaccination of CD-1 female mice with the mosaic nanodisc induced antibody responses that not only neutralized matched pseudo-typed viruses, but also neutralized mismatched pseudo-typed viruses corresponding to later variants from year 2021 (Omicron BA.1 and BA.2). Interestingly, sera from mosaic-immunized mice did not effectively inhibit Omicron spike binding to human ACE-2, suggesting that some of the elicited antibodies were directed towards conserved neutralizing epitopes outside the receptor binding domain. Our results show that mosaic nanodisc vaccine displaying spike proteins from 2020 can elicit broadly neutralizing antibodies that can neutralize mismatched viruses from a following year, thus decreasing immune evasion of new emerging variants and enhancing healthcare preparedness.

Retention and recycling of granules in continuous flow-through system to accomplish denitrification and perchlorate reduction.

This study employed a completely anoxic reactor and a gravity-settling design for continuously capturing and separating granules from flocculated biomass, and recycling granules back to the main reactor. The average chemical oxygen demand (COD) removal in the reactor was 98%. Average nitrate (NO3--N) and perchlorate (ClO4-) removal efficiencies of 99% and 74 ± 19% were observed, respectively. Preferential utilization of NO3- over ClO4- led to COD limiting conditions, which resulted in ClO4- in the effluent. The average granule diameter in continuous flow-through bubble-column (CFB) anoxic granular sludge (AxGS) bioreactor was 6325 ± 2434 µm, and the average SVI30/SVI1 was >90 % throughout its operation. 16s rDNA amplicon sequencing revealed Proteobacteria (68.53%-88.57%) and Dechloromonas (10.46%-54.77%) to be the most abundant phylum and the genus present in reactor sludge representing the denitrifying and ClO4- reducing microbial community. This work represents a pioneering development of CFB-AxGS bioreactor.

Serial image interpretation tasks improve accuracy and increase confidence in Level 1 echocardiography reporting: a pilot study.

BACKGROUND: Focused echocardiography is increasingly used in acute and emergency care, with point-of-care ultrasound integrated into several specialist training curricula (e.g. Emergency Medicine, Cardiology, Critical Care). Multiple accreditation pathways support development of this skill but there is scant empirical evidence to inform selection of teaching methods, accreditation requirements or quality assurance of education in focussed echocardiography. It has also been noted that access to in-person teaching can be a barrier to completing accreditation programmes, and that this may affect learners disproportionately depending on the location or nature of their institution. The purpose of the study was to determine whether serial image interpretation tasks as a distinct learning tool improved novice echocardiographers' ability to accurately identify potentially life-threatening pathology from focused scans. We also aimed to describe the relationship between accuracy of reporting and participants' confidence in those reports, and to assess users' satisfaction with a learning pathway that could potentially be delivered remotely. METHODS: 27 participants from a variety of healthcare roles completed a program of remote lectures and 2 in-person study days. During the program they undertook 4 'packets' of 10 focused echocardiography reporting tasks (total = 40) based on images from a standardised dataset. Participants were randomized to view the scans in varying orders. Reporting accuracy was compared with consensus reports from a panel of expert echocardiographers, and participants self-reported confidence in their image interpretation and their satisfaction with the learning experience. RESULTS: There was a stepwise improvement in reporting accuracy with each set of images reported, from an average reporting score of 66% for the 1st packet to 78% for the 4th packet. Participants felt more confident in identifying common life-threatening pathologies as they reported more echocardiograms. The correlation between report accuracy and confidence in the report was weak and did not increase during the study (rs = 0.394 for the 1st packet, rs = 0.321 for the 4th packet). Attrition during the study related primarily to logistical issues. There were high levels of satisfaction amongst participants, with most reporting that they would use and / or recommend a similar teaching package to colleagues. CONCLUSIONS: Healthcare professionals undertaking remote training with recorded lectures, followed by multiple reporting tasks were capable of interpreting focused echocardiograms. Reporting accuracy and confidence in identifying life-threatening pathology increased with the number of scans interpreted. The correlation between accuracy and confidence for any given report was weak (and this relationship should be explored further given the potential safety considerations). All components of this package could be delivered via distance learning to enhance the flexibility of echocardiography education.

High-Throughput/High Content Imaging Screen Identifies Novel Small Molecule Inhibitors and Immunoproteasomes as Therapeutic Targets for Chordoma.

Chordomas account for approximately 1-4% of all malignant bone tumors and 20% of primary tumors of the spinal column. It is a rare disease, with an incidence estimated to be approximately 1 per 1,000,000 people. The underlying causative mechanism of chordoma is unknown, which makes it challenging to treat. Chordomas have been linked to the T-box transcription factor T (TBXT) gene located on chromosome 6. The TBXT gene encodes a protein transcription factor TBXT, or brachyury homolog. Currently, there is no approved targeted therapy for chordoma. Here, we performed a small molecule screening to identify small chemical molecules and therapeutic targets for treating chordoma. We screened 3730 unique compounds and selected 50 potential hits. The top three hits were Ribociclib, Ingenol-3-angelate, and Duvelisib. Among the top 10 hits, we found a novel class of small molecules, including proteasomal inhibitors, as promising molecules that reduce the proliferation of human chordoma cells. Furthermore, we discovered that proteasomal subunits PSMB5 and PSMB8 are increased in human chordoma cell lines U-CH1 and U-CH2, confirming that the proteasome may serve as a molecular target whose specific inhibition may lead to better therapeutic strategies for chordoma.

