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Cost-effective CO2 adsorbents are gaining increasing attention as viable solutions for mitigating climate change. In this study, composites were synthesized by electrochemically combining the post-gasification residue of Macadamia nut shell with copper benzene-1,3,5-tricarboxylate (CuBTC). Among the different composites synthesized, the ratio of 1:1 between biochar and CuBTC (B 1:1) demonstrated the highest CO2 adsorption capacity. Under controlled laboratory conditions (0°C, 1 bar, without the influence of ambient moisture or CO2 diffusion limitations), B 1:1 achieved a CO2 adsorption capacity of 9.8 mmol/g, while under industrial-like conditions (25°C, 1 bar, taking into account the impact of ambient moisture and CO2 diffusion limitations within a bed of adsorbent), it reached 6.2 mmol/g. These values surpassed those reported for various advanced CO2 adsorbents investigated in previous studies. The superior performance of the B 1:1 composite can be attributed to the optimization of the number of active sites, porosity, and the preservation of the full physical and chemical surface properties of both parent materials. Furthermore, the composite exhibited a notable CO2/N2 selectivity and improved stability under moisture conditions. These favorable characteristics make B 1:1 a promising candidate for industrial applications.

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BACKGROUND: We aimed to (1) report updated estimates of direct healthcare costs for people living with MS (pwMS), (2) contrast costs to a control population and (3) explore differences between disability levels among pwMS. METHODS: Administrative data were used to identify adult pwMS (MS cohort) and without (control cohort) in Alberta, Canada; disability level (based on the Expanded Disability Status Scale) among pwMS was estimated. One- and two-part generalized linear models with gamma distribution were used to estimate the incremental direct healthcare cost (2021 $CDN) of MS during a 1-year observation period. RESULTS: Adjusting for confounders, the total healthcare cost ratio was higher in the MS cohort (n = 13,089) versus control (n = 150,080) (5.24 [95% CI: 5.08, 5.41]) with a predicted incremental cost of $15,016 (95% CI: $14,497, $15,535) per person-year. Among the MS cohort, total predicted direct healthcare costs were higher with greater disability, $14,430 (95% CI: $13,980, $14,880) to $58,697 ($51,514, $65,879) per person-year in mild and severe disability, respectively. The primary health resource cost component shifted from disease-modifying therapies in mild disability to supportive care in moderate and severe disability. CONCLUSION: Adult pwMS had greater direct healthcare costs than those without. Extrapolating to the population level (where 14,485 adult pwMS were identified in the study), it is estimated that $218 million per year in healthcare costs may be attributable to MS in Alberta. The significantly larger economic impact associated with greater disability underscores the importance of preventing or delaying disease progression and functional impairment in MS.

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ABSTRACT: Legionella spp. is an underreported cause of Community Acquired pneumonia that affects significant population specially in urban areas and its prevalence is on an increasing trend. The routine practice of testing for urinary antigen of Legionella in all suspected cases of pneumonia is prevalent is resource rich western countries. Although several studies have shown no distinct advantage of performing routine urinary antigen testing, this practice continues to be preferred by clinicians. In this viewpoint, we have discussed the advantages and disadvantages of urinary antigen testing, its relevance in current practice and its impact on clinical outcomes.

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Green silver nanoparticles (AgNPs) were synthesized using natural extracts as reducing agents and were firstly applied as co-catalysts in low-intensity-visible-light driven photocatalytic hydrogen production (PH2P), which a solution for green energy sources and independence from fossil fuels. The as-prepared AgNPs possessed size in a few tens nanometers and exhibited surface plasmon resonance (SPR) effects in the 310-560 nm region. Depositing AgNPs on g-C3N4 nanosheets broadened the visible absorption range, reduced electron-hole recombination, and increased electronic communication at the interface. g-C3N4/Ag demonstrated high PH2P efficiency, stability over three consecutive cycles, and a rapidly rising photocurrent under low-intensity visible light irradiation, although these features were not observed in g-C3N4 alone. The H2 evolution of g-C3N4/Ag_CC (CC: Cinnamomum camphora), g-C3N4/Ag_GT (GT: green tea), and g-C3N4/Ag_PP (PP: pomelo peels) reached 252.6, 125.3 and 92.0 µmol g-1 at 180 min at the first cycle, respectively. Among them, g-C3N4/Ag_CC showed the highest photocatalytic activity, which may be attributed to the superior morphology, optical properties of AgNPs_CC, and efficient electron transfer from g-C3N4 to AgNPs_CC. The SPR effect and Schottky barriers formed at the interface could contribute to enhancing the overall efficiency of the heterojunction photocatalysts. The results highlighted a crucial advancement toward H2 production under low-intensity visible-light irradiation.

