Single-point mutations in the Kirsten rat sarcoma (KRAS) viral proto-oncogene are the most common cause of human cancer. In humans, oncogenic KRAS mutations are responsible for about 30% of lung, pancreatic, and colon cancers. One of the predominant mutant KRAS G12D variants is responsible for pancreatic cancer and is an attractive drug target. At the time of writing, no Food and Drug Administration (FDA) approved drugs are available for the KRAS G12D mutant. So, there is a need to develop an effective drug for KRAS G12D. The process of finding new drugs is expensive and time-consuming. On the other hand, in silico drug designing methodologies are cost-effective and less time-consuming. Herein, we employed machine learning algorithms such as K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF) for the identification of new inhibitors against the KRAS G12D mutant. A total of 82 hits were predicted as active against the KRAS G12D mutant. The active hits were docked into the active site of the KRAS G12D mutant. Furthermore, to evaluate the stability of the compounds with a good docking score, the top two complexes and the standard complex (MRTX-1133) were subjected to 200 ns MD simulation. The top two hits revealed high stability as compared to the standard compound. The binding energy of the top two hits was good as compared to the standard compound. Our identified hits have the potential to inhibit the KRAS G12D mutation and can help combat cancer. To the best of our knowledge, this is the first study in which machine-learning-based virtual screening, molecular docking, and molecular dynamics simulation were carried out for the identification of new promising inhibitors for the KRAS G12D mutant. Full article

A novel second-generation blue fluorescent polyamidoamine dendrimer peripherally modified with sixteen 4-N,N-dimethylaninoethyloxy-1,8-naphthalimide units was synthesized. Its basic photophysical characteristics were investigated in organic solvents of different polarity. It was found that in these solvents, the dendrimer is colorless and emitted blue fluorescence with different intensities depending on their polarity. The effect of the pH of the medium on the fluorescence intensity was investigated and it was found that in the acidic medium, the fluorescence is intense and is quenched in the alkaline medium. The ability of the dendrimer to detect metal ions (Pb²⁺, Zn²⁺, Mg²⁺, Sn²⁺, Ba²⁺, Ni²⁺, Sn²⁺, Mn²⁺, Co²⁺, Fe³⁺, and Al³⁺) was also investigated, and it was found that in the presence of Fe³⁺, the fluorescent intensity was amplified more than 66 times. The antimicrobial activity of the new compound has been tested in vitro against Gram-positive B. cereus and Gram-negative P. aeruginosa. The tests were performed in the dark and after irradiation with visible light. The antimicrobial activity of the compound enhanced after light irradiation and B. cereus was found slightly more sensitive than P. aeruginosa. The increase in antimicrobial activity after light irradiation is due to the generation of singlet oxygen particles, which attack bacterial cell membranes. Full article

The aim behind principal component pursuit is to recover a low-rank matrix and a sparse matrix from a noisy signal which is the sum of both matrices. This optimization problem is a priori and non-convex and is useful in signal processing, data compression, image processing, machine learning, fluid dynamics, and more. Here, a distributed scheme described by a static undirected graph, where each agent only observes part of the noisy or corrupted matrix, is applied to achieve a consensus; then, a robust approach that can also handle missing values is applied using alternating directions to solve the convex relaxation problem, which actually solves the non-convex problem under some weak assumptions. Some examples of image recovery are shown, where the network of agents achieves consensus exponentially fast. Full article

