Search Results (114)

Background: Rapid advances in biotechnology provide researchers with the opportunity to integrate omics profiles (genomics, epigenomics, transcriptomics, proteomics, etc.) with multiple phenotypes or experimental conditions. In cancers such as acute myeloid leukemia (AML), where combination therapies are standard of care, identifying genetic drivers of drug resistance requires evaluating how genes are associated with multiple drug response phenotypes. Statistical analyses associating omics profiles with multiple phenotypes yield multiple significance values and rankings for each of many genes. There is a great need to consolidate these multiple rankings into a consensus ranking to prioritize specific genes for detailed follow-up wet-lab or clinical studies. Methods/Results: Here, we evaluate the well-known Fisher’s method, the sum of squared z-statistics (SSz), and the recently published cellMCD method as tools for gene prioritization. In simulation studies, cellMCD showed very similar or highly superior performance to the widely used Fisher’s and SSz methods. These advantages were also observed in an example application involving a CRISPR drug screen of an acute myeloid leukemia cell line. Conclusions: In summary, our results indicate that cellMCD should be more widely used for prioritizing discoveries from multiple omic association studies. These methods are available as an R package on github. Full article

Background: To repurpose carbutamide (CBT), a discontinued sulfonylurea-class anti-diabetic drug, as an anti-inflammatory bowel disease (IBD) drug, CBT azo-linked with salicylic acid (CAA) was designed and synthesized as a colon-specific prodrug to co-release CBT and mesalazine (5-ASA) selectively in the large intestine. Methods: CAA exhibited reduced lipophilicity and decreased transintestinal transport compared to CBT, as shown in an ex vivo experiment using isolated rat jejunal segments. It also underwent cleavage into CBT and 5-ASA when incubated with cecal contents of rats. Additionally, oral administration of CAA and Sulfasalazine (SSZ), a colon-specific prodrug of 5-ASA currently used for IBD treatment, resulted in similar levels of 5-ASA accumulation in the rat cecal region. Results: In a dinitrobenzene sulfonic acid-triggered colitis model in rats, CAA produced a more pronounced improvement in colon injury and inflammation than SSZ. Furthermore, rectal co-administration of CBT and 5-ASA conferred enhanced protective outcomes compared to monotherapy with either agent alone, suggesting a combined anticolitic action. The two drugs also jointly suppressed valacyclovir uptake via peptide transporter 1 (PepT1) in the distal colon, supporting PepT1 as a target contributing to their combined anticolitic effect. Unlike CBT, which significantly reduced blood glucose following oral administration, equimolar administration of CAA did not alter glycemic levels, consistent with reduced systemic exposure to CBT. Conclusions: In conclusion, CAA functions as a colon-specific mutual prodrug that surpasses SSZ in anticolitic performance while minimizing hypoglycemia risk, thus facilitating the repurposing of CBT as a treatment for IBD. Full article

Introduction: In hemoglobinopathies, the amount of globin synthesis in hemoglobin (Hb) or its structure is altered. Clinical features are related to the rate and kind of structural aberrations. The heterozygous form of the Lepore syndrome resembles minor thalassemia both clinically and hematologically. On electrophoresis, abnormal Hb Lepore fractions are found at a rate of 5–15%, with a mildly higher percentage of HbF and lower HbA. In general, Hb Lepore heterozygotes are asymptomatic. Case presentation: A 32-year-old male was admitted to our hospital with complaints of pain and swelling in multiple large joints and high-grade fever for 11 days. His past history was unremarkable; one of his sisters had the β-thalassemia trait. On physical examination, he was moderately anemic, with mild hepatomegaly and normal spleen; both knees and ankles were tender and swollen. Laboratory showed mild microcytic hypochromic anemia with variables similar to the thalassemia trait and signs of inflammation with very high CRP, serum ferritin, and leukocytosis. Blood sugars were increased. Hb electrophoresis showed an abnormal pattern with mild elevation in HbS, normal Hb F, mild reduction in HbA, and high HbA2, compatible with heterozygosity for the Hb Lepore beta chain variant. He was initially diagnosed with diabetes (treated with insulin) and sepsis from unknown origin, but fever and joint pains did not respond to NSAIDs or antibiotics. He had very good response on high-dose methylprednisolone. Undifferentiated arthritis was diagnosed in the patient with Hb Lepore, and he was treated with oral prednisolone and sulfasalazine (SSZ). At follow up, the patient was doing well. He refused further investigations and did not allow testing on his family members. In summary: Hb Lepore is a rare hemoglobinopathy linked to thalassemia, which may manifest with musculoskeletal problems. Our patient with the Hb Lepore trait presented with undifferentiated polyarthritis and fever, but in our case, a causal relationship remains unclear. This is one of the first adult cases of Hb Lepore in Bangladesh and the first with arthritis of unknown origin. The prevalence of Hb Lepore in Bangladesh is unknown. Full article

