Biomimetic stimuli-responsive materials can respond to various external stimuli in the form of structural or morphological transformations by actively or passively converting input energy into mechanical energy. They are the core element of soft actuators for typical smart devices like soft robots, artificial muscles, intelligent sensors and nanogenerators. While significant progresses have been made in bioinspired stimuli-responsive materials, they have not yet achieved the remarkable properties in biological systems. In this review, we will discuss recent advances in biomimetic stimuli-responsive materials that are instrumental for soft actuators. Different stimuli-responsive principles for soft actuators are firstly discussed, including fluidic, electrical, thermal, magnetic, light and chemical stimuli. We further summarize the state-of-the-art stimuli-responsive materials for soft actuators and explore the advantages and disadvantages of using electroactive polymers, magnetic soft composites, hydrogels, liquid crystal elastomers, shape memory alloys and chemical-responsive materials. Finally, we provide a critical outlook on the field of stimuli-responsive soft actuators, and emphasize the challenges in the process of their implementation to various industries.

Herein, we report a stimuli responsive hydrogel with inhibitory activity against Escherichia coli prepared by chemical crosslinking of carboxymethyl chitosan (CMCs) and hydroxyethyl cellulose (HEC). The hydrogels were prepared by esterification of chitosan (Cs) with monochloroacetic acid to produce CMCs which was then chemically crosslinked to HEC using citric acid as the crosslinking agent. To impart a stimuli responsiveness property to the hydrogels, polydiacetylene-zinc oxide (PDA-ZnO) nanosheets were synthesized in-situ during the crosslinking reaction followed by photopolymerization of the resultant composite. To achieve this, ZnO was anchored on carboxylic groups in 10,12-pentacosadiynoic acid (PCDA) layers to restrict movement of alkyl portion of PCDA during crosslinking CMCs and HEC hydrogels. This was followed by irradiating the composite with UV radiation to photopolymerize the PCDA to PDA within the hydrogel matrix so as to impart thermal and pH responsiveness to the hydrogel. From the results obtained, the prepared hydrogel had a pH dependant swelling capacity as it absorbed more water in acidic media as compared to basic media. Incorporation of PDA-ZnO resulted in a thermochromic composite responsive to pH evidenced by a visible colour transition from pale purple to pale pink. Upon swelling, PDA-ZnO-CMCs-HEC hydrogels had inhibitory activity against E. coli attributed to the slow release of the ZnO nanoparticles as compared to CMCs-HEC hydrogels.

Hybrid microparticles based on an iron core and amphiphilic shell have been prepared to respond simultaneously to external (magnetic and ultrasounds field) and internal (pH) stimuli for delivery of the anticancer drug doxorubicin. The microparticles have been prepared in three main steps; including surface modification of the iron core followed by conjugation with the amphiphilic chitosan and drug loading. The particles demonstrate spherical shape and dimension in the range 1-3 m with tunable surface charge by changing the pH of surrounding environment. The microparticles demonstrate good stability in simulated physiological solutions and able to allocate up to 400 g of drug per mg of bare carrier. The response to ultrasound and the changes in the shell structure when exposed to different pH allows to control the doxorubicin release. In vitro cytotoxicity tests performed on fibloblast NIH/3T3 demonstrate a reduction in the cell viability when doxorubicin was administrated by microparticles compared to the free formulation; in particular when ultrasound were applied. The bare microparticles demonstrate cytocompatibility and hemocompatibility up to 50g/mL and 60 g/mL, respectively.