Background: We evaluate the relationship between corneal nerve structure and function in a veteran population. Methods: 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in this study. Each individual filled out questionnaires to evaluate ocular symptoms (5-Item Dry Eye Questionnaire, DEQ5; Ocular Surface Disease Index, OSDI) and ocular pain (Numerical Rating Scale, NRS; Neuropathic Pain Symptom Inventory modified for the Eye, NPSI-Eye). The individuals also underwent an ocular surface examination that captured functional nerve tests including corneal sensation, corneal staining, and the Schirmer test for tear production. Corneal sub-basal nerve analysis was conducted using in vivo confocal microscopy (IVCM) images with corneal nerve density, length, area, width, and fractal dimension captured. IVCM and functional corneal metrics from the right eye were examined using correlational and linear regression analysis. Results: Most corneal structural metrics were not related to functional metrics, except for weak correlations between various IVCM metrics and tear production. In addition, corneal nerve fiber area was positively related to corneal sensation (r = 0.3, p = 0.01). On linear regression analyses, only the corneal fractal dimension remained significantly related to tear production (β = −0.26, p = 0.02) and only the corneal nerve fiber area remained significantly related to corneal sensation (β = 0.3, p = 0.01). Conclusions: Most corneal nerve structural metrics did not relate to functional metrics in our veteran population, apart from a few weak correlations between structural metrics and tear production. This suggests that using corneal nerve anatomy alone may be insufficient for predicting corneal function. Full article

The Alpha navigation system is the only operating radio system based on very-low-frequency (VLF) signals that can be used to research VLF navigation, timing, and ionospheric characteristics. The detection of the Alpha navigation signal is the key step in the Alpha receiver; however, the received Alpha navigation signal is susceptible to noise and mutual interference, which deteriorates signal detection performance. This paper presents a multichannel orthogonal correlation method for Alpha navigation signal detection. Once the three frequency signals of the Alpha navigation system are obtained using a notch filter, station identification is realized using a multichannel orthogonal correlation method and signal format. The selection of key parameters and the detection performance under noise and mutual interference are analyzed. This method’s detection probability exceeds 90% when the signal-to-noise ratio (SNR) is greater than −10 dB. The influence of mutual interference on the signal correlation peak is less than 1% when the signal-to-interference ratio (SIR) of the mutual interference is greater than −28 dB. The proposed method is verified using an actual signal collected using an Alpha receiver. The results show that an Alpha signal can be detected at an extremely low SNR. This method has strong practicability and satisfies the application requirements of an Alpha receiver. Full article

The Rutaceae family is one of the most studied plant families due to the large number of alkaloids isolated from them with outstanding biological properties, among them the quinoline-based alkaloids Graveoline 1 and Dubamine 2. The most common methods for the synthesis of alkaloids 1 and 2 and their derivatives involves cycloaddition reactions or metal-catalyzed coupling processes but with some limitations in scope and functionalization of the quinoline moiety. As a continuation of our current studies on the synthesis and chemical transformation of 2-aminochalcones, we are reporting here an efficient metal-free approach for the total synthesis of alkaloids 1 and 2 along with their analogues with structural diversity, through a two-step sequence involving intramolecular cyclization, oxidation/aromatization, N-methylation and oxidative C-C bond processes, starting from dihydroquinolin-4-ones as common precursors for the construction of the structures of both classes of alkaloids. Full article

Trachoma is the world-leading infectious cause of preventable blindness and is caused by the bacteria Chlamydia trachomatis. In developing countries, diagnosis is usually based on clinical evaluation. Serological-based tests are cheaper than molecular-based ones, but the latter are more sensitive and specific. The present study developed a new duplex qPCR which concomitantly detects the C. trachomatis cryptic plasmid and the human 18S rRNA gene, with an LOD95% for C. trachomatis DNA of 13.04 genome equivalents per reaction. The new qPCR was tested using 50 samples from an endemic area and 12 from a non-endemic area that were previously characterized using direct immunofluorescence assay (DFA) and clinical evaluation. Among the 50 endemic samples, 3 were found to be positive by clinical evaluation (6%), 18 were found to be positive by DFA (36%), and 48 were found to be positive by qPCR (96%). Next, the new duplex qPCR was validated using 50 samples previously characterized by qPCR. Validation was carried out on a benchtop instrument (ABI7500) or on a portable point-of-care instrument (Q3-Plus), showing 95% specificity and 100% sensitivity. The ubiquitous presence of C. trachomatis DNA in samples from the endemic region confirms that constant monitoring is of paramount importance for the effective measurement of the elimination of trachoma. The newly developed duplex qPCR presented in this study, along with its validation in a portable qPCR system, constitutes important tools toward achieving this goal. Full article

