MREDTA: A BERT and transformer-based molecular representation encoder for predicting drug-target binding affinity.

Drug-target binding affinity (DTA) prediction is vital for drug repositioning. The accuracy and generalizability of DTA models remain a major challenge. Here, we develop a model composed of BERT-Trans Block, Multi-Trans Block, and DTI Learning modules, referred to as Molecular Representation Encoder-based DTA prediction (MREDTA). MREDTA has three advantages: (1) extraction of both local and global molecular features simultaneously through skip connections; (2) improved sensitivity to molecular structures through the Multi-Trans Block; (3) enhanced generalizability through the introduction of BERT. Compared with 12 advanced models, benchmark testing of KIBA and Davis datasets demonstrated optimal performance of MREDTA. In case study, we applied MREDTA to 2034 FDA-approved drugs for treating non-small-cell lung cancer (NSCLC), all of which act on mutant EGFRT790M protein. The corresponding molecular docking results demonstrated the robustness of MREDTA.

Prognostic impact of DTA mutation and co-occurring mutations in patients with myelodysplastic syndrome.

OBJECTIVE: To evaluate the frequency and prognostic significance of DTA (DNMT3A、TET2、ASXL1) gene mutation and co-occurring mutations in patients with myelodysplastic syndrome (MDS). METHODS: The clinical data of 102 newly diagnosed MDS patients who accepted Next Generation Sequencing (NGS) was retrospectively analyzed. According to whether the patients had DTA gene mutation, the patients were divided into DTA mutated (DTA-mut) group and wild type (DTA-wt) group, and the relationship between gene mutation and clinical characteristics and prognosis was analyzed. RESULTS: Among the 102 MDS patients, 96% (98/102) presented with mutation, while the mean number of mutations was 3.04 mutations/patient. DTA-mut was detected in 56.9% (58/102) patients. The most frequent co-mutated genes in DTA-mut group were SF3B1 (25.8%), RUNX1 (24.1%), U2AF1 (18.9%), SRSF2, EZH2, SETBP1 (17.2%), STAG2 (15.5%), IDH2 (12.1%) and BCOR, CBL (10.3%). The two groups showed no significant differences in ages, blood parameters, bone marrow blasts, WHO 2022 classification, IPSS-R risk category and rate of conversion to leukemia. Compared with the DTA-wt group, the mutation frequency of RUNX1 was higher (P = 0.02), while mutation frequency of TP53 was lower (P = 0.001) and the mutation frequency of ≥ 3 co-mutated genes was higher in DTA-mut group (P = 0.00). Survival analysis showed that the overall survivals (OS) of DTA-mut patients was significantly inferior to that of DTA-wt patients (P = 0.0332). According to IPSS-R classification, a statistically significant difference in OS was only observed in higher risk (IPSS-R > 3.5) group (P = 0.0058). In the context of DTA mutation, the OS of patients with RUNX1 mutation was shorter than that of patients without RUNX1 mutation significantly (P = 0.0074). The OS of patients with SF3B1 mutation was longer than that of patients without SF3B1 mutation, but there was no statistical difference (P = 0.0827). DTA mutations were not independent prognostic factors when DTA and co-mutated genes with frequency > 10% were considered in Cox regression model (P = 0.329). However, multivariate analysis confirmed an independently adverse prognosis of RUNX1 co-mutation (P = 0.042, HR = 2.426, 95% CI:1.031-5.711) in DTA-mut cohort. Moreover, our multivariable analysis suggests that SRSF2-mut was an independent poor prognostic factor for all MDS patients (P = 0.047), but lost significance (P = 0.103) for DTA-mut patients. CONCLUSIONS: DTA mutations are frequently observed in patients with MDS, often accompanied by genes involved in RNA splicing and transcription factors like SF3B1 and RUNX1. DTA and concomitant mutations affect prognosis in MDS patients and RUNX1 was identified as an independent poor prognostic factor in patients with DTA mutations.

Female gametophyte development is required for nucellar-tip degeneration during Arabidopsis ovule development.