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We perform large-scale atomistic simulations of a system containing 12 × 106 atoms, comprising an oxygen gas-filled bubble immersed in water, to understand the stability and cavitation induced by ultrasound. First, we propose a method to construct a bubble/water system. For a given bubble radius, the pressure inside the bubble is estimated using the Young-Laplace equation. Then, this pressure is used as a reference for a constant temperature, constant pressure simulation of an oxygen system, enabling us to extract a sphere of oxygen gas and place it into a cavity within an equilibrated water box. This ensures that the Young-Laplace equation is satisfied and the bubble is stable in water. Second, this stable bubble is used for ultrasound-induced cavitation simulations. We demonstrate that under weak ultrasound excitation, the bubble undergoes stable cavitation, revealing various fluid velocity patterns, including the first-order velocity field and microstreaming. These fluid patterns emerge around the bubble on a nanometer scale within a few nanoseconds, a phenomenon challenging to observe experimentally. With stronger ultrasound intensities, the bubble expands significantly and then collapses violently. The gas core of the collapsed bubble, measuring 3-4 nm, exhibits starfish shapes with temperatures around 1500 K and pressures around 6000 bar. The simulation results are compared with those from Rayleigh-Plesset equation modeling, showing good agreement. Our simulations provide insights into the stability and cavitation of nanosized bubbles.

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Three generations of tyrosine kinase inhibitors (TKI) have been approved for anaplastic lymphoma kinase (ALK) fusion-positive non-small cell lung cancer. However, none address the combined need for broad resistance coverage, brain activity, and avoidance of clinically dose-limiting TRK inhibition. NVL-655 is a rationally designed TKI with >50-fold selectivity for ALK over 96% of the kinome tested. In vitro, NVL-655 inhibits diverse ALK fusions, activating alterations, and resistance mutations, showing ≥100-fold improved potency against ALKG1202R single and compound mutations over approved ALK TKIs. In vivo, it induces regression across 12 tumor models, including intracranial and patient-derived xenografts. NVL-655 inhibits ALK over TRK with 22-fold to >874-fold selectivity. These preclinical findings are supported by three case studies from an ongoing first-in-human phase I/II trial of NVL-655 which demonstrate preliminary proof-of-concept clinical activity in heavily pretreated patients with ALK fusion-positive non-small cell lung cancer, including in patients with brain metastases and single or compound ALK resistance mutations. Significance: By combining broad activity against single and compound ALK resistance mutations, brain penetrance, and selectivity, NVL-655 addresses key limitations of currently approved ALK inhibitors and has the potential to represent a distinct advancement as a fourth-generation inhibitor for patients with ALK-driven cancers.

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The current radiation dose estimates used in medical imaging, radiation oncology or environmental assessments are not entirely accurate from a fundamental physics perspective, let alone for biological consequences. The "one cloth fits all" approach of radiation-matter interactions cannot assess the effects of interactions of the same species of radiation of different energies on the same isotope of an element. Preliminary steps to set the radiation dosimetry in the right direction are suggested.

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Structure-based virtual screening is a key tool in early drug discovery, with growing interest in the screening of multi-billion chemical compound libraries. However, the success of virtual screening crucially depends on the accuracy of the binding pose and binding affinity predicted by computational docking. Here we develop a highly accurate structure-based virtual screen method, RosettaVS, for predicting docking poses and binding affinities. Our approach outperforms other state-of-the-art methods on a wide range of benchmarks, partially due to our ability to model receptor flexibility. We incorporate this into a new open-source artificial intelligence accelerated virtual screening platform for drug discovery. Using this platform, we screen multi-billion compound libraries against two unrelated targets, a ubiquitin ligase target KLHDC2 and the human voltage-gated sodium channel NaV1.7. For both targets, we discover hit compounds, including seven hits (14% hit rate) to KLHDC2 and four hits (44% hit rate) to NaV1.7, all with single digit micromolar binding affinities. Screening in both cases is completed in less than seven days. Finally, a high resolution X-ray crystallographic structure validates the predicted docking pose for the KLHDC2 ligand complex, demonstrating the effectiveness of our method in lead discovery.