Gas turbines operate at exhaust gas temperatures exceeding 500 °C. Vanadium-based catalysts encounter challenges in NH₃-SCR denitrification due to vanadium volatilization and titanium dioxide support phase transition at high temperatures. This restricts the effective denitrification temperature range to 300~400 °C, falling short of gas turbine denitrification requirements. Zeolite-supported catalysts, known for their high specific surface area, abundant acid sites, and stable framework structure, demonstrate superior catalytic activity and hydrothermal stability at high temperatures. This review synthesizes recent advancements in high-temperature catalysts utilizing ZSM-5, Beta, SSZ-13, and SAPO-34 zeolites as supports. It elucidates the interaction mechanisms between active components (e.g., transition metals Fe, Cu, W, rare earth elements) and zeolite supports. Furthermore, it examines variations in denitrification performance through the lens of the high-temperature NH₃-SCR reaction mechanism, offering valuable insights for high-temperature denitrification catalyst development. Full article

This work quantifies how varying the Na/OSDA ratio in the synthesis gel (at fixed total [OH] content) affects the formation of SSZ-39, its growth kinetics, and the composition of the products obtained. It was found that it is possible to make phase-pure SSZ-39 with Si/Al ratios varying from 6.3 to 10.7 with Na/OSDA ratios from 9.1 to 1.7 in the synthesis gel. Higher Na/OSDA ratios lead to faster crystallization, supporting the hypothesis that FAU dissolution is the rate-limiting step in SSZ-39 synthesis when FAU serves as the aluminum source. DFT modeling suggests that, in the presence of OSDA molecules, increased Na content lowers the energy penalty for placing Al atoms in close proximity, which may explain why higher NaOH/OSDA ratios experimentally yield lower Si:Al ratios. This work offers another way to control the framework composition and potentially impact the local structure of the SSZ-39 that is obtained. Cobalt titration was performed to probe the presence of so-called aluminum pairs in samples made with different Na/OSDA ratios. The cobalt uptake in the H-form products is consistently low and suggests that factors other than aluminum pairing, such as solution pH, could be important in influencing the cobalt uptake. Full article

The rational design of high-performance Cu-SSZ-13 catalysts with enhanced low-temperature activity represents a critical challenge for meeting stringent Euro VII emission standards in diesel aftertreatment systems. Elevating Cu loading can theoretically improve catalytic performance; however, one-time ion exchange using common CuSO₄ solution makes it hard to accomplish high Cu-ion contents. Herein, we demonstrate that the conventional ion-exchange method, adopting Cu(CH₃COO)₂ as precursor in NH₄-SSZ-13 zeolite with a low Si/Al ratio (≈6–7), can achieve higher Cu content while maintaining superior dispersion of active sites. Comprehensive characterizations reveal a dual incorporation mechanism: canonical Cu²⁺ ion exchange and unique adsorption of the [Cu(CH₃COO)]⁺ complex. In the latter case, the surface-adsorbed [Cu(CH₃COO)]⁺ ions form high-dispersion CuO_x species, while the framework-confined ones convert to active Z[Cu²⁺(OH)]⁺ ions. The Cu(CH₃COO)₂-exchanged Cu-SSZ-13 catalyst exhibits superior low-temperature SCR activity and hydrothermal stability to its CuSO₄-exchanged counterpart, making it particularly suitable for close-coupled SCR applications. Our findings provide fundamental insights into Cu speciation control in zeolites and present a scalable, industrially viable approach for manufacturing next-generation SCR catalysts capable of meeting future emission regulations. Full article