MAIN CONCLUSION: Genetic ablation of the female gametophyte provides direct evidence for the existence of interregional communication during Arabidopsis ovule development and the importance of the female gametophyte in nucellar-tip degeneration. The angiosperm ovule consists of three regions: the female gametophyte, the nucellus, and the integuments, all of which develop synchronously and coordinately. Previously, interregional communication enabling cooperative ovule development had been proposed; however, the evidence for these communications mostly relies on the analysis of mutant phenotypes. To provide direct evidence, we specifically ablated the Arabidopsis female gametophyte by expressing the diphtheria toxin fragment A (DTA) under the female gametophyte-specific DD13 promoter and analyzed its effects on the development of the nucellus and the integuments. We found that the female gametophyte is not required for integument development or for the orientation and curvature of the ovule body, but is necessary for nucellar-tip degeneration. The results presented here provide direct evidence for communication from the female gametophyte to the nucellus and demonstrate that Arabidopsis ovules require interregional communication for cooperative development.

Diagnostic performance of ultrasound elastography in differentiating hepatocellular carcinoma and intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

PURPOSE: To evaluate the diagnostic value of ultrasound elastography (USE) for characterizing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: The protocol was pre-registered a priori at ( https://osf.io/namvk/ ). Using PubMed, Web of Science, Embase, and Cochrane Library, we found studies up to April 20, 2024 by searching HCC, ICC, and USE as keywords. Parameters of USE were directly compared between HCC and ICC patients using random-effects bivariate model on STATA 17.0, MedCalc 20.0, and Psychometrica. Trim & fill method and sensitivity analysis were also performed. RESULTS: Eighteen studies were included with 1057 patients, consisting of 863 HCC lesions, 188 ICC lesions, and 6 mixed lesions. The pooled Emean values of HCC and ICC were 28.3 (CI = 19.8 to 36.8) and 44.0 (CI = 20.9 to 67.2). HCC tumors were 34.3% softer than ICC while peritumoral tissue in HCC lesions was 75% stiffer than ICC lesions based on Emean. The strain value index (tumoral-to-peritumoral ratio) in HCC patients was 49.4% less than that of ICC patients. USE demonstrated a pool sensitivity of 87% (CI = 73-95%), specificity of 82% (CI = 65-92%), positive likelihood ratio of 4.8 (CI = 2.2 to 10.3), negative likelihood ratio of 0.16 (CI = 0.07 to 0.37), and diagnostic odds ratio of 31 (CI = 7 to 127) in differentiation of ICC from HCC. CONCLUSION: By evaluating tumoral and pre-tumoral stiffness, along with strain value index, USE may provide a valuable quantitative diagnostic tool for accurately differentiating HCC and ICC.

[Prognostic Value of DTA Mutations in Patients with Newly Diagnosed Acute Myeloid Leukemia].

OBJECTIVE: To investigate the prognostic significance of DTA (DNMT3A, TET2, ASXL1 ) gene mutations in patients with non-M3 acute myeloid leukemia (AML). METHODS: The clinical data of 180 newly diagnosed AML patients hospitalized in the First People's Hospital of Changzhou from January 2018 to April 2022 were retrospectively analyzed. Next-generation sequencing technology was used to detect 150 gene mutations in the patients, and log-rank tests and Cox regression models were used to analyze the prognostic factors. RESULTS: DTA gene mutations were detected in 83 (46.1%) of 180 AML patients. Compared to patients without DTA mutations, patients with DTA mutations were significantly older (P < 0.001). The median overall survival (OS) time and disease-free survival (DFS) time in the DTA mutation group were significantly shorter than those in the group without DTA mutation (both P < 0.05). Multivariate analysis showed that age ≥ 60 years (P < 0.001), with DTA mutation (P =0.018), and intermediate-risk (relative to favorable-risk) (P =0.005) were independent risk factors for OS in AML patients. CONCLUSION: AML patients with DTA mutations are relatively older, with shorter median OS time and DFS time, and poor prognosis.

Low serum adrenic acid levels in infants and subsequent food-induced anaphylaxis.