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The potential alternative of exploring the development of nanocomposites through a single-molecule approach, such as combining chitosan nanoparticles (ChiNP) with chitosan (Chi), remains to be investigated. To maintain the insolubility of the ChiNP filler in the system, the protonation of weakly basic amino groups necessitates the pH of the coating solution above the pKa (6-6.5). This study aimed to evaluate the biofunctional properties improvements of Chi coatings incorporated with ChiNP as filler agents. The coating film forming solution comprised of 0.8 % Chi combined with varying concentrations (0 %, 0.1 %, 0.5 %, and 1 %) of ChiNP. The morphology of ChiNP was characterized via atomic force spectroscopy (AFM). Incorporating the ChiNP (1 %) significantly enhanced antifungal efficacy, i.e., an 88.28 % reduction in fungal activity compared with the control group, and a 65 % reduction compared with pure Chi against Botrytis cinerea. The incorporation of ChiNP improved the ultraviolet and visible light wavelengths, water vapor permeability, hydrophobicity, and thermal properties. Scanning electron microscopy and AFM were performed to assess the surface and internal microstructures of the coating. The findings of this study suggested that the nanocomposite coatings herein presented is potential for use in active packaging, especially in the context of preserving fresh fruit products.

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The increase in hydro dams in the Mekong River amidst the prevalence of multidrug-resistant malaria in Cambodia has raised concerns about global public health. Political conflicts during Covid-19 pandemic led cross-border movements of malaria cases from Myanmar and caused health care burden in Thailand. While previous publications used climatic indicators for predicting mosquito-borne diseases, this research used globally recognizable World Bank indicators to find the most impactful indicators related with malaria and shed light on the predictability of mosquito-borne diseases. The World Bank datasets of the World Development Indicators and Climate Change Knowledge Portal contain 1494 time series indicators. They were stepwise screened by Pearson and Distance correlation. The sets of five and four contain respectively 19 and 149 indicators highly correlated with malaria incidence which were found similarly among five and four GMS countries. Living areas, ages, career, income, technology accessibility, infrastructural facilities, unclean fuel use, tobacco smoking, and health care deficiency have affected malaria incidence. Tonle Sap Lake, the largest freshwater lake in Southeast Asia, could contribute to the larval habitat. Seven groups of indicator topics containing 92 indicators with not-null datapoints were analyzed by regression models, including Multiple Linear, Ridge, Lasso, and Elastic Net models to choose 7 crucial features for malaria prediction via Long Short Time Memory network. The indicator of people using at least basic sanitation services and people practicing open defecation were health factors had most impacts on regression models. Malaria incidence could be predicted by one indicator to reach the optimal mean absolute error which was lower than 10 malaria cases (per 1,000 population at risk) in the Long Short Time Memory model. However, public health crises caused by political problems should be analyzed by political indexes for more precise predictions.

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Hexagonal boron nitride (BN), a well-known member of 2D materials, has a structure similar to graphene and is often referred to as white graphene. Despite its unique physical and chemical properties for energy storage applications, there have been very few studies on how BN stores anion carriers. Herein, the hybrid architecture and anion storage mechanism of BN nanosheets for high-performance hybrid energy storage full cells based on dual-ion and Zinc (Zn) alkaline systems is demonstrated. The chemical bonding between BN and reduced graphene oxide (rGO) is attributed to the formation of the heterointerface, which facilitates the charge transfer kinetics during an OH storing process. Based on the reversible surface redox reaction of BN and rGO hybrid (BN@rGO) confirmed by computational and spectroscopic analyses, the BN@rGO electrode is applied to both Na and OH dual-ion and Zn alkaline full cells. In the dual-ion system, Ti3C2‖BN@rGO full cells extended the operating voltage range up to 1.7 V, delivering a cell capacity of 49.4 mAh g-1 at 1000 mA g-1 and retaining 80% of its initial capacity after 40 000 cycles. In the Zn alkaline system, Zn‖BN@rGO full cells achieved a cell capacity of 58.1 mAh g-1 at 1000 mA g-1 and retained 80% capacity over 90 000 cycles.