With the rising prominence of organic farming systems in European Union countries, motivated by agricultural policies, there is pressure for effective disease management strategies. To address this challenge, the use of plant resistance inducers (PRIs) and elicitors has emerged as a promising approach. In this study, we compared the impact of integrated production with organic agriculture farming practices, specifically applying PRIs and elicitors in the latter, on the expression levels of stress-responsive genes in two grapevine cultivars, ‘Alicante Bouschet’ and ‘Trincadeira’. Our findings revealed that the organic farming system led to upregulation of eight of the 12 studied genes in at least one cultivar, indicating a significant influence of production mode. The upregulated genes were associated with plant stress-responsive genes (PR1, PR2, PR4, and TLP9), sugar metabolism (HT5), phenylpropanoids (STS1), enzymes related to jasmonic acid synthesis and response to biotic stresses, respectively (LOX, PER42). Also, the ‘Alicante Bouschet’ cultivar consistently displayed significantly higher levels of transcript accumulation on most of the stress-related genes compared to the ‘Trincadeira’ cultivar in both production modes. Our study provides valuable insights into the effectiveness of PRIs and elicitors in increasing plant expression levels of stress-responsive genes, leading to greater resilience to pathogen attacks and emphasizing their position in organic agriculture. Full article

Steam pretreatment at high temperatures enables fresh bamboo to possess antifungal and antiseptic properties. The process produces a large amount of wastewater that urgently needs to be recycled. Soluble bio-tars derived from wastewater under low-temperature (LTS-tar) and high-temperature (HTS-tar) steam pretreatments of moso bamboo were studied with a thermogravimetric analyzer coupled with Fourier transform infrared spectroscopy (TG–FTIR) and pyrolysis–gas-chromatography/mass spectrometry (Py–GC/MS). Thermogravimetric analysis showed that in the three stages of the thermal decomposition process, the final residue of the bamboo and HTS-tar had two main peaks of 0.88 wt% and 6.85 wt%. The LTS-tar had much more complicated thermal decomposition behavior, with six steps and a high residue yield of 23.86 wt%. A large quantity of CH₄ was observed at the maximum mass loss rates of the bamboo and bio-tars. Acids, aldehydes, ketones, esters, and phenolic compounds were found in the pyrolysis products of the bamboo and soluble bio-tars. Both bio-tars contained carbohydrates and lignin fragments, but the LTS-tar under mild steam conditions had more saccharides and was much more sensitive to temperature. The lignin in the bamboo degraded under harsh steam conditions, resulting in high aromatic and polymeric features for the HTS-tar. The significant differences between LTS-tar and HTS-tar require different techniques to achieve the resource utilization of wastewater in the bamboo industry. Full article

In the last decades, the development of PET/CT radiopharmaceuticals, targeting the Prostate-Specific Membrane Antigen (PSMA), changed the management of prostate cancer (PCa) patients thanks to its higher diagnostic accuracy in comparison with conventional imaging both in staging and in recurrence. Alongside molecular imaging, PSMA was studied as a therapeutic agent targeted with various isotopes. In 2021, results from the VISION trial led to the Food and Drug Administration (FDA) approval of [¹⁷⁷Lu]Lu-PSMA-617 as a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) and set the basis for a radical change in the future perspectives of PCa treatment and the history of Nuclear Medicine. Despite these promising results, primary resistance in patients treated with single-agent [¹⁷⁷Lu]Lu-PSMA-617 remains a real issue. Emerging trials are investigating the use of [¹⁷⁷Lu]Lu-PSMA-617 in combination with other PCa therapies in order to cover the multiple oncologic resistance pathways and to overcome tumor heterogeneity. In this review, our aim is to retrace the history of PSMA-targeted therapy from the first preclinical studies to its future applications in PCa. Full article

