Search Results (5,054)

PROTACs, proteolysis targeting chimeras, are bifunctional molecules inducing protein degradation through a unique proximity-based mode of action. While offering several advantages unachievable by classical drugs, PROTACs have unfavorable physicochemical properties that pose challenges in application and formulation. In this study, we show the solubility enhancement of two PROTACs, ARV-110 and SelDeg51, using Poly(vinyl alcohol). Hereby, we apply a three-fluid nozzle spray drying set-up to generate an amorphous solid dispersion with a 30% w/w drug loading with the respective PROTACs and the hydrophilic polymer. Dissolution enhancement was achieved and demonstrated for t = 0 and t = 4 weeks at 5 °C using a phosphate buffer with a pH of 6.8. A pH shift study on ARV-110-PVA is shown, covering transfer from simulated gastric fluid (SGF) at pH 2.0 to fasted-state simulated intestinal fluid (FaSSIF) at pH 6.5. Additionally, activity studies and binding assays of the pure SelDeg51 versus the spray-dried SelDeg51-PVA indicate no difference between both samples. Our results show how modern enabling formulation technologies can partially alleviate challenging physicochemical properties, such as the poor solubility of increasingly large ‘small’ molecules. Full article

Efficient water supply and timely detection of drought stress in crops to increase yields is an important task considering that agriculture is the primary consumer of water globally. This is particularly significant for plants such as sunflowers, which are an important source of quality edible oils, essential for human nutrition. Traditional detection methods are labor-intensive, time-consuming, and rely on advanced sensor technologies. We introduce an innovative approach based on neural networks and transfer learning for drought stress detection using a novel dataset including 209 non-invasive rhizotron images and 385 images of manually cleaned sections of sunflowers, subjected to normal watering or water stress. We used five neural network models: VGG16, VGG19, InceptionV3, DenseNet, and MobileNet, pre-trained on the ImageNet dataset, whose performance was compared to select the most efficient architecture. Accordingly, the most efficient model, MobileNet, was further refined using different data augmentation mechanisms. The introduction of targeted data augmentation and the use of grayscale images proved to be effective, demonstrating improved results, with an F1 score and an accuracy of 0.95. This approach encourages advances in water stress detection, highlighting the value of artificial intelligence in improving crop health monitoring and management for more resilient agricultural practices. Full article

High-definition near-eye display technology has extremely close sight distance, placing a higher demand on the size, performance, and array of light-emitting pixel devices. Based on the excellent photoelectric performance of metal halide perovskite materials, perovskite light-emitting diodes (PeLEDs) have high photoelectric conversion efficiency, adjustable emission spectra, and excellent charge transfer characteristics, demonstrating great prospects as next-generation light sources. Despite their potential, the solubility of perovskite in photoresist presents a hurdle for conventional micro/nano processing techniques, resulting in device sizes typically exceeding 50 μm. This limitation impedes the further downsizing of perovskite-based components. Herein, we propose a plane-structured PeLED device that can achieve microscale light-emitting diodes with a single pixel device size < 2 μm and a luminescence lifetime of approximately 3 s. This is accomplished by fabricating a patterned substrate and regulating ion distribution in the perovskite through self-doping effects to form a PN junction. This breakthrough overcomes the technical challenge of perovskite–photoresist incompatibility, which has hindered the development of perovskite materials in micro/nano optoelectronic devices. The strides made in this study open up promising avenues for the advancement of PeLEDs within the realm of micro/nano optoelectronic devices. Full article