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The islet amyloid polypeptide (IAPP), also known as amylin, is a hormone playing key physiological roles. However, its aggregation and deposition in the pancreatic islets are associated with type 2 diabetes. While this peptide adopts mainly a random coil structure in solution, its secondary conformational conversion into α-helix represents a critical step for receptor activation and contributes to amyloid formation and associated cytotoxicity. Considering the large conformational landscape and high amyloidogenicity of the peptide, as well as the complexity of the self-assembly process, it is challenging to delineate the delicate interplay between helical folding, peptide aggregation, and receptor activation. In the present study, we probed the roles of helical folding on the function-toxicity duality of IAPP by restricting its conformational ensemble through side chain-to-side chain stapling via azide-alkyne cycloaddition. Intramolecular macrocyclization (i; i + 4) constrained IAPP into α-helix and inhibited its aggregation into amyloid fibrils. These helical derivatives slowed down the self-assembly of unmodified IAPP. Site-specific macrocyclization modulated the capacity of IAPP to perturb lipid bilayers and cell plasma membrane and reduced, or even fully inhibited, the cytotoxicity associated with aggregation. Furthermore, the α-helical IAPP analogs showed moderate to high potency toward cognate G protein-coupled receptors. Overall, these results indicate that macrocyclization represents a promising strategy to protect an amyloidogenic peptide hormone from aggregation and associated toxicity, while maintaining high receptor activity.

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OBJECTIVE: To investigate Vietnamese people's knowledge, attitudes, and experience in purchasing medicines and functional foods online. METHODS: Via an online survey, the data of 1,070 participants were collected, including their general characteristics, Internet use, previous experience, knowledge, and attitudes towards purchasing medicines/functional foods online. Factors associated with their knowledge and attitudes were identified via multivariate linear regression models. RESULTS: During 2022-2023, about 97.2% of participants used the Internet to seek health information (self-diagnosis: 65.0%, self-medication: 72.6%). Roughly 52.8% bought medicines and/or functional foods online. Among 565 buyers, 41.8% felt satisfied. Only 19.9% understood that selling medicines online was illegal in Vietnam. The main benefits of purchasing medicines/functional foods online that many people agreed on included convenience (87.1%), freedom from location (84.8%), and being able to order/buy products after opening hours (84.7%). Many people felt worried about the ability to buy counterfeit or substandard products (87.7%), inaccurate product information (85.0%), the lack of supervision of the authorities (83.7%), and increasing risks of drug abuse, self-medication, and treatment non-adherence (82.5%). Roughly 84.3% found distinguishing between legal and illegal online pharmacies difficult. Participants' average knowledge and attitude scores were 6.514 ± 2.461 (range: 0-16) and 89.330 ± 13.720 (range: 23-115), respectively. The main factors associated with people's knowledge and attitudes towards purchasing these products online included their frequency of Internet use, seeking health information online for self-medication, feeling satisfied with previous experience, and having at least one chronic disease. CONCLUSIONS: Many Vietnamese people's knowledge about purchasing medicines/functional foods online was limited. With the increasing need for online shopping, enhancing their knowledge is paramount. In the forthcoming years, when the Ministry of Health and relevant authorities publish legal documents and enact laws involving online pharmacies and trading medicines on the Internet, ways to recognize licensed online pharmacies must be widely propagated and disseminated in the community.

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BACKGROUND: Multiple sclerosis (MS) is a chronic neurological condition and the leading cause of non-traumatic disability in young adults. MS pathogenesis leads to the death of oligodendrocytes, demyelination, and progressive central nervous system neurodegeneration. Endogenous remyelination occurs in people with MS (PwMS) but is insufficient to repair the damage. Our preclinical studies in mice indicate that endogenous remyelination can be supported by the delivery of repetitive transcranial magnetic stimulation (rTMS). Our phase I trial concluded that 20 sessions of rTMS, delivered over 5 weeks, are safe and feasible for PwMS. This phase II trial aims to investigate the safety and preliminary efficacy of rTMS for PwMS. METHODS: Participants must be aged 18-65 years, diagnosed with MS by a neurologist, stable and relapse free for 6 months, have an Extended Disability Status Scale (EDSS) between 1.5 and 6 (inclusive), willing to travel to a study site every weekday for 4 consecutive weeks, and able to provide informed consent and access the internet. Participants from multiple centres will be randomised 2:1 (rTMS to sham) stratified by sex. The intervention will be delivered with a Magstim Rapid2 stimulator device and circular 90-mm coil or MagVenture MagPro stimulator device with C100 circular coil, positioned to stimulate a broad area including frontal and parietal cortices. For the rTMS group, pulse intensity will be set at 18% (MagVenture) or 25% (Magstim) of maximum stimulator output (MSO), and rTMS applied as intermittent theta burst stimulation (iTBS) (~ 3 min per side; 600 pulses). For the sham group, the procedure will be the same, but the intensity is set at 0%. Each participant will attend 20 intervention sessions over a maximum of 5 weeks. Outcome measures include MS Functional Composite Score (primary), Fatigue Severity Scale, Hospital Anxiety and Depression Scale, Quality of Life, and Pittsburgh Sleep Quality Index/Numeric Rating Scale and adverse events (secondary) and advanced MRI metrics (tertiary). Outcomes will be measured at baseline and after completing the intervention. DISCUSSION: This study will determine if rTMS can improve functional outcomes or other MS symptoms and determine whether rTMS has the potential to promote remyelination in PwMS. TRIAL REGISTRATION: Registered with Australian New Zealand Clinical Trials Registry, 20 January 2022; ACTRN12622000064707.