Smart materials represent an elegant class of (macro)-molecules endowed with the ability to react to chemical/physical changes in the environment. Herein, we prepared new photo responsive azobenzenes possessing halogen bond donor groups. The X-ray structures of two molecules highlight supramolecular organizations governed by unusual noncovalent bonds. In azo dye I-azo-NO2, the nitro group is engaged in orthogonal H···O···I halogen and hydrogen bonding, linking the units in parallel undulating chains. As far as compound I-azo-NH-MMA is concerned, a non-centrosymmetric pattern is formed due to a very rare I···π interaction involving the alkene group supplemented by hydrogen bonds. The Cambridge Structural Database contains only four structures showing the same I···CH₂=C contact. For all compounds, an ¹⁹F NMR spectroscopic analysis confirms the formation of halogen bonds in solution through a recognition process with chloride anion, and the reversible photo-responsiveness is demonstrated upon exposing a solution to UV light irradiation. Finally, the intermediate I-azo-NH2 also shows a pronounced color change due to pH variation. These azobenzenes are thereby attractive building blocks to design future multi-stimuli responsive materials for highly functional devices.

As the use of microbial inoculants in agriculture rises, it becomes important to understand how the environment may influence microbial ability to promote plant growth. This work examines whether there are light dependencies in the biological functions of Azospirillum brasilense, a commercialized prolific grass-root colonizer. Though classically defined as non-phototrophic, A. brasilense possesses photoreceptors that could perceive light conducted through its host’s roots. Evidence for light dependency of four microbial processes were examined and noted: biological nitrogen fixation (BNF), auxin biosynthesis, ATP biosynthesis, and iron and manganese uptake. Functional mutants of A. brasilense were leveraged and studied in light and dark environments: HM053 (high BNF and auxin production), ipdC (capable of BNF, deficient in auxin production), and FP10 (capable of auxin production, deficient in BNF). HM053 exhibited the highest rate of nitrogenase activity with the greatest light dependency comparing iterations in light and dark environments. The ipdC mutant showed similar behavior with relatively lower nitrogenase activity observed, while FP10 did not show a light dependency. Auxin biosynthesis showed strong light dependencies in HM053 and FP10 strains, but not for ipdC. Iron is involved in the BNF biological process, and light dependency was observed for microbial 59Fe2+ uptake in HM053 and ipdC, but not FP10. Surprisingly, a light dependency for 52Mn2+ uptake was only observed in ipdC. Finally, ATP biosynthesis was sensitive to light across all three mutants favoring blue light over red light compared to darkness with observed ATP levels in descending order for HM053 > ipdC > FP10.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

This study aimed to evaluate the effects of Blazepod technology when incorporated with various training regimens on the essential elements of physical fitness in volleyball, such as agility, speed, visual response time, and vertical leap. Thirty-six participants (age :17.33±0.48 y, height: 183.78±6.34 cm, weight: 77.14±5.16 kg) were in-volved in this study. In randomized design, three equal groups with two experimental groups and one control group were involved in the study over a period of six weeks: (GE1) used Blazepod technology to workout at a low level; (GE2) used Blazepod technology to workout at a higher intensity; (CG) did not employ Blazepod technology, but it adhered to the same fundamental training curriculum. We conducted agility, speed, reaction time, and vertical jump tests before, midway and after the study to determine optimal training volume, intensity, and frequency. A significant main effect of time (P0.01), and time×group interaction (P>0.001) were found for all tests. Post hoc test showed that the two experimental groups gadget significantly improved in all performance variables (P

Salt stress is a major limiting factor for alfalfa yield due to its relatively low salt tolerance. High soil salinity adversely impacts alfalfa growth and development, leading to reduced yield. Melatonin (MT) is known to play a significant role in enhancing plant resistance to abiotic stresses. However, the mechanisms underlying melatonin-mediated abiotic stress responses, particularly salt stress, are not well understood. To address this gap, we conducted a study focusing on germinating alfalfa seeds under salt stress. Physiological indexes and transcriptomics analyses were carried out on the germinated seeds to investigate the effects of melatonin on alfalfa seedlings under salt stress conditions. Our results revealed that the application of melatonin led to an increase in shoot length and fresh weight of alfalfa seedlings under salt stress. Moreover, key physiological indexes such as peroxidase (POD) activity and glutathione (GSH) content were enhanced, while levels of malondialdehyde and superoxide anions decreased. Transcriptomic analysis identified a total of 2,131 differentially expressed genes in the salt-treated group, with 726 up-regulated and 1,405 down-regulated genes, while the MT-treated group showed 2896 differentially expressed genes, of which 1,097 were up-regulated and 1,799 were down-regulated. Further, KEGG enrichment analysis highlighted the enrichment of differentially expressed genes in pathways including flavonoid biosynthesis, ABC transporter, glutathione metabolism, and the MAPK signaling pathway, with these pathways more significantly enriched in the MT-treated group. These findings collectively suggest that melatonin plays a crucial role in alfalfa's response to salt stress and offer new insights into the genomic mechanisms underlying melatonin-mediated salt tolerance in alfalfa.