In this paper, referring to Kaya’s method, the ratio of gross agricultural production (GAP) and agricultural carbon emission is defined as agricultural carbon emission efficiency (ACEE). Considering rural labor transfer (RLT) increases the agricultural machinery intensity (AMI), the two are substitutes for each other and may interact with agricultural carbon emission efficiency (ACEE). We constructed a Simultaneous Equations Model (SEM) of ACEE, RLT and AMI and analyzed the interaction mechanism of these three variables using the Three-Stage Least Squares (3SLS). The following conclusions are drawn. First, RLT and AMI significantly promote the improvement of ACEE, while the improvement of ACEE and AMI further promotes RLT. Secondly, the causal relationship and influence mechanism of ACEE, RLT and AMI are interactive and multi-directional. For example, an increase in AMI promotes ACEE, but an increase in ACEE inhibits an increase in AMI. Finally, China has significant regional heterogeneity, and different regions have different interaction mechanisms. Local governments should consider the local economic base and technological level when implementing policies. This paper extends the analytical framework of ACEE, RLT, and AMI and provides a reference for governments to make policies. Full article

In response to the current lack of annotations for flower images and insufficient focus on key image features in traditional fine-grained flower image classification based on deep learning, this study proposes the SA-ConvNeXt flower image classification model. Initially, in the image preprocessing stage, a padding algorithm was used to prevent image deformation and loss of detail caused by scaling. Subsequently, the model was integrated using multi-level feature extraction within the Efficient Channel Attention (ECA) mechanism, forming an M-ECA structure to capture channel features at different levels; a pixel attention mechanism was also introduced to filter out irrelevant or noisy information in the images. Following this, a parameter-free attention module (SimAM) was introduced after deep convolution in the ConvNeXt Block to reweight the input features. SANet, which combines M-ECA and pixel attention mechanisms, was employed at the end of the module to further enhance the model’s dynamic extraction capability of channel and pixel features. Considering the model’s generalization capability, transfer learning was utilized to migrate the pretrained weights of ConvNeXt on the ImageNet dataset to the SA-ConvNeXt model. During training, the Focal Loss function and the Adam optimizer were used to address sample imbalance and reduce gradient fluctuations, thereby enhancing training stability. Finally, the Grad-CAM++ technique was used to generate heatmaps of classification predictions, facilitating the visualization of effective features and deepening the understanding of the model’s focus areas. Comparative experiments were conducted on the Oxford Flowers102 flower image dataset. Compared to existing flower image classification technologies, SA-ConvNeXt performed excellently, achieving a high accuracy of 96.7% and a recall rate of 98.2%, with improvements of 4.0% and 3.7%, respectively, compared to the original ConvNeXt. The results demonstrate that SA-ConvNeXt can effectively capture more accurate key features of flower images, providing an effective technical means for flower recognition and classification. Full article

To facilitate the utility of field effect transistor (FET)-type sensors, achieving sensitivity enhancement beyond the Nernst limit is crucial. Thus, this study proposed a novel approach for the development of ferroelectric FETs (FeFETs) using lead zirconate titanate (PZT) ferroelectric films integrated with indium–tungsten oxide (IWO) channels synthesized via a cost-effective sol-gel process. The electrical properties of PZT-IWO FeFET devices were significantly enhanced through the strategic implementation of PZT film treatment by employing intentional annealing procedures. Consequently, key performance metrics, including the transfer curve on/off ratio and subthreshold swings, were improved. Moreover, unprecedented electrical stability was realized by eliminating the hysteresis effect during double sweeps. By leveraging a single-gate configuration as an FeFET transformation element, extended-gate (EG) detection methodologies for pH sensing were explored, thereby introducing a pioneering dimension to sensor architecture. A measurement paradigm inspired by plane gate work was adopted, and the proposed device exhibited significant resistive coupling, consequently surpassing the sensitivity thresholds of conventional ion-sensitive field-effect transistors. This achievement represents a substantial paradigm shift in the landscape of ion-sensing methodologies, surpassing the established Nernst limit (59.14 mV/pH). Furthermore, this study advances FeFET technology and paves the way for the realization of highly sensitive and reliable ion sensing modalities. Full article