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Generalized lymphangiomatosis (GLA) is a very rare condition in adults, characterized by diffused proliferation of lymphatic vessels that requires differential diagnosis from other vascular disorders such as cavernous or capillary hemangioma. This is because of overlapping characteristics on histopathological examination. Therefore, imaging features such as CT and MRI are useful to evaluate morphological characteristics, location, and the extent of the spread as well as differential diagnosis with other pathologies. We report a case of a 22-year-old female patient with left hemothorax after thoracoscopic sympathectomy for the treatment of hand sweating. The patient underwent drainage and cleaning of the left pleura. Chest computed tomography and lumbar spine magnetic resonance imaging showed multiple fat infiltration foci of the lumbar spine and pelvis. A wing bone biopsy of the pelvis was initially performed for the diagnosis of chronic osteomyelitis. Afterwards, the patient continued to have pleural drainage and developed hemothorax and chylothorax, amounting to 3000 mL. The chest tube was blocked with a mixture of biological glue and lipiodol (2 mL of glue, ratio of glue to lipiodol: 1:4) and a 3 i-ED coil complex. After the intervention, the pleural fluid decreased; the left pleural fluid was still 15 mm thick, and the amount of fluid drained after 1 week was 100 mL. Aspiration of the chest wall lesion showed fluid rich in fat droplets. Combined with the results of lumbar spine magnetic resonance imaging and the old biopsy, this was consistent with generalized lymphangiomatosis.

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Background Septic shock remains a leading cause of mortality in children. The lactate/albumin ratio (LAR) has emerged as a potential prognostic marker for mortality in septic shock, yet most existing research focuses on adults, with limited data available for pediatric populations, particularly in Vietnam. Objectives This study aims to evaluate the prognostic utility of the LAR in predicting 28-day mortality among children aged two months to 15 years with septic shock in Vietnam. Methods We conducted a prospective cohort study involving children diagnosed with septic shock at the largest pediatric intensive care unit (PICU) in the Mekong Delta, Vietnam, from July 2022 to June 2024. Clinical and laboratory parameters, including lactate and albumin levels, were measured at the time of septic shock diagnosis. Patients were followed for 28 days, with outcomes categorized as either survival or mortality. The prognostic performance of LAR was assessed through its discrimination and calibration capabilities. Results The 28-day mortality rate was 63.4%. LAR was significantly higher in non-survivors compared to survivors (p < 0.001). The area under the receiver operating characteristic curve (AUROC) for LAR was 0.91, indicating superior discriminatory power compared to lactate alone and comparable to albumin. Using a Youden index-derived cut-off of 1.84, LAR demonstrated a sensitivity of 84.6% and a specificity of 80%. Kaplan-Meier analysis and log-rank testing revealed significantly lower survival probabilities in children with LAR ≥1.84 (p < 0.05). The Hosmer-Lemeshow test confirmed good calibration of LAR in mortality prediction (p > 0.05). Conclusion The lactate/albumin ratio exhibits excellent discriminatory and calibration properties, making it a valuable tool for predicting 28-day mortality in pediatric septic shock. This ratio should be considered for routine use in clinical practice to improve prognostic assessments in this vulnerable population.