Polyaromatic hydrocarbons (PAHs) in the water environment: A review on toxicity, microbial biodegradation, systematic biological advancements, and environmental fate.

Polycyclic aromatic hydrocarbons (PAHs) are considered a major class of organic contaminants or pollutants, which are poisonous, mutagenic, genotoxic, and/or carcinogenic. Due to their ubiquitous occurrence and recalcitrance, PAHs-related pollution possesses significant public health and environmental concerns. Increasing the understanding of PAHs' negative impacts on ecosystems and human health has encouraged more researchers to focus on eliminating these pollutants from the environment. Nutrients available in the aqueous phase, the amount and type of microbes in the culture, and the PAHs' nature and molecular characteristics are the common factors influencing the microbial breakdown of PAHs. In recent decades, microbial community analyses, biochemical pathways, enzyme systems, gene organization, and genetic regulation related to PAH degradation have been intensively researched. Although xenobiotic-degrading microbes have a lot of potential for restoring the damaged ecosystems in a cost-effective and efficient manner, their role and strength to eliminate the refractory PAH compounds using innovative technologies are still to be explored. Recent analytical biochemistry and genetically engineered technologies have aided in improving the effectiveness of PAHs' breakdown by microorganisms, creating and developing advanced bioremediation techniques. Optimizing the key characteristics like the adsorption, bioavailability, and mass transfer of PAH boosts the microorganisms' bioremediation performance, especially in the natural aquatic water bodies. This review's primary goal is to provide an understanding of recent information about how PAHs are degraded and/or transformed in the aquatic environment by halophilic archaea, bacteria, algae, and fungi. Furthermore, the removal mechanisms of PAH in the marine/aquatic environment are discussed in terms of the recent systemic advancements in microbial degradation methodologies. The review outputs would assist in facilitating the development of new insights into PAH bioremediation.

Treatment of hazardous landfill leachate containing 1,4 dioxane by biochar-based photocatalysts in a solar photo-oxidation reactor.

This study investigates a combined photocatalytic and adsorption system to maximize the removal of 1,4 dioxane from hazardous landfill leachate (HLL). The production of transformation products was also investigated to obtain a comprehensive evaluation of the treatment system. Copper/iron doped zinc oxide (Cu-Fe-ZnO) was introduced to biochar to form a hybrid materials and used to treat HLL contaminated with 1,4 dioxane of 355.0 ± 11.7 mg/L. The Cu-Fe-ZnO/biochar removed 93.1 ± 8.7% of 1,4 dioxane at a dose of 0.6 g/L within 90 min, as compared with only 42.7 ± 3.3% by 1.2 g/L of bare biochar within 210 min. The Cu-Fe-ZnO/biochar degraded 1,4 dioxane into ethylene glycol, glycolic acid, and formic acid. The 1,4 dioxane removal mechanisms were investigated using the density functional theory, demonstrating that doping of ZnO with metal atoms (Cu-Fe) narrowed the bandgap from 3.307 eV to 2.736 eV. The enhanced photocatalytic activity of ZnO was also supported by the role of biochar in increasing the reactive species and adsorbing the pollutant molecules. The high degradation efficiency of 1,4 dioxane using small catalyst doses with short reaction times would reduce the treatment cost and improve the system's applicability for treating HLL and industrial effluents.

Promise of Real-World Evidence for Patient Centricity in Gulf Cooperation Council Countries: Call to Action.

Presently, Gulf Cooperation Council countries are lagging in the generation of real-world data and use of real-world evidence for patient-centered care compared with the global average. In a collaborative effort, experts from multiple domains of the healthcare environment from the Gulf Cooperation Council countries came together to present their views and recommended key action points for the generation of robust real-world data and leveraging real-world evidence in the countries. The opinions of the experts are presented, along with existing barriers to the effective generation of real-world evidence in the countries. The Gulf Cooperation Council countries are undergoing transformative changes paving the way for improved healthcare measures; however, the challenges in generating reliable, robust, accessible, and secure real-world evidence are persistent. Hence, ongoing public-private engagements, as well as collaborations between regulators, policymakers, healthcare professionals, insurance and pharmaceutical companies, and patients, are warranted. A few notable examples of real-world evidence studies highlighting the benefits of real-world evidence for gaining valuable insights into patient-centric decision making are also discussed. The actionable steps identified for successful real-world evidence generation would provide long-term, real-world evidence-based patient-centric benefits for the countries.

Engineered nanomedicines to overcome resistance of pancreatic cancer to immunotherapy.

Pancreatic cancer (PC) is a highly aggressive malignant type of cancer. Although immunotherapy has been successfully used for treatment of many cancer types, many challenges limit its success in PC. Therefore, nanomedicines were engineered to enhance the responsiveness of PC cells to immune checkpoint inhibitors (ICIs). In this review, we highlight recent advances in engineering nanomedicines to overcome PC immune resistance. Nanomedicines were used to increase the immunogenicity of PC cells, inactivate stromal cancer-associated fibroblasts (CAFs), enhance the antigen-presenting capacity of dendritic cells (DCs), reverse the highly immunosuppressive nature of the tumor microenvironment (TME), and, hence, improve the infiltration of cytotoxic T lymphocytes (CTLs), resulting in efficient antitumor immune responses.