National pricing and reimbursement agencies face growing challenges with complex health technologies, prompting European policy advancements. Beneluxa is a cross-country collaboration involving Belgium, the Netherlands, Luxemburg, Austria, and Ireland that aims to address sustainable access to medicines. In view of the soon-to-be-implemented EU HTA Regulation, insights and experiences from stakeholders with Beneluxa cross-country collaboration could provide possible transferable learnings. Therefore, this research aims to (i) identify the opportunities and challenges faced by Beneluxa, (ii) gather insights from stakeholders, namely (possible) applicants and policymakers, within and beyond Beneluxa on the initiative and broader cross-country collaboration principles, and (iii) transfer these insights into learnings and recommendations in anticipation of the full implementation of the new HTA Regulation. Fifteen semi-structured interviews were conducted with industry and European HTA/policy stakeholders. The principal challenges discussed by stakeholders encompass hesitancy from the industry toward Beneluxa assessments, which were attributed to procedural and timeline uncertainties, legislative framework ambiguity, and challenges in terms of industry’s internal organization. Another challenge highlighted is the resource-intensive nature of the procedure due to diverse approaches among member states. In addition, industry stakeholders mentioned limited communication and procedural complexity. Despite challenges, both stakeholder groups recognized important opportunities for cross-country collaboration. Transferable insights for future cross-country collaboration include transparent communication, clear legislative embedding, internal industry restructuring to facilitate joint HTAs, and member state support for conducting collaborative assessments. The study underscores diverging views among stakeholders on cross-country collaboration’s potential to support HTA and the market access of complex health technologies. While acknowledging benefits, there still are challenges, including industry hesitancy, emphasizing the need for transparent communication and clear guidance in the evolving EU HTA landscape. Full article

The assessment of human liver stem cells (HLSCs) as cell therapeutics requires scalable, controlled expansion processes. We first focused on defining appropriate process parameters for HLSC expansion such as seeding density, use of antibiotics, optimal cell age and critical metabolite concentrations in conventional 2D culture systems. For scale-up, we transferred HLSC expansion to multi-plate and stirred-tank bioreactor systems to determine their limitations. A seeding density of 4000 cells cm⁻² was needed for efficient expansion. Although growth was not significantly affected by antibiotics, the concentrations of lactate and ammonia were important. A maximum expansion capacity of at least 20 cumulative population doublings (cPDs) was observed, confirming HLSC growth, identity and functionality. For the expansion of HLSCs in the multi-plate bioreactor system Xpansion (XPN), the oxygen supply strategy was optimized due to a low k_La of 0.076 h⁻¹. The XPN bioreactor yielded a final mean cell density of 94 ± 8 × 10³ cells cm⁻², more than double that of the standard process in T-flasks. However, in the larger XPN50 device, HLSC density reached only 28 ± 0.9 × 10³ cells cm⁻², while the glucose consumption rate increased 8-fold. In a fully-controlled 2 L stirred-tank bioreactor (STR), HLSCs expanded at a comparable rate to the T-flask and XPN50 processes in a homogeneous microenvironment using advanced process analytical technology. Ultimately, the scale-up of HLSCs was successful using two different bioreactor systems, resulting in sufficient numbers of viable, functional and undifferentiated HLSCs for therapeutic applications. Full article

Organic pollutants were one of the main sources of environmental pollutants. The degradation of organic pollutants through photocatalytic technology was one of the effective solutions. By preparing zinc oxide(ZnO) nanowires modified with sodium-doped conjugated 2,4,6-triaminopyrimidin-g-C₃N₄ (NaTCN) heterojunction (ZnO/NaTCN), the photocatalytic performance of NaTCN modified with different ratios of ZnO was systematically studied. The photocatalytic performance was studied through the degradation performance of methyl blue (MB) dye. The results showed that 22.5 wt% ZnO/NaTCN had the best degradation effect on MB dye. The degradation rate of MB reached 98.54% in 70 min. After three cycles, it shows good cycling stability (degradation rate is 96.99%) for dye degradation. It was found that there are two types of active species: ·OH and h⁺, of which h⁺ is the main active species produced by photocatalytic degradation of dyes. The excellent degradation performance was attributed to the fact that ZnO facilitated the extraction and transport of photogenerated carriers. The doping of sodium facilitated charge transfer. The NaTCN conjugated system promoted the extraction and transfer of photogenerated carriers. It provided guidance for designing efficient composite catalysts for use in other renewable energy fields. Full article