Salt stress is one of the major abiotic stresses that lead to crop yield reduction worldwide. Melatonin (MT), an endogenous hormone synthesized in plants, plays an important role in responding to abiotic stimuli such as drought, salinity, heat, cold, etc. However, the molecular mechanisms of MT-mediated abiotic stresses remain to be better understood. In order to explore the key genes and pathways of melatonin in alleviating salt stress, physiological and biochemical indicators as well as transcriptomics profile were conducted in alfalfa seedlings. The results showed that the germination rate, bud length and fresh weight of alfalfa seedlings added with melatonin were higher than those treated with salt alone. In addition, Malondialdehyde (MDA) and Superoxide anion (O2-) contents also displayed a decreasing trend. The activity and content of Superoxide dismutase (SOD)、peroxidase (POD) and Glutathione (GSH) increased to varying degrees. In order to further reveal the molecular mechanism of MT-mediated salt tolerance of alfalfa, transcriptome analysis was performed on alfalfa seedlings. 2,181 differentially expressed genes (DEGs) were obtained in the salt-treated group, including 780 upregulated genes and 1,401 down-regulated genes, while 4,422 DEGs were obtained in the MT group, among which 1,438 were upregulated and 2,984 were downregulated. By using GO functional annotation and KEGG pathway enrichment, we found that DEGs were mainly enriched in the biosynthesis of flavonoids, isoflavones, plant hormones, Glutathione (GSH), soluble sugars and other substances, as well as in the ABC transporter and MAPK signaling pathways. Among them, the DEGs in the MT group was more enriched in these pathways, suggesting that MT can combat salt stress by regulating the expression of genes related to phytohormone and antioxidant capacity, which has important reference value for the breeding of salt-tolerant alfalfa and other crops.

Phenylketonuria is an inherited metabolic disorder that leads to neurobehavioral dysfunction. The main treatment is a low-phenylalanine diet and/or the cofactor tetrahydrobiopterin. Regular outpatient follow-up care and measurement of the phenylalanine level in the blood are required. We aimed to analyze the economic burden of phenylketonuria on families and the state. The pa-tients with phenylketonuria were divided into three groups according to their treatment: a low-phenylalanine diet group (n= 50), a tetrahydrobiopterin group (n= 44) and a group taking tetra-hydrobiopterin together with the diet (n= 25). A comparative cost analysis was carried out. The annual economic burden to the state was calculated to average €18801±15345 and was lowest in the diet group, then in the tetrahydrobiopterin group and highest in the tetrahydrobiopterin+diet group (p < 0.001). Out-of-pocket costs amounted to €1531±1173 per year, and indirect losses aver-aged €2125±1930 per year for all families. The economic loss was significantly lower in the fami-lies taking tetrahydrobiopterin than in the other groups (p=0.001). The combined use of medical nutrition and BH4 treatments has been shown to increase the economic harm to the state. Reim-bursing low-protein products and increasing the rate of patients eligible for financial allowances may reduce the economic harm to families.