Selective catalytic reduction filter (SDPF) technology constitutes a critical methodology for controlling nitrogen oxide (NOx) and particulate matter emissions from light-duty diesel vehicles. A series of SDPFs with different sulfur poisoning times and concentrations were prepared using the worldwide harmonized light vehicles test cycle (WLTC). Bench testing revealed that sulfur poisoning diminished the catalyst’s NH₃ storage capacity, impaired the transient NOx reduction efficiency, and induced premature ammonia leakage. After multiple sulfur poisoning incidents, the NOx reduction performance stabilized. Higher SO₂ concentrations accelerated catalyst deactivation and hastened the attainment of this equilibrium state. The characterization results for the catalyst indicate that the catalyst accumulated the same sulfur content after tail gas poisoning with different sulfur concentrations and that sulfur existed in the form of SO₄²⁻. The sulfur species in low-sulfur-poisoning-concentration catalysts mainly included sulfur ammonia and sulfur copper species, while high-sulfur-poisoning-concentration catalysts contained a higher proportion of sulfur copper species. Neither species type significantly altered the zeolite coating’s crystalline structure. Sulfur ammonia species could easily lead to a significant decrease in the specific surface area of the catalyst, which could be decomposed at 500 °C to achieve NOx reduction performance regeneration. In contrast, sulfur copper species required higher decomposition temperatures (600 °C), achieving only partial regeneration. Full article

The urban heat island (UHI) effect and its associated extreme weather events have adverse impacts on human environment-coupled systems. However, the spatiotemporal variations in the UHI effect, as well as potential influencing factors, across climate zones remain poorly understood. This study explored how climate zones influenced the spatiotemporal variation in, trends in, and drivers of summer daytime surface UHI intensity (SUHII) in 220 Chinese cities located in five climate zones from 2000 to 2020. SUHII was quantified using MODIS land surface temperature (LST) data and remote sensing-derived urban built-up area masks were used to quantify SUHII. The Mann–Kendall test was applied to detect long-term SUHII trends, while Pearson correlation and stepwise multiple regression analyses were performed to identify key climatic and geographic drivers across different climate zones. The results indicated summer daytime SUHII values of 1.75 °C ± 1.19 °C, 1.74 °C ± 0.81 °C, 2.37 °C ± 0.75 °C, 2.14 °C ± 1.00 °C, and 2.36 °C ± 0.91 °C for the middle temperate zone (MTZ), south temperate zone (STZ), north subtropical zone (NSZ), middle subtropical zone (MSZ), and south subtropical zone (SSZ), respectively. In most cities, the SUHII increased significantly over time (p < 0.05). Pearson’s correlation analysis indicated that the enhanced vegetation index (EVI) and net radiation (NR) were moderately correlated with the SUHII in the MTZ, with correlation coefficients (r) of 0.465 and 0.42 (p < 0.05). Using a multivariate stepwise regression model, the relative contributions of various influencing factors to the UHI effect were quantified, explaining 27.1% to 57.2% of the variation across different climate zones. In particular, the economic vulnerability index and population density were the main factors affecting the SUHII in the MTZ and SSZ. Our findings support the development of policies aimed at mitigating the UHI effect by addressing the specific requirements of different climate zones to reduce. Full article