The export of trimmed coconuts necessitates controlling microbial growth and browning, often achieved through the use of sodium metabisulfite (SMS). However, SMS can elicit allergic reactions in operators. To address this concern, ultrafine bubble (UFBs) technology was applied to reduce the SMS concentration. Trimmed coconuts were dipped in either a 1.5% SMS solution or a combination of 1.5% SMS with UFBs (1.5% SMS-UFBs) and compared to coconuts dipped or not dipped in a 3% SMS solution. All treated coconuts were then wrapped with polyvinyl chloride (PVC) film and stored at 2–4 °C for 2 months, followed by transfer to storage at 8–10 °C for an additional 14 days. The results indicated that halving the SMS concentration, with or without UFB application, effectively controlled microbial growth and browning, comparable to using 3% SMS. No contamination of E. coli or Salmonella spp. was detected. The mesocarp whiteness, browning index, polyphenol oxidase (PPO) activity, and total phenolic content of coconuts treated with 1.5% SMS or 1.5% SMS-UFBs did not differ significantly from those dipped in 3% SMS solution (p > 0.05). Similarly, the quality of coconut water and coconut meat in SMS or SMS-UFB treatments did not show significant differences. In dry seasons, using 1.5% SMS with or without UFBs yielded comparable results to those obtained using 3% SMS. However, in wet seasons, the synergistic effects of UFBs on reducing microbial growth incidence were observed, similar to the impact achieved with 3% SMS, whereas 1.5% SMS alone did not inhibit microbial growth. Overall, UFB technology shows promise in reducing SMS concentration by 50% for trimmed young coconuts throughout the year. Full article

Plant flowering time is affected by endogenous and exogenous factors, but its variation patterns among different populations of a species has not been fully established. In this study, 27 Arabidopsis thaliana accessions were used to investigate the relationship between autonomous pathway gene methylation, gene expression and flowering time variation. DNA methylation analysis, RT-qPCR and transgenic verification showed that variation in the flowering time among the Arabidopsis populations ranged from 19 to 55 days and was significantly correlated with methylation of the coding regions of six upstream genes in the autonomous pathway, FLOWERING LOCUS VE (FVE), FLOWERING LOCUS Y (FY), FLOWERING LOCUS D (FLD), PEPPER (PEP), HISTONE DEACETYLASE 5 (HAD5) and Pre-mRNA Processing Protein 39-1 (PRP39-1), as well as their relative expression levels. The expression of FVE and FVE(CS) was modified separately through degenerate codon substitution of cytosine and led to earlier flowering of transgenic plants by 8 days and 25 days, respectively. An accurate determination of methylated sites in FVE and FVE(CS) among those transgenic plants and the recipient Col-0 verified the close relationship between the number of methylation sites, expression and flowering time. Our findings suggest that the methylation variation of these six key upstream transcription factors was associated with the gene expression level of the autonomous pathway and flowering time in Arabidopsis. The FVE(CS) and FVE genes in transgenic plants tended to be hypermethylated, which could be a protective mechanism for plants. However, modification of gene sequences through degenerate codon substitution to reduce cytosine can avoid hypermethylated transferred genes in transgenic plants. It may be possible to partially regulate the flowering of plants by modified trans-epigenetic technology. Full article

Heat exchangers make it possible to utilize energy efficiently, reducing the cost of energy production or consumption. For example, they can be used to improve the efficiency of gas turbines. Improving the efficiency of a heat exchanger directly affects the efficiency of the device for which it is used. One of the most effective ways to intensify heat exchange in a heat exchanger without a significant increase in mass-dimensional characteristics and changes in the input parameters of the flows is the introduction of turbulators into the heat exchangers. This article investigates the increase in efficiency of heat exchanger apparatuses by introducing turbulent lattice structures manufactured with the use of additive technologies into their design. The study is carried out by numerical modeling of the heat transfer process for two sections of the heat exchanger: with and without the lattice structure inside. It was found that lattice structures intensify the heat exchange by creating vortex flow structures, as well as by increasing the heat exchange area. Thus, the ratio of convection in thermal conductivity increases to 3.03 times. Also in the article, a comparative analysis of the results obtained with the results of heat transfer intensification using classical flow turbulators is carried out. According to the results of the analysis, it was determined that the investigated turbulators are more effective than classical ones, however, the pressure losses in the investigated turbulators are much higher. Full article