Sentence stimuli pervade psycholinguistics research. Yet limited attention has been paid to the automatic construction of sentence stimuli. Given their linguistic capabilities, this study investigated the efficacy of ChatGPT/AI tools in generating sentence stimuli. In three psycholinguistic experiments, this study examined the acceptability and validity of AI-formulated auditory sentences and written sentences in two languages: English and Arabic. Participants gave English AI-generated stimuli similar to or higher acceptability ratings than human-composed stimuli, but the opposite was observed for Arabic AI-generated stimuli. The validity of AI-developed stimuli relied on the study design, with only Experiment 2 demonstrating the target psycholinguistic effect (L1/L2 morphosyntactic prediction). These results highlight the promising role of AI as a stimuli developer which could facilitate psycholinguistic research and increase its diversity. Implications for psycholinguistic research were discussed.

Both auditory and vestibular primary afferent neurons can be activated by sound and vibration. This review relates differences between them to the different receptor/synaptic mechanisms of the two systems as shown by indicators of peripheral function – cochlear and vestibular compound action potentials (cCAPs and vCAPs) to click stimulation as recorded in animal studies. Sound and vibration sensitive type 1 receptors at the striola of the utricular macula are enveloped by the unique calyx afferent ending which has three modes of synaptic transmission. Glutamate is the transmitter for both cochlear and vestibular primary afferents, however blocking glutamate transmission has very little effect on vCAPs but greatly reduces cCAPs. We suggest that the ultrafast non-quantal synaptic mechanism called resistive coupling is the cause of the short latency vestibular afferent responses and related results – failure of transmitter blockade, masking, and temporal precision. This “ultrafast” non-quantal transmission is effectively electrical coupling dependent on the membrane potentials of the calyx and the type 1 receptor. The major clinical implication is that decreasing stimulus rise-time increases vCAP response, corresponding to the increased VEMP response in human subjects . Short rise-times are optimum in human clinical VEMP testing, whereas long rise-times are mandatory for audiometric threshold testing.

The aim of this study was to examine brightness effect, which is the perceptual property of visual stimuli, on brain responses obtained during visual processing of these stimuli. For this purpose, brain responses of the brain to changes in brightness were explored comparatively using different emotional images (pleasant, unpleasant and neutral) with different luminance levels. Moreover, electroencephalography recordings from 12 different electrode sites of 31 healthy participants were used. The power spectra obtained from the analysis of the recordings using short time Fourier transform were analyzed, and a statistical analysis was performed on features extracted from these power spectra. Statistical findings obtained from electrophysiological data were compared with those obtained from behavioral data. The results showed that the brightness of visual stimuli affected the power of brain responses depending on frequency, time and location. According to the statistically verified findings, the distinctive effect of brightness occurred in the parietal and occipital regions for all the three types of stimuli. Accordingly, the increase in the brightness of pleasant and neutral images increased the average power of responses in the parietal and occipital regions whereas the increase in the brightness of unpleasant images decreased the average power of responses in these regions. However, the increase in brightness for all the three types of stimuli reduced the average power of frontal and central region responses (except for 100-300 ms time window for unpleasant stimuli). The statistical results obtained for unpleasant images were found to be in accordance with the behavioral data. The results also revealed that the brightness of visual stimuli could be represented by changing the activity power of the brain cortex. The main contribution of this research was to comprehensively examine brightness effect on brain activity for images with different emotional content and different frequency bands at different time windows of visual processing for different brain regions. The findings emphasized that the brightness of visual stimuli should be viewed as an important parameter in studies using emotional image techniques such as image classification, emotion evaluation and neuro-marketing.