The selective catalytic reduction of NO_x with CH₄ (CH₄-SCR) holds the potential to simultaneously abate harmful NO_x and CH₄ greenhouse gases. In this study, a series of bimetallic M-In/H-SSZ-39 catalysts (where M represents Cr, Co, Ce, and Fe) were prepared via an ion exchange method and subsequently evaluated for their CH₄-SCR activity. The influences of the preparation parameters, including the metal ion concentration and calcination temperature, as well as the operating conditions, such as the CH₄/NO ratio, O₂ concentration, water vapor content, and gas hourly space velocity (GHSV), on the catalytic activity of the optimal Cr-In/H-SSZ-39 catalyst were meticulously examined. The results revealed that the Cr-In/H-SSZ-39 catalyst exhibited peak CH₄-SCR catalytic performance when the Cr(NO₃)₃ concentration was 0.0075 M, the In(NO₃)₃ concentration was 0.066 M, and the calcination temperature was 500 °C. Under optimal operating conditions, namely GHSV of 10,000 h⁻¹, 400 ppm NO, 800 ppm CH₄, 15 vol% O₂, and 6 vol% H₂O, the NO_x conversion rate reached 93.4%. To shed light on the excellent performance of Cr-In/H-SSZ-39 under humid conditions, a comparative analysis of the crystalline phase, chemical composition, pore structure, surface chemical state, surface acidity, and redox properties of Cr-In/H-SSZ-39 and In/H-SSZ-39 was conducted. The characterization results indicated that the incorporation of Cr into In/H-SSZ-39 enhanced its acidity and also facilitated the generation of InO⁺ active species, which promoted the oxidation of NO and the activation of CH₄, respectively. A synergistic effect was observed between Cr and In species, which significantly improved the redox properties of the catalyst. Consequently, the activated CH₄ could further interact with InO⁺ to produce carbon-containing intermediates such as HCOO⁻, which ultimately reacted with nitrate-based intermediates to yield N₂, CO₂, and H₂O. Full article

The Dehbid region, located in the southern part of the Sanandaj–Sirjan Zone (SSZ), is a significant iron oxide mining district with over 20 iron oxide deposits (IODs) and reserves of up to 50 million tons of iron oxide ores. The region features a NW–SE oriented ductile shear zone, parallel to the Zagros thrust zone, experienced significant deformation. Detailed structural studies indicate that the iron mineralization is primarily stratiform to stratabound and hosted in late Triassic to early Jurassic silicified dolomites and schists. These ore deposits consist of lenticular iron oxide orebodies and exhibit various structures and textures, including banded, laminated, folded, disseminated, and massive forms of magnetite and hematite. The Fe₂O₃ content in the mineralized layers varies from 30 to 91 wt%, whereas MnO has an average of 3.9 wt%. The trace elements are generally low, except for elevated concentrations of Cu (up to 4350 ppm) and Zn (up to 3270 ppm). Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) analysis of magnetite reveals high concentrations of Mg, Al, Si, Mn, Ti, Cu, and Zn, with significant depletion of elements such as Ga, Ge, As, and Nb. This study refutes the hypothesis of vein-like or hydrothermal genesis, providing evidence for a sedimentary origin based on the trace element geochemistry of magnetite and LA-ICP-MS geochemical data. The Dehbid banded iron ores (BIOs) are thought to have formed under geodynamic conditions similar to those of BIOs in back-arc tectonic settings. The combination of anoxic conditions, submarine hydrothermal iron fluxes, and redox fluctuations is essential for the formation of these deposits, suggesting that similar iron–manganese deposits can form during the Phanerozoic under specific geodynamic and oceanographic conditions, particularly in tectonically active back-arc environments. Full article