Background: The dietary fat hypothesis links increases in allergic diseases to reduced consumption of n-3 polyunsaturated fatty acids from fish, for example, eicosapentaenoic acid, and increased intake of n-6 polyunsaturated fatty acids from vegetable oils, for example, arachidonic acid. Objective: Building upon the "fat hypothesis," we sought to investigate the association between 24 types of serum fatty acid levels in infants and the risk of subsequent food-induced anaphylaxis (FIA) by age 2 years as the primary outcome. Methods: This study was conducted as a prespecified supplemental analysis within the ABC randomized clinical trial. We measured levels of 24 fatty acids in residual serum samples collected from 268 infants at age 5 to 6 months using gas chromatography-mass spectrometry. Results: Among the 258 infants, 58 exhibited immediate-type food allergies, whereas 200 showed no food allergy. Of the 58 infants, 12 were diagnosed with FIA, whereas the remaining 46 had nonanaphylactic food allergy. Unexpectedly, among the 24 fatty acids, only adrenic acid, also known as docosatetraenoic acid, which is one of the n-6 polyunsaturated fatty acids, showed significantly lower levels in infants with FIA (median [interquartile range] (wt.%), 0.16 [0.14-0.17]), compared with those with no food allergy (0.19 [0.17-0.21]) (P = .0007). In contrast, adrenic acid levels in infants with nonanaphylactic food allergy were 0.19 [0.16-0.21] (wt.%), which did not differ significantly from those in infants with no food allergy (P = .69). Conclusions: This study generated a hypothesis suggesting that infants with low serum adrenic acid levels might be at greater risk of subsequent FIA. This unexpected result warrants further investigation.

Assessing the influence of autumnal temperature fluctuations on cold hardiness in different grapevine cultivars: variations across vine age and bud positions.

The dynamic fluctuations in autumn temperatures, particularly the marked diurnal variations and the subsequent precipitous drops are key and a pivotal role in viticulture, as they critically influence the acclimation process of grapevines to cold, thereby directly impacting their survival and productivity in cold-climate regions. In this comprehensive study, we investigated the cold hardiness of four grapevine cultivars: 'Itasca', 'Frontenac', 'La Crescent', and 'Marquette', focusing on how these cultivars and their individual buds (1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, and 9th) respond to fluctuating weather and low temperatures typical of autumn [-1.1°C (30°F) -9.4°C (15°F) and -17.8°C (0°F)]. Our results illuminated the striking variability in cold hardiness that was manifest not only among the different cultivars but also within individual buds on the same vine, underscoring the critical influence of bud position on a vine for cold hardiness. 'Frontenac' showed greater cold hardiness at critical temperatures at which 10%, and 50% of the dormant buds were lethally affected by cold (LT10 and LT50) compared to 'Itasca' and 'La Crescent', with 'Marquette' exhibiting intermediate values. However, in cultivars such as 'Itasca' and 'Marquette', certain buds demonstrated a pronounced hardiness when faced with colder temperatures, while others exhibited a heightened sensitivity, thereby revealing a nuanced interplay between bud position and a vine's ability to withstand cold stress. Our study revealed a notable divergence from traditional viticulture understanding; apical buds demonstrated greater cold hardiness than basal buds and opened new paths for research into grapevine physiology. Our results also indicated a significant trend wherein older vines across all studied cultivars displayed enhanced cold hardiness, particularly pronounced at the critical LT50 and the critical temperature at which 90% of the dormant buds were lethally affected by cold (LT90) thresholds, in comparison to younger vines. Moreover, our findings shed light on the impact of autumn's diurnal temperature variations and the subsequent drop in temperatures on vine cold hardiness, thus highlighted the complex interplay between environmental temperature dynamics and dormant bud hardiness. In conclusion, our study showed that the cold damage observed in grapevines in North Dakota was not a result of extreme temperature fluctuations in the fall. This was confirmed by testing the vines after they had reached various threshold temperatures through differential thermal analysis (DTA) and optical differential nucleation and expansion analysis (ODNEAL) methodologies, particularly before the onset of severe pre-winter cold conditions. These comprehensive findings highlighted the complexity of the vine's response to climatic conditions and viticultural management, pointing to the need for specific strategies in vineyard management and cultivar selection to optimize bud hardiness and productivity in the face of various environmental challenges, especially in cold climate viticulture.

Keratin 19 (Krt19) is a novel marker gene for epicardial cells.