Sweetness drives consumption of added sugars, so understanding how individuals differ is important for developing strategies to lower sugar intake. However, methods to assess hedonic response to sweetness vary, making results across studies difficult to integrate. We compared methods to measure optimal sucrose concentration in 21 healthy adults (1) using paired-comparison preference tracking vs. ratings of liking, (2) with participants in the laboratory vs. at home, and (3) using aqueous solutions vs. vanilla milk. Tests were replicated on separate days to assess test-retest reliability. Test-retest reliability was similar between laboratory and home testing, but tended to be better for vanilla milk and preference tracking. Optimal sucrose concentration was virtually identical between laboratory and home, slightly lower when estimated via preference tracking, and about 50% lower in vanilla milk. However, individual optimal sucrose concentration correlated strongly between Methods, test Locations, and Stimuli. More than 50% of the variability in optimal sucrose concentration could be attributed to consistent differences among individuals while much less variability was attributable to differences in Methods, test Locations or Stimuli. These results demonstrate convergent validity between measures of preference and liking, support testing at home to lower participant burden, and suggest that aqueous solutions can be useful proxies for some commonly consumed beverages for measuring individual differences.

Polydiacetylene (PDA) inserted in films or in vesicles have received increasing attention due to PDA property to undergo a blue-to-red colorimetric transition along with a change from non-fluorescent to fluorescent upon application of various stimuli. In this review paper, the principle of the detection of various microorganisms (bacteria: directly detected or detected through the emitted toxins or through their DNA, and viruses) and of antibacterial and antiviral peptides based on these responsive PDA vesicles are detailed. The obtained analytical performances, when vesicles are in suspension or immobilized, are given and compared to those of the responsive vesicles mainly based on the vesicle encapsulation method. Many future challenges are then discussed.

Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix-loop-helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 can heterodimerize with ARNTL in the activating limb of the transcriptional/translational feedback loop operating the circadian clock circuitry. NPAS2 can functionally substitute for the core transcription factor and histone/protein acetylase CLOCK in the molecular clockwork endowing central oscillators in the suprachiasmatic nuclei of hypothalamus as well as in peripheral oscillators in the cell of other body tissues, such as the liver and kidney.

Water pollution is the main problem in the current scenario which is being faced by mankind due to the industrial and commercial effects. Industrial effluents contain heavy metals and inorganic ions like nitrates and phosphate ions. These ions are being included in waterways through industrial runoff. When the concentration of these hazardous pollutants increases in aquatic flora and fauna causes severe health problems. So remediation of these toxicants from water reserves is of chief importance. Conventional processes along with modern processes are being used for the treatment of industrial wastes. Photo-degradation is a modern method used for the degradation of inorganic ions due to its environmentally friendly nature and cost-effectiveness. In a recent study Aluminum oxide (Al2O3) nanoparticles were synthesized via a green approach at different pH by using Cymbopogan citratus (lemongrass) plant extract and these nanoparticles were used for the removal of inorganic ions from wastewater. The nanoparticles of different pH showed different % degradation of the inorganic ions in acidic medium removal of inorganic waste was less, in basic media % degradation was more as compared to acidic media but maximum % degradation was observed in neutral media like that average % degradation 91% and 81% was observed for nitrate and phosphate ions. The maximum absorbance occurred at 212nm and Al2O3 nanoparticles showed absorbance from 210nm-217nm. The R2 values of pseudo1st, 2nd, and BMG models were 0.956, 0.837, 0.7007 0.95, 0.896, and 0.756 for the nitrate and phosphate ions. Characterizations of synthesized particles were investigated by using UV-visible spectroscopy and other analytical methods like X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The statistical analyses were done using Simple Linear regression (SLR).

Tinnitus is a heterogeneous auditory disorder without a pharmacological cure but with several palliative treatments. One of the most applied treatments for tinnitus relief combines counselling with sound therapy. The efficiency of this sound therapy depends on the type of sound stimulus and the exposition time. The fundamentals of a customized sound therapy that stimulates the auditory system with a continuous or sequential sound which compensates for the subject hearing loss are described here. A sample of 137 tinnitus subjects are treated with this sound therapy, named Enriched Acoustic Environment. 90% of these patients achieved a clinically relevant and statistically significant tinnitus-related distress relief quantified as a mean drop of their Tinnitus Handicap Inventory score of 24.3 points. These subjects exposed with sequential stimuli (31%) achieved greater distress relief (5.1 points more in their Tinnitus Handicap Inventory score) than those stimulated with continuous sound (69%). Therefore, this sound constitutes an optimized stimulus for tinnitus treatment.