This paper address the performance optimization of the battery heat sink module by analyzing the lattice structure of the battery heat sink module through in-depth modeling and simulation, and combining the laser powder bed fusion (LPBF)-forming technology with mechanical and corrosion resistance experiments for a comprehensive study. It is found that the introduction of the lattice skeleton significantly improves the thermal conductivity of the phase change material (PCM), realizing the efficient distribution and fast transfer of heat in the system. At the same time, the lattice skeleton makes the heat distribution in the heat exchanger more uniform, improves the utilization rate of the PCM, and helps to maintain the stability of the cell temperature. In addition, the melting of PCM in the lattice heat exchanger is more uniform, thus maximizing its latent heat capacity. In summary, by optimizing the lattice structure and introducing the lattice skeleton, this study successfully improves the performance of the battery heat dissipation system, which provides a strong guarantee for the high efficiency and stable operation of the battery, and provides new ideas and references for the development of the battery heat dissipation technology. Full article

Solid crystalline suspensions (SCSs) containing submicron particles were introduced as a competitive solution to increase dissolution rates and the bioavailability of poorly water-soluble drugs. In an SCS, poorly water-soluble drug crystals are finely dispersed in a hydrophilic matrix. Lately, melt milling as an adapted wet milling process at elevated temperatures has been introduced as a suitable batch manufacturing process for such a formulation. In this work, the transfer from batch operation to a two-step continuous process is demonstrated to highlight the potential of this technology as an alternative to other dissolution-enhancing methods. In the first step, a powder mixture of a model drug (griseofulvin) and a carrier (xylitol) is fed to an extruder, where a uniform suspension is obtained. In the second step, the suspension is transferred to a custom-built annular gap mill, where comminution down to the submicron region takes place. The prototype’s design was based on batch grinding results and a narrow residence time distribution, intended to deliver large quantities of submicron particles in the SCS. The throughput of the mill was found to be limited by grinding media compression. By inclining the mill at an angle, the grinding media position was manipulated, such that compression was avoided. Different states of the grinding media in the grinding chamber were identified under surrogate conditions. This strategy allows the maintenance of an energy-optimized comminution without adaption of the associated process parameters, even at high throughputs. Using this new process, the production of an SCS with 80–90 % submicron particles in a single passthrough was demonstrated. Full article

This paper describes a study on the heat transfer properties of the deeply buried pipeline energy pile group, which is an efficient and convenient geothermal development technology. Through in situ experiments and a simulation algorithm, the research investigated the heat transmission characteristics of the deeply buried pipe energy pile group and optimized different intermittent operation schemes. The findings suggest that prolonged operation of the pile cluster intensifies heat buildup within the pile foundation, thereby adversely affecting the system’s overall heat exchange efficiency. Employing an intermittent operating mode can alleviate this heat accumulation phenomenon, thereby promoting sustained heat exchange performance of the piles over time. To evaluate the comprehensive thermal interaction and energy efficiency ratio of the energy pile heat exchange system, various intermittent operation strategies were compared in the study. Among them, the intermittent operational scheme with a ratio of n = 5 was found to be optimal, with the total average heat transfer rate of the pile set only 0.51% lower than that of the continuous operational mode, but the overall energy efficiency ratio improved by 19.6%. The intermittent operational mode proposed in this study can achieve the goal of saving energy and efficiently extracting geothermal resources, providing theoretical guidance for the extraction and utilization of subsurface geothermal power by energy piles. Full article