Epicardial cells regulate heart growth by secreting numerous growth factors and undergoing lineage specification into other cardiac lineages. However, the lack of specific marker genes for epicardial cells has hindered the understanding of this cell type in heart development. Through the analysis of a cardiac single cell mRNA sequencing dataset, we identified a novel epicardial gene named Keratin 19 (Krt19). Further analysis of the expression patterns of Krt19 and Wt1, a well-known epicardial gene, revealed their preferences in major cardiac cell types. Using lineage-tracing analysis, we analyzed Krt19-CreER labeled cells at multiple time windows and found that it labels epicardial cells at both embryonic and neonatal stages. Furthermore, we studied the function of epicardial cells using a diphtheria toxin A chain (DTA)-based cell ablation system. We discovered that Krt19-CreER labeled cells are essential for fetal heart development. Finally, we investigated the function of Krt19-CreER and Wt1-CreER labeled cells in neonatal mouse development. We observed that the Krt19-CreER; Rosa-DTA mice displayed a smaller size after tamoxifen treatment, suggesting the potential importance of Krt19-CreER labeled cells in neonatal mouse development. Additionally, we found that Wt1-CreER; Rosa-DTA mice died at early stages, likely due to defects in the kidney and spleen. In summary, we have identified Krt19 as a new epicardial cell marker gene and further explored the function of epicardial cells using the Krt19-CreER and Wt1-CreER-mediated DTA ablation system.

[Relationship between DTA Mutations and Thromboembolism in Patients with Myeloproliferative Neoplasms].

OBJECTIVE: To analyze the DTA (DNMT3A, TET2, ASXL1) mutations in patients with myeloproliferative neoplasms (MPN), and preliminarily explore their correlation with thromboembolism. METHODS: Clinical characteristics of 62 patients diagnosed de novo MPN at Central Hospital Affiliated to Shandong First Medical University from September 2016 to September 2022 were retrospectively analyzed. Next-generation sequencing was used to detect 35 MPN-related genes, and the DTA mutations in MPN patients and their relationship with thromboembolic events were analyzed. RESULTS: 75.8% (47/62) of the patients presented pathogenic non-driver mutations, and the mean number of pathogenic non-driver mutations per patient was 1.08. Among them, the most frequently mutated non-driver genes were TET2 (38.7%, 24/62), DNMT3A (9.7%, 6/62) and ASXL1 (6.5%, 4/62). The presence of DTA gene mutations was 50% (31/62) in the total MPN patients, and mainly accompanied by driver mutations. The mutation rate of DTA in patients aged ≥60 years was significantly higher than that in patients <60 years old (P =0.039). The incidence of thromboembolism in patients with DTA mutation was 58.1% (18/31), which was significantly higher than that in patients without DTA mutation (19.4%, 6/31) (P =0.002). The TET2 gene mutation rate in MPN patients with thromboembolism was 66.7% (16/24), which was significantly higher than that in patients without thromboembolism (21.1%, 8/38) (P =0.00). CONCLUSION: Patients with MPN have a higher incidence of DTA mutations, which are mainly accompanied by driver gene mutations. The incidence of thromboembolism in MPN patients with DTA mutations is higher than that in patients without DTA mutations. Especially, the elderly (≥60 years) essential thrombocythemia(ET) and polycythemia vera(PV) patients with TET2 mutation should be vigilant for thromboembolic events.

Adaption and application of cell-based bioassays to whole-water samples.

The increasing presence of contaminants of emerging concern in wastewater and their potential environmental risks require improved monitoring and analysis methods. Direct toxicity assessment (DTA) using bioassays can complement chemical analysis of wastewater discharge, but traditional in vivo tests have ethical considerations and are expensive, low-throughput, and limited to apical endpoints (mortality, reproduction, development, and growth). In vitro bioassays offer an alternative approach that is cheaper, faster, and more ethical, and can provide higher sensitivity for some environmentally relevant endpoints. This study explores the potential benefits of using whole water samples of wastewater and environmental surface water instead of traditional solid phase extraction (SPE) methods for in vitro bioassays testing. Whole water samples produced a stronger response in most bioassays, likely due to the loss or alteration of contaminants during SPE sample extraction. In addition, there was no notable difference in results for most bioassays after freezing whole water samples, which allows for increased flexibility in testing timelines and cost savings. These findings highlight the potential advantages of using whole water samples in DTA and provide a framework for future research in this area.