Cancer is a highly heterogeneous disease and remains a global health challenge affecting millions of human lives worldwide. Despite advancements in conventional treatments like surgery, chemotherapy, and immunotherapy, the rise of multidrug resistance, tumor recurrence, and severe side effects necessitates innovative therapeutic approaches. The complex nature of the tumor microenvironment (TME) further compromises the efficacy of traditional chemotherapy drugs. Recently, stimulus-responsive nanomedicines designed to target TME characteristics (e.g., pH, redox, enzymes) have gained attention for their potential to enhance anticancer efficacy while minimizing adverse effects. Among various nanocarriers, hydrogels are an interesting class of nanocarriers used in cancer therapy due to their high water content, adjustable mechanical characteristics, and ability to respond to external/internal stimuli. These properties make hydrogels an ideal nanocarrier for controlled drug release within the TME. This review comprehensively surveys the latest advancements in stimulus-responsive hydrogels for cancer therapy, exploring various stimuli-responsive mechanisms, including biological (e.g., pH, redox), chemical (e.g., enzymes, glucose), and physical (e.g., temperature, light), as well as dual- or multi-stimuli responsiveness. This review will offer novel perspectives on the development of stimulus-responsive hydrogels for cancer therapy.

Surround modulation is a phenomenon whereby costimulation of the extra-classical receptive field and classical receptive field would modulate the visual responses induced individually by classical receptive field. However, there lacks systematic study about surround modulation properties existing in avian optic tectum. In this study, neuronal activities are recorded from pigeon optic tectum, and the responses to moving and flashed squares and bars of different sizes are compared. The statistical results showed that most tectal neurons presented surround suppression as stimuli size grew larger both in moving and flashed paradigms, and the suppression degree induced by larger flashed square was comparable with that by moving one when it crossed near the cell’s RF center, which corresponds to fully surrounding condition. The suppression degree grew weaker when the stimuli move across the RF border, which corresponds to partially surrounding condition. Meanwhile, the fully surround suppression induced by flashed square was also more intense than partially surrounded by flashed bars. The results provide new insight for understanding the spatial arrangement of lateral inhibitions from feedback or feedforward streams, which would help to make clear the generation mechanism of surround modulation found in avian optic tectum.

Cells receive external stimuli to incur structural and functional damages. On scanning acoustic microscopy (SAM), speed-of-sound (SOS), attenuation-of-sound (AOS), and thickness values are plotted on the screen to create cellular images, which are related to stiffness, viscosity, and cell size, respectively. The obtained digital data compared using statistical analysis. We aimed to investigate the effects of anticancer drugs, acidic fluids, and heat effects on the cells by using SAM. Anticancer drug cisplatin induced cancer cell apoptosis/necrosis and regeneration in culture, causing elevated SOS, reduced AOS, and thickness. During a more prolonged incubation, the SAM values fluctuated differently between the cisplatin-treated and untreated cells. The tannic and acetic acid and microwave stimuli induced SOS and AOS elevations. These stimuli altered the cell size, number, differentiation, viscosity, and stiffness, which corresponded well to the fluctuation of the SOS and AOS values after incubation. Different anticancer drugs interacted with cancer cells to induce the characteristic alterations of the SAM values. These structural and mechanical alterations induced in cells was difficult to observe on light microscopy. Cellular damages were statistically compared between different stimuli and time-lapse cellular changes were observed using a SAM analysis. SAM is a useful modality to evaluate cellular damage.

Over recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimulus. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues or cells, and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved by light irradiation at different wavelengths, either in UV, visible or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics and material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the up-to-date phototriggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.