With accelerating climate change and urbanization, regional carbon balance faces increasing uncertainty. Terrestrial carbon sinks play a crucial role in advancing China’s sustainable development under the dual-carbon strategy. This study quantitatively modeled China’s terrestrial carbon sink capacity and analyzed the multidimensional relationships between impact factors and carbon sinks. After preprocessing multi-source raster data, we introduced kernel normalized the difference vegetation index (kNDVI) to the Carnegie–Ames–Stanford approach (CASA) model, together with a heterotrophic respiration (R_h) empirical equation, to simulate pixel-level net ecosystem productivity (NEP) across China. A light gradient-boosting machine (LightGBM) model, optimized via Bayesian algorithms, was trained to regress NEP drivers, categorized into atmospheric components (O₃, NO₂, and SO₂) and subsurface properties (a digital elevation model (DEM), enhanced vegetation index (EVI), soil moisture (SM)), and human activities (land use/cover change (LUCC), POP, gross domestic product (GDP)). Shapley Additive Explanation (SHAP) values were used for model interpretation. The results reveal significant spatial heterogeneity in NEP across geographic and climatic contexts. The pixel-level mean and total NEP in China were 268.588 gC/m²/yr and 2.541 PgC/yr, respectively. The north tropical zone (NRZ) exhibited the highest average NEP (828.631 gC/m²/yr), while the middle subtropical zone (MSZ) and south subtropical zone (SSZ) demonstrated the most stable NEP distributions. LightGBM achieved high simulation accuracy, further enhanced by Bayesian optimization. SHAP analysis identified EVI as the most influential factor, followed by SM, NO₂, DEM, and POP. Additionally, LightGBM effectively captured nonlinear relationships and variable interactions. Full article

Selective catalytic reduction of NO_x with H₂ (H₂-SCR) is crucial for eliminating NO_x emissions from hydrogen internal combustion engines (H₂-ICE). Although 1 wt.% Pt/SSZ-13 (Pt/SZ) is a promising H₂-SCR catalyst, it faces challenges such as a narrow operating window and low N₂ selectivity. Herein, the effects of WO₃ on improving the H₂-SCR performance of Pt/SZ was investigated. Results showed that incorporating 5 wt.% WO₃ significantly widened the temperature window for 80% NO_x conversion and enhanced N₂ selectivity at 90–180 °C. Several characterizations revealed that electrons transfer from W to Pt, so more active Pt⁰ species were formed on 1 wt.% Pt-5 wt.% W/SZ (Pt-5W/SZ). In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) analysis indicated that more active monodentate nitrates, nitrites, and NH₄⁺ species were generated on Pt-5W/SZ, which are key intermediates for N₂ formation. Consequently, the temperature windows for NO_x conversion (over 80%) and N₂ selectivity (over 70%) were widened by 65 °C and 66 °C, respectively. This work provides insights into the developing H₂-SCR catalysts with broader operating windows and higher N₂ selectivity. Full article

Eye Movement Desensitization and Reprocessing (EMDR) was recognized by the World Health Organization in 2013 as an evidence-based therapy for post-traumatic stress disorder (PTSD) and found to be effective for depression. Since then, EMDR has evolved into a personalized treatment focusing on stabilizing the physiological and psychological processes to alleviate symptoms of depression and stress. However, optimized parameters for video stimuli, such as speed (s_sp), distance (d), and size (s_sz), are not yet well defined in EMDR protocols. This study addresses this gap by employing an artificial neural network (ANN) methodology based on Francine Shapiro’s Adaptive Information Processing (AIP) model. The ANN was used to determine ideal values for video stimuli parameters, developing an integrated model to enhance EMDR outcomes. Of the 2860 ANN-modeled combinations, stimulus settings of 1.8 Hz speed, 70-pixel size, and 1440-pixel distance achieved the highest Predicted Effectiveness Score (PES) of 98.7%. An EMDR field test with electroencephalography (EEG) was conducted to assess the optimized video stimuli’s efficacy. Further, 16 participants, selected from a sample of 56 meeting CES-D depression criteria, were evaluated, and the top 50 PES values were selected for further analysis. EEG results indicated a 12.31% increase in effectiveness, showing a reduction in right frontal lobe beta waves. These findings highlight the technical advancements and therapeutic potential of the proposed ANN-optimized EMDR stimuli, demonstrating statistically significant improvements over traditional methods. Full article