Fabrication of nano filler doped PVA/starch biodegradable composites with enhanced thermal conduction, water barrier and antimicrobial performance for food industry.

In this work there was investigated the synergistic effect of the nanomaterials-the Montmorillonite (MMT) and the vanadium pentoxide (V2O5) on the polyvinyl alcohol (PVA)/starch composite. The composite films were prepared by the solvent casting method. The characterization of the composites showed that the addition of the MMT and the V2O5 to PVA/starch composite decreased the water solubility and water absorption capacity of the film. Both of the reinforcement materials enriched values of thermal conductivity and thermal stability of the composite. The TG/DTA and universal testing machine (UTM) analysis exhibited that MMT and V2O5 augmented the thermal robustness and tensile strength of composites and decreased the strain to break. It was also observed that greater MMT concentration accelerates mechanical strength deterioration of the film owing to agglomeration. The scanning electron microscopy (SEM) analysis reflected great change in the surface morphology of the films in the presence and absence of MMT and V2O5. This was due to the interaction amid constituents of the composite. The chemical interaction between the PVA, Starch, MMT and the V2O5 was also established via Fourier-transform infrared spectroscopy (FTIR) analysis, which revealed fluctuations in the absorbance position and intensity of the PVA/Starch. Antimicrobial activities against seven different cultures of bacteria (both-gram positive and -negative) and one fungus (Candida albicans), exposed that antimicrobial performance of the PVA amplified upon addition of the starch, MMT and V2O5, making these composites prospective candidates for the biodegradable packaging materials.

Characterization of lead sulfide obtained from Naga Bhasma.

BACKGROUND: Lead sulfide nanoparticles were manufactured from lead oxide using a procedure described in the Ayurveda formulary of India, which involved using a quantum of the heat of up to 60 puta, which is officially known as the Shasti puta Naga Bhasma. OBJECTIVE: The study shows sulfurization of nanoparticles decreased their toxicity due to the lower solubility. MATERIALS AND METHODS: The present work used the arsenic sulfide media and traditional puta for processing and the characterization of the same has been conducted. Different analytical techniques like X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-Ray (EDX) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and thermo-gravimetry analysis (TGA) were used. RESULTS: Powder x-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, Thermogravimetric analysis, and differential thermal analysis all showed that the produced nanoparticles are lead sulfide nanoparticles with a particle size of an average of 84.60 and the crystalline average size of 69.06 nm. CONCLUSION: The rounded, rod, oval, cubic, and circular morphology of the produced lead sulfide nanoparticles can be seen in the SEM image. The stretching and bending functional groups in the sample were alkanes, alkenes, aromatic hydrocarbons, carboxylic acids, alkyl carboxylic acids, alkyl alpha, beta-unsaturated, aldehydes, ketones, carboxylic acid, aliphatic amines, primary amines, secondary amines, alkyl halides, are studied through the FTIR spectrum.

Comparative Studies of the Structural and Physicochemical Properties of the First Fullerene Derivative FD-C60 (Fullerenol) and Second Fullerene Derivate SD-C60 (3HFWC).

In order to maximally reduce the toxicity of fullerenol (the first derivative of C60, FD-C60), and increase its biomedical efficiency, the second derivative SD-C60 (3HFWC, Hyper-Harmonized Hydroxylated Fullerene Water Complex) was created. Several different methods were applied in the comparative characterization of FD-C60 and SD-C60 with the same OH groups in their core. FD-C60 as an individual structure was about 1.3 nm in size, while SD-C60 as an individual structure was 10-30 nm in size. Based on ten physicochemical methods and techniques, FD-C60 and SD-C60 were found to be two different substances in terms of size, structure, and physicochemical properties; FD-C60, at 100 °C, had endothermic characteristics, while SD-C60, at 133 °C, had exothermic characteristics; FD-C60 did not have water layers, while SD-C60 had water layers; the zeta potential of FD-C60 was -25.85 mV, while it was -43.29 mV for SD-C60. SD-C60 is a promising substance for use in cosmetics and pharmaceuticals.