In Nature, it is common for living plants and non-living plant tissues to consist of materials with anisotropic multilayer and non-homogenous structure. The structure of tissues determines their self-shaping and self-folding capabilities in response to a stimulus in order to activate different functionalities. Predetermined movements are realized according to changes in environmental conditions, which trigger the fibrous anisotropic structure of the plants’ material. In this study, we present the fabrication process of low-cost anisotropic multilayer materials that are capable of realizing complex movements caused by small temperature changes (<40 ^oC). The mismatch in the thermo-mechanical properties between three or more anisotropic thin layers creates responsive materials that alter their shape owing to the developed internal stresses. Isotropic layers can perform only bending movements, whereas anisotropic multilayer materials can perform bending, twisting or complex combined modes. The movements of the material can be controlled by forming anisotropic homogenous metallic strips over an anisotropic polymer. As a result, inexpensive responsive materials can be developed to passively react to a very broad range of thermal requirements. We studied the major parameters that affect the sensitivity of the developed materials, as well as their failure modes and crack formation under thermal fatigue conditions.

In this paper, a method for the preparation of ultrasound-responsive microgels was developed based on RAFT-HDA dynamic covalent bonding. First, a styrenic cross-linked network was suc-cessfully prepared by DA reaction between phosphoryl dithioester and furan using double-ended BDEPDF as RAFT reagent mediated St polymerization as double-ended dienophile linker and co-polymer of FMA and St as dienophile. Subsequently, the microgel system was constructed by the HDA reaction between phosphoryl disulfide and furan groups using the copolymer of polyethylene glycol monomethyl ether acrylate (OEGMA) and FMA as the dienophore building block and hy-drophilic segment, and the polystyrene pro-dienophile linker as the cross-linker and hydrophobic segment. The number of furans in the dienophile chain and the length of the dienophile linker were regulated by RAFT polymerization to investigate the effects of single-molecule chain functional group degree (f), furan/dithioester ratio (r), and hydrophobic linker length (D) on the microgel system. These microgels can achieve the reversible transformation of materials under force re-sponsiveness, and the steps are simple and adaptive, which are expected to show important po-tential applications in the fields of biomedical materials and adaptive electrical materials.

Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status, playing a crucial role in the clinical therapeutic outcome of conventional treatments and innovative tumor nanomedicines. Scientists, have devoted great effort in conquering the tumor microenvironment (TME) challenges, in respect of effective drug accumulation and activity in tumor site, overcoming the obstacles of abnormal vasculature, dense stroma and extracellular matrix, hypoxia, and pH gradient acidosis. In this conquest, nanomedicines targeting distinct TME features have flourished, in order to increase site specificity and deep penetration, for effective antitumor activity, and further reprogram TME promoting suppression of cancer stem cells and metastasis. Thereby, several successful nanomedicine therapeutics have been under clinical trials, and further applied in clinical practice. Various novel strategies have been employed in preclinical studies and clinical trials, among which nanomedicines based on biomaterial, that have shown great promise in improving the therapeutic efficacy, reducing side effects, and promoting synergistic activity for TME targeting. In this review, we have focused on the targeting mechanisms for solid TME by nanomedicines based on the application of natural and synthetic biomaterials. We have described critical formulations that have been considered for the design of stimuli-responsive nanomedicines for TME. The development of such systems, has significantly advanced the application of biomaterials, in combinational therapies and in immunotherapies, for improved effectiveness.

Stimuli-responsive polymeric materials have attracted significant attentions in a variety of high-value-added and industrial applications during the past decade. Among various stimuli, light is of particular interest as a stimulus due to its unique advantages such as precisely spatiotemporal control, mild conditions, ease of use, and tunability. In recent years, a lot of effort toward synthesis of biocompatible and biodegradable polypeptide has resulted in many examples of photo-responsive nanoparticles. Depending on the specific photochemistry, those polypeptide derived nano-assemblies are capable of crosslinking, disassembling, or morphing into other shapes upon light irradiation. In this mini-review, we aim to assess the current state of photo-responsive polypeptide based nanomaterials. First, those “smart” nanomaterials will be categorized by their photo-triggered events (i.e