Background/Objectives: In addition to oncological applications, poly(ADP-ribose) polymerase (PARP) inhibitors have potential as anti-inflammatory agents. Colon-targeted delivery of PARP inhibitors has been evaluated as a pharmaceutical strategy to enhance their safety and therapeutic efficacy against gut inflammation. Methods: Colon-targeted PARP inhibitors 5-aminoisoquinoline (5-AIQ) and 3-aminobenzamide (3-AB) were designed and synthesized by azo coupling with salicylic acid (SA), yielding 5-AIQ azo-linked with SA (AQSA) and 3-AB azo-linked with SA (ABSA). Additional conjugation of AQSA with acidic amino acids yielded glutamic acid-conjugated AQSA (AQSA-Glu) and aspartic acid-conjugated AQSA, which further increased the hydrophilicity of AQSA. Results: The distribution coefficients of PARP inhibitors were lowered by chemical modifications, which correlated well with drug permeability via the Caco-2 cell monolayer. All derivatives were effectively converted to their corresponding PARP inhibitors in the cecal contents. Compared with observations in the oral administration of PARP inhibitors, AQSA-Glu and ABSA resulted in the accumulation of much greater amounts of each PARP inhibitor in the cecum. ABSA accumulated mesalazine (5-ASA) in the cecum to a similar extent as sulfasalazine (SSZ), a colon-targeted 5-ASA prodrug. In the DNBS-induced rat colitis model, AQSA-Glu enhanced the anticolitic potency of 5-AIQ. Furthermore, ABSA was more effective against rat colitis than SSZ or AQSA-Glu, and the anticolitic effects of AQSA-Glu were augmented by combined treatment with a colon-targeted 5-ASA prodrug. In addition, the colon-targeted delivery of PARP inhibitors substantially reduced their systemic absorption. Conclusions: Colon-targeted PARP inhibitors may improve the therapeutic and toxicological properties of inhibitors and synergize the anticolitic effects of 5-ASA. Full article

Serpentinites make up one of the most significant rock units associated with primary suture zones throughout the ophiolite sequence of the Arabian–Nubian Shield. Wadi Sodmein serpentinites (WSSs) represent dismembered parts of the oceanic supra-subduction system in the central Eastern Desert of Egypt. In this context, we present whole-rock major, trace, and rare earth elements (REE) analyses, as well as mineral chemical data, to constrain the petrogenesis and geotectonic setting of WSS. Antigorite represents the main serpentine mineral with minor amounts of chrysotile. The predominance of antigorite implies the formation of WSS under prograde metamorphism, similar to typical metamorphic peridotites of harzburgitic protolith compositions. The chemistry of serpentinites points to their refractory composition with notably low Al₂O₃, CaO contents, and high Mg# (90–92), indicating their origin from depleted supra-subduction zone harzburgites that likely formed in a forearc mantle wedge setting due to high degrees of hydrous partial melting and emplaced owing to the collision of the intra–oceanic arc with Meatiq Gneisses. Spinels of WSS generally exhibit pristine compositions that resemble those of residual mantle peridotites and their Cr# (0.625–0.71) and TiO₂ contents (<0.05 wt%) similar to forearc peridotite spinels. Moreover, WSS demonstrates a significant excess of fluid mobile elements (e.g., Th, U, Pb), compared to high-field strength elements (e.g., Ti, Zr, Nb, Ta), implying an interaction between mantle peridotites and fluids derived from the oceanic subducted-slab. The distinct U-shaped REE patterns coupled with high Cr# of spinel from WSS reflect their evolution from mantle wedge harzburgite protolith that underwent extensive melt extraction and re-fertilized locally. Full article