5-ALA, DTA-6, and Nitrogen Mitigate NaCl Stress by Promoting Photosynthesis and Carbon Metabolism in Rice Seedlings.

A large number of dead seedlings can occur in saline soils, which seriously affects the large-scale cultivation of rice. This study investigated the effects of plant growth regulators (PGRs) and nitrogen application on seedling growth and salt tolerance (Oryza sativa L.), which is of great significance for agricultural production practices. A conventional rice variety, "Huang Huazhan", was selected for this study. Non-salt stress treatments included 0% NaCl (CK treatment), CK + 0.05 g N/pot (N treatment), CK + 40 mg·L-1 5-aminolevulinic acid (5-ALA) (A treatment), and CK + 30 mg·L-1 diethylaminoethyl acetate (DTA-6) (D treatment). Salt stress treatments included 0.3% NaCl (S treatment), N + 0.3% NaCl (NS treatment), A + 0.3% NaCl (AS treatment), and D + 0.3% NaCl (DS treatment). When 3 leaves and 1 heart emerged from the soil, plants were sprayed with DTA-6 and 5-ALA, followed by the application of 0.3% NaCl (w/w) to the soil after 24 h. Seedling morphology and photosynthetic indices, as well as carbohydrate metabolism and key enzyme activities, were determined for each treatment. Our results showed that N, A, and D treatments promoted seedling growth, photosynthesis, carbohydrate levels, and the activities of key enzymes involved in carbon metabolism when compared to the CK treatment. The A treatment had the most significant effect, with increases in aboveground dry weight and net photosynthetic rates (Pn) ranging from 17.74% to 41.02% and 3.61% to 32.60%, respectively. Stomatal limiting values (Ls) significantly decreased from 19.17% to 43.02%. Salt stress significantly inhibited seedling growth. NS, AS, and DS treatments alleviated the morphological and physiological damage of salt stress on seedlings when compared to the S treatment. The AS treatment was the most effective in improving seedling morphology, promoting photosynthesis, increasing carbohydrate levels, and key enzyme activities. After AS treatment, increases in aboveground dry weight, net photosynthetic rate, soluble sugar content, total sucrose synthase, and amylase activities were 17.50% to 50.79%, 11.39% to 98.10%, 20.20% to 80.85%, 21.21% to 33.53%, and 22.17% to 34.19%, respectively, when compared to the S treatment. In summary, foliar sprays of 5-ALA, DTA-6, and additional nitrogen fertilizer enhanced rice seedling growth, increased photosynthesis, lowered Ls values, and improved seedling salt tolerance. Spraying two regulators, 5-ALA and DTA-6, quantitatively increased the effect of nitrogen fertilizer, with comparable effects on NaCl stress regulation. This study provides the basis for efficient agricultural production.

Thermogravimetric/Thermal-Mass Spectroscopy Insight into Oxidation Propensity of Various Mechanochemically Made Kesterite Cu2ZnSnS4 Nanopowders.

Thermogravimetry coupled with thermal analysis and quadrupole mass spectroscopy TGA/DTA-QMS were primarily used to assess the oxidation susceptibility of a pool of nanocrystalline powders of the semiconductor kesterite Cu2ZnSnS4 for prospective photovoltaic applications, which were prepared via the mechanochemically assisted synthesis route from two different precursor systems. Each system, as confirmed by XRD patterns, yielded first the cubic polytype of kesterite with defunct semiconductor properties, which, after thermal annealing at 500 °C under neutral gas atmosphere, was converted to the tetragonal semiconductor polytype. The TGA/DTA-QMS determinations up to 1000 °C were carried out under a neutral argon Ar atmosphere and under a dry, oxygen-containing gas mixture of O2:Ar = 1:4 (vol.). The mass spectroscopy data confirmed that under each of the gas atmospheres, a distinctly different, multistep evolution of such oxygen-bearing gaseous compounds as sulfur oxides SO2/SO3, carbon dioxide CO2, and water vapor H2O was taking place. The TGA/DTA changes in correlation with the nature of evolving gases helped in the elucidation of the plausible chemistry linked to kesterite oxidation, both in the stage of nanopowder synthesis/storage at ambient air conditions and during forced oxidation up to 1000 °C in the dry, oxygen-containing gas mixture.