Nanoscale agrochemicals have been widely used in sustainable agriculture and may potentially affect the nitrogen fixation process in legume crops. The present study investigated the size-effects of copper oxide nanoparticles (CuO NPs) on nitrogen assimilation in soybean (G. max (L.) Merrill) plants, which were treated with different sizes (20 and 50 nm) of CuO NPs at low use doses (1 and 10 mg/kg) for 21 days under greenhouse conditions. The results showed that 50 nm CuO NPs significantly increased the fresh biomass more than 20 nm CuO NPs achieved at 10 mg/kg. The activities of N assimilation-associated enzymes and the contents of nitrogenous compounds, including nitrates, proteins, and amino acids, in soybean tissues were greatly increased across all the CuO NP treatments. The use doses of two sizes of CuO NPs had no impact on the Cu contents in shoots and roots but indeed increased the Cu contents in soils in a dose-dependent fashion. Overall, our findings demonstrated that both 20 and 50 nm CuO NPs could positively alter soybean growth and boost N assimilation, furthering our understanding that the application of nanoscale micro-nutrient-related agrochemicals at an optimal size and dose will greatly contribute to increasing the yield and quality of crops. Full article

The corrosion of steel materials has become a global issue, causing significant socio-economic losses and safety concerns. Hot-dip galvanizing is currently one of the most widely used steel anti-corrosion processes. With the rapid advancement of science and technology and emerging industries, the performance of pure galvanized products struggles to meet the demands of practical applications in various environments. Consequently, researchers have begun introducing various metals into the zinc solution to form high-performance alloy coatings. This article primarily explains the process flow of hot-dip galvanizing and the impact of metal elements such as Al, Mg, Sn, and Bi on the coating, as well as outlining the major issues currently faced by the hot-dip galvanizing process. The objective is to offer a more comprehensive introduction to those new to the field of hot-dip galvanizing and to provide theoretical insights for addressing production issues. Full article

Arsenic and antimony are impurities that reduce the economic value of concentrates due to the environmental problems they cause. The removal of these impurities by hydrometallurgical means has been highly studied for sulfide copper concentrates using different leaching agents in an alkaline medium (NaClO, H₂O₂, NaOH, Na₂S, NaHS, and S). For a lead–silver concentrate consisting of galena, sphalerite, and pyrite, it was possible to selectively reduce the arsenic content from 1.10% to 0.55% and antimony from 2.41 to 1.04% through the digestion-leaching technique that uses elemental sulfur as a leaching agent in alkaline medium. The adequate powdered sulfur and sodium hydroxide dosage were 336 and 342 kg/t, respectively. The process was carried out at 120 °C with a liquid/solid ratio of 2 in digestion and 5.67 in leaching; the appropriate digestion and leaching time were 20 and 30 min, respectively. The thermodynamics and kinetics of this process turned out to be very complex due to the great variety of simultaneous leaching and precipitation reactions. The digestion process exhibited a mixed kinetic control, where diffusion through the boundary layer and the chemical reaction were the controlling steps with an activation energy of 11.05 kcal/mol. Full article

This article focuses the event-triggered adaptive finite-time control scheme for the states constrained fractional-order nonlinear systems (FONSs) under uncertain parameters and external disturbances. The backstepping scheme is employed to construct the finite-time controller via a series of barrier Lyapunov function (BLF) to solve that all the state constraints are not violated. Different from the trigger condition with fixed value, the event-triggered strategy is applied to overcome the communication burden of controller caused by the limited communication resources. By utilizing fractional-order Lyapunov analysis, all variables in the resulted system are proven to be bounded, and the tracking error converges to the small neighborhood around origin in finite time and without the Zeno behavior. Finally, the effectiveness of the proposed control scheme is verified by the simulation analysis of a bus power system. Full article