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Background: Multiple Organ Dysfunction Syndrome (MODS) is a complex medical condition characterised by dysfunction across multiple organs. With limited information available on mortality prediction in the paediatric population, particularly in low-middle income countries, this study evaluates the mortality predicting capabilities of lactate, D-dimer, and their combination. Methods: This prospective study involved paediatric patients admitted to the paediatric intensive care unit (PICU) of the largest central children's hospital in the Mekong Delta region, Vietnam, from 2019 to 2021. The discriminative ability and calibration of both individual and combined tests were assessed using the receiver operating characteristic (ROC) curves and the Hosmer-Lemeshow goodness-of-fit test. Results: Among the patients studied, 63.1% did not survive. Lactate and D-dimer concentrations were significantly higher in the non-survivor group (P < 0.001). The area under the curve (AUC) values for lactate, D-dimer and the combined lactate-D-dimer test were 0.742, 0.775 and 0.804, respectively, with the combination showing the highest AUC value, though without statistical significance. Specific thresholds for lactate, D-dimer and the combination yielded sensitivities of 75.5%, 71.7%, and 66.0%, respectively. All three tests showed no statistically significant differences between observed and predicted mortality in the Hosmer-Lemeshow test (all P-values > 0.05). Conclusion: Lactate and D-dimer levels showed a significant association with mortality, along with good discrimination and calibration abilities. These results highlight the utility of lactate and D-dimer as effective predictors in paediatric MODS, particularly in resource-limited settings, and their role in improving patient outcomes.

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Rice-shrimp rotation systems are one of the widespread farming practices in the Vietnamese Mekong Delta coastal areas. However, greenhouse gas (GHG) emissions in the system have remained unclear. This study aimed to examine methane (CH4) and nitrous oxide (N2O) emissions from the system, including (i) land-based versus high-density polyethylene-lined (HDPE) nursery ponds and (ii) conventional versus improved grow-out ponds inoculated with effective microorganisms (EM) bioproducts. The results showed that CH4 flux in land-based and HDPE-lined nursery ponds were 1.04 and 0.25 mgCH4 m-2 h-1, respectively, while the N2O flux was 8.37 and 6.62 µgN2O m-2 h-1, respectively. Global warming potential (GWP) from land-based nursery ponds (18.3 g CO2eq m-2) was approximately 3 folds higher than that of the HDPE-lined nursery pond (6.1 g CO2eq m-2). Similarly, the mean CH4 and N2O fluxes were 15.84 mg CH4 m-2 h-1 and 7.17 µg N2O m-2 h-1 for the conventional ponds, and 10.51 mg CH4 m-2 h-1 and 7.72 µg N2O m-2 h-1 for the improved grow-out ponds. Conventional practices (2388 g CO2eq m-2) had a higher 1.5-fold GWP compared to the improved grow-out pond (1635 g CO2eq m-2). The continuation of the land-based nursery pond and conventional aquacultural farming practices increase CH4 emission and GWP, while applying HDPE-lined nursery ponds combined with improved grow-out ponds could be a promising approach for reducing GHG emissions in rice-shrimp rotation systems. This study recommends further works in the rice-shrimp rotation systems, including (i) an examination of the effects of remaining rice stubbles in the platform on the availability of TOC levels and GHG emissions and (ii) ameliorating dissolved oxygen (DO) concentration on the effectiveness of GHG emission reduction.

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Cancer genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex including SMARCA4 in non-small cell lung cancer with a frequency of up to 33% in advanced stage disease, making it the most frequently mutated complex in lung cancer. We and others have identified SMARCA2 to be synthetic lethal to SMARCA4, indicating SMARCA2 is a high value therapeutic target. Here, we disclose the discovery and characterization of potent, selective and orally bioavailable Cereblon-based SMARCA2 PROTACs. Biochemically, YDR1 and YD54 are potent SMARCA2 degraders with an average DC 50 of 7.7nM and 3.5nM respectively in SMARCA4 mutant lung cancer cells. Phenotypically, both YDR1 and YD54 selectively inhibited growth of SMARCA4 mutant cancer cells. Further, we showed anti-tumor growth inhibitory activity of YDR1 and YD54 in SMARCA4 mutant xenograft models of lung cancer. Finally, we show that YDR1 and YD54 synergize with the KRAS G12C inhibitor sotorasib to inhibit growth of SMARCA4 and KRAS G12C co-mutant lung cancer cells. These findings provide additional evidence for the utility of single agent or combination regimens containing SMARCA2 PROTACs as synthetic lethal therapeutics against SMARCA4 mutant cancers.