Plant growth regulators mitigate oxidative damage to rice seedling roots by NaCl stress.

The aim of this experiment was to investigate the effects of exogenous sprays of 5-aminolevulinic acid (5-ALA) and 2-Diethylaminoethyl hexanoate (DTA-6) on the growth and salt tolerance of rice (Oryza sativa L.) seedlings. This study was conducted in a solar greenhouse at Guangdong Ocean University, where 'Huanghuazhan' was selected as the test material, and 40 mg/L 5-ALA and 30 mg/L DTA-6 were applied as foliar sprays at the three-leaf-one-heart stage of rice, followed by treatment with 0.3% NaCl (W/W) 24 h later. A total of six treatments were set up as follows: (1) CK: control, (2) A: 40 mg⋅ L-1 5-ALA, (3) D: 30 mg⋅ L-1 DTA-6, (4) S: 0.3% NaCl, (5) AS: 40 mg⋅ L-1 5-ALA + 0.3% NaCl, and (6) DS: 30 mg⋅ L-1 DTA-6+0.3% NaCl. Samples were taken at 1, 4, 7, 10, and 13 d after NaCl treatment to determine the morphology and physiological and biochemical indices of rice roots. The results showed that NaCl stress significantly inhibited rice growth; disrupted the antioxidant system; increased the rates of malondialdehyde, hydrogen peroxide, and superoxide anion production; and affected the content of related hormones. Malondialdehyde content, hydrogen peroxide content, and superoxide anion production rate significantly increased from 12.57% to 21.82%, 18.12% to 63.10%, and 7.17% to 56.20%, respectively, in the S treatment group compared to the CK group. Under salt stress, foliar sprays of both 5-ALA and DTA-6 increased antioxidant enzyme activities and osmoregulatory substance content; expanded non-enzymatic antioxidant AsA and GSH content; reduced reactive oxygen species (ROS) accumulation; lowered malondialdehyde content; increased endogenous hormones GA3, JA, IAA, SA, and ZR content; and lowered ABA content in the rice root system. The MDA, H2O2, and O2- contents were reduced from 35.64% to 56.92%, 22.30% to 53.47%, and 7.06% to 20.01%, respectively, in the AS treatment group compared with the S treatment group. In the DS treatment group, the MDA, H2O2, and O2- contents were reduced from 24.60% to 51.09%, 12.14% to 59.05%, and 12.70% to 45.20%. In summary, NaCl stress exerted an inhibitory effect on the rice root system, both foliar sprays of 5-ALA and DTA-6 alleviated damage from NaCl stress on the rice root system, and the effect of 5-ALA was better than that of DTA-6.

G-K BertDTA: A graph representation learning and semantic embedding-based framework for drug-target affinity prediction.

Developing new drugs is costly, time-consuming, and risky. Drug-target affinity (DTA), indicating the binding capability between drugs and target proteins, is a crucial indicator for drug development. Accurately predicting interaction strength between new drug-target pairs by analyzing previous experiments aids in screening potential drug molecules, repurposing them, and developing safe and effective medicines. Existing computational models for DTA prediction rely on strings or single-graph neural networks, lacking consideration of protein structure and molecular semantic information, leading to limited accuracy. Our experiments demonstrate that string-based methods may overlook protein conformations, causing a high root mean square error (RMSE) of 3.584 in affinity due to a lack of spatial context. Single graph networks also underperform on topology features, with a 6% lower confidence interval (CI) for activity classification. Absent semantic information also limits generalization across diverse compounds, resulting in 18% increment in RMSE and 5% in misclassifications within quantifications study, restricting potential drug discovery. To address these limitations, we propose G-K BertDTA, a novel framework for accurate DTA prediction incorporating protein features, molecular semantic features, and molecular structural information. In this proposed model, we represent drugs as graphs, with a GIN employed to learn the molecular topological information. For the extraction of protein structural features, we utilize a DenseNet architecture. A knowledge-based BERT semantic model is incorporated to obtain rich pre-trained semantic embeddings, thereby enhancing the feature information. We extensively evaluated our proposed approach on the publicly available benchmark datasets (i.e., KIBA and Davis), and experimental results demonstrate the promising performance of our method, which consistently outperforms previous state-of-the-art approaches. Code is available at https://github.com/AmbitYuki/G-K-BertDTA.