Caregivers experience lower back pain due to patient transfer. Foot position is an important and adjustable posture for reducing lumbar loads during patient transfer. Specifically, a suitable foot position provides the use of the lower limbs instead of the lumbar region in patient handling. Thus, we have developed a monitoring and feedback system for foot positioning using wearable sensors to instruct suitable foot positions. However, existing measurement methods require multiple specific wearable sensors. In addition, the existing method has not been evaluated in patient transfer, including twisting and lowering. Thus, the objective of this study was to develop and evaluate a measurement method using only a smartphone-installed inertial sensor for foot position during patient transfer, including twisting and lowering. The smartphone attached to the trunk measures the acceleration, angular velocity, and geomagnetic field. The proposed method recognizes anteroposterior and mediolateral foot positions by machine learning using inertial data. The proposed method was tested using simulated patient transfer motions, including horizontal rotation. The results showed that the proposed method could recognize the two foot positions with more than 90% accuracy. These results indicate that the proposed method can be applied to wearable monitoring and feedback systems to prevent lower back pain caused by patient transfer. Full article

Cannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment. The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated the biological benefits and mechanism of hemp extract on CIPN. In the present study, hemp extract (JG) rich in cannabinoids was extracted by supercritical fluid carbon dioxide extraction (SFCE). The antinociceptive efficacy was evaluated using a paclitaxel-induced peripheral neuropathy (PIPN) rat model based on behavioral tests. Further omics-based approaches were applied to explore the potential mechanisms. The results showed that JG decreased mechanical allodynia, thermal hyperalgesia, and inflammatory cytokines in PIPN rats significantly. Transcriptome analysis identified seven key genes significantly regulated by JG in PIPN model rats, mainly related to the neuroactive ligand–receptor interaction pathway, PPAR signaling pathway, and cAMP signaling pathway. In metabolomic analysis, a total of 39 significantly altered metabolites were identified, mainly correlated with pentose and glucuronate interconversions and the glycerophospholipid metabolism pathway. Gut microbiota analysis suggested that increased community Lachnoclostridium and Lachnospiraceae_UCG-006 in PIPN rats can be reversed significantly by JG. In conclusion, hemp extract exhibited antinociceptive effects on PIPN. The analgesic mechanism was probably related to the regulation of inflammation, neuroactive ligand–receptor interaction pathway, sphingolipid metabolism, etc. This study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN. Full article

This study employs a multidisciplinary methodology across natural and social sciences to examine relationships between biodiversity loss at sea and urban consumption with a focus on sea cucumber and dried seafood markets in New York City (NYC). The study identified 34 dried seafood retailers across three NYC Chinatown boroughs: Manhattan, Brooklyn, and Queens. Samples of sea cucumber were collected with Chinese-language labels indicating the commodity was from South America, a region of conservation concern. Comparison samples were taken from sea cucumbers labeled from Mexico and Japan. A mitochondrial DNA barcoding method was used to examine the taxonomic origin of 103 samples. Sequence data were successfully obtained from 74 of the samples, 8 of which were classified as brown sea cucumber (Isostichopus fuscus), an endangered species for which harvest is banned in several locations. Semi-structured interviews with dried seafood retailers and consumers (n = 64), moreover, revealed associations between consuming sea cucumber and enhancing human health and limited knowledge of product origins. Collectively, the findings reveal socio-ecological dynamics wherein endangered species on the market coupled with geographic market labeling practices and varying degrees of retailer and consumer knowledge negatively bear on marine biodiversity. Furthermore, given that brown sea cucumbers are abundant on the market, there is a need for developing genetic markers that can trace geographic origin to determine if species were legally harvested. These results indicate that more robust market labeling, training, genetic research, and public outreach are required to advance One Health in urban seafood markets. Full article

Additive manufacturing (AM) is an advanced manufacturing method that produces objects by sequential layering. Material extrusion AM (MEAM) with continuous-fibre reinforcement is becoming more widely used in naval structures, which are exposed to the marine environment. However, the water diffusion process and the effect of water ageing on the mechanical performance of AM materials are not yet well understood because of their complex internal structure, caused by defects generated during manufacturing. Current research on diffusion is mostly based on experimental methods for conventionally manufactured materials without considering AM-induced defects. The objective of this study is to explore how the defects inherent to MEAM affect water diffusion in a composite material by the capillary effect. Results from a numerical study of capillary flow in MEAM polymer are applied as a boundary condition in the subsequent finite-element analysis. The study illustrates that flow in the capillary reaches the steady state quicker compared to the saturation time in the matrix, predicted by Fick’s diffusion equation. It is demonstrated that the capillary effect can significantly affect the water diffusion in MEAM parts and reduce the saturation time to one-third compared to the case without accounting for this effect. Full article

The figure of the child is one that, at least in the Westernised imagination, is entangled with notions of innocence, naivety, and freedom. But what of the child who is unfree, who has been stripped of innocence, and for whom naivety is a danger? One expression of this iteration of the figure of the child is the child soldier, which has been a centralising figure in various narratives set during and concerned with African experiences of warfare. This paper is concerned with the figure of the child soldier as it is staged in both Edward Zwick’s Blood Diamond (2006) and Cary Joji Fukunaga’s filmic adaptation of Uzodinma Iweala’s novel, Beasts of No Nation (2015). In turning to Ashis Nandy’s articulation of the tension held within “the child” as being both emblematic of a fantasy of childhood produced by adult nostalgia—hopeful, joyous and free—and always potentially dangerous, this paper pivots the notions of soldiering and slaving on and around the child as a figure. In doing so, the paper asks what it might mean to think of the condition of being a child soldier as being akin to that of being a child slave, weaponised for political and economic ends. Full article

Impaired neuronal plasticity and cognitive decline are cardinal features of Alzheimer’s disease and related Tauopathies. Aberrantly modified Tau protein and neurotransmitter imbalance, predominantly involving acetylcholine, have been linked to these symptoms. In Drosophila, we have shown that dTau loss specifically enhances associative long-term olfactory memory, impairs foot shock habituation, and deregulates proteins involved in the regulation of neurotransmitter levels, particularly acetylcholine. Interestingly, upon choline treatment, the habituation and memory performance of mutants are restored to that of control flies. Based on these surprising results, we decided to use our well-established genetic model to understand how habituation deficits and memory performance correlate with different aspects of choline physiology as an essential component of the neurotransmitter acetylcholine, the lipid phosphatidylcholine, and the osmoregulator betaine. The results revealed that the two observed phenotypes are reversed by different choline metabolites, implying that they are governed by different underlying mechanisms. This work can contribute to a broader knowledge about the physiologic function of Tau, which may be translated into understanding the mechanisms of Tauopathies. Full article

Success in integrating artificial intelligence (AI) in anesthesia depends on collaboration with anesthesiologists, respecting their expertise, and understanding their opinions. The aim of this study was to illustrate the confidence in AI integration in perioperative anesthetic care among Jordanian anesthesiologists and anesthesia residents working at tertiary teaching hospitals. This cross-sectional study was conducted via self-administered online questionnaire and includes 118 responses from 44 anesthesiologists and 74 anesthesia residents. We used a five-point Likert scale to investigate the confidence in AI’s role in different aspects of the perioperative period. A significant difference was found between anesthesiologists and anesthesia residents in confidence in the role of AI in operating room logistics and management, with an average score of 3.6 ± 1.3 among residents compared to 2.9 ± 1.4 among specialists (p = 0.012). The role of AI in event prediction under anesthesia scored 3.5 ± 1.4 among residents compared to 2.9 ± 1.4 among specialists (p = 0.032) and the role of AI in decision-making in anesthetic complications 3.3 ± 1.4 among residents and 2.8 ± 1.4 among specialists (p = 0.034). Also, 65 (55.1%) were concerned that the integration of AI will lead to less human–human interaction, while 81 (68.6%) believed that AI-based technology will lead to more adherence to guidelines. In conclusion, AI has the potential to be a revolutionary tool in anesthesia, and hesitancy towards increased dependency on this technology is decreasing with newer generations of practitioners. Full article