LSTM-SAGDTA: Predicting Drug-target Binding Affinity with an Attention Graph Neural Network and LSTM Approach.

INTRODUCTION: Drug development is a challenging and costly process, yet it plays a crucial role in improving healthcare outcomes. Drug development requires extensive research and testing to meet the demands for economic efficiency, cures, and pain relief. METHODS: Drug development is a vital research area that necessitates innovation and collaboration to achieve significant breakthroughs. Computer-aided drug design provides a promising avenue for drug discovery and development by reducing costs and improving the efficiency of drug design and testing. RESULTS: In this study, a novel model, namely LSTM-SAGDTA, capable of accurately predicting drug-target binding affinity, was developed. We employed SeqVec for characterizing the protein and utilized the graph neural networks to capture information on drug molecules. By introducing self-attentive graph pooling, the model achieved greater accuracy and efficiency in predicting drug-target binding affinity. CONCLUSION: Moreover, LSTM-SAGDTA obtained superior accuracy over current state-of-the-art methods only by using less training time. The results of experiments suggest that this method represents a highprecision solution for the DTA predictor.

Time-driven activity-based costing (TDABC) of direct-to-angiography pathway for acute ischemic stroke patients with suspected large vessel occlusion.

INTRODUCTION: Direct-to-angiography (DTA) is a novel care pathway for endovascular treatment (EVT) of acute ischemic stroke (AIS) that has been shown to reduce time-to-treatment and improve clinical outcomes for EVT-eligible patients. The institutional costs of adopting the DTA pathway and the many factors affecting costs have not been studied. In this study, we assess the costs and main cost drivers associated with the DTA pathway compared to the conventional CT pathway for patients presenting with AIS and suspected LVO in the anterior circulation. METHODS: Time driven activity based costing (TDABC) model was used to compare costs of DTA and conventional pathways from the healthcare institution perspective. Process mapping was used to outline all activities and resources (personnel, equipment, materials) needed for each step in both pathways. The cost model was developed using our institutional patient database and average New York state wages for personnel costs. Total, incremental and proportional costs were calculated based on institutional and patient factors affecting the pathways. RESULTS: DTA pathway accrued additional $82,583.61 (9%) in total costs compared to the conventional approach for all AIS patients. For EVT-ineligible patients, the DTA pathway incurred additional $82,964.37 (76%) in total costs compared to the CT pathway. For EVT eligible patients, the total and per-patient costs were greater in the CT pathway by $380.76 (0.04%) and $5.60 (0.04%) respectively. CONCLUSION: As the DTA pathway incurred additional $82,964.37 for EVT-ineligible patients, appropriate patient selection criteria are needed to avoid transferring EVT-ineligible patients to the angiography suite.

Characterization of sago tree parts from Sentani, Papua, Indonesia for biomass energy utilization.

Biomass derived from organic waste in industrial processes is an effective method to mitigate the negative impacts of agricultural waste materials. In Sentani, Papua, one such potential biomass source is sago tree waste. This study characterized the waste from the bark, middle, and inner parts of the sago tree to evaluate its biomass energy potential. Scanning electron microscopy with energy-dispersive X-ray (SEM-EDX) analysis of the complete sample revealed that oxygen, carbon, and silicon were the primary elements, with carbon content ranging from 30.75 % to 38.87 %. This indicates that all parts of the sago plant have the potential to be used as biomass fuel. Thermogravimetric analysis (TGA) results showed that the inner section of the sago had the lowest moisture content at approximately 13.3 %, followed by the outer part at 42 % and the bark at 55 %. The inner section had the highest lignin content, approximately 37 %, and exhibited the slowest thermal degradation in the differential thermal analysis (DTA) profile. The outer and bark parts of the sago were more reactive in stage II of the DTA profile, suggesting a higher concentration of cellulose and hemicellulose compared to lignin, making them suitable for gasification and pyrolysis. The heating value of sago bark was determined to be 12.85 MJ/kg (adb). These findings underscore the potential of sago waste as a renewable energy source, particularly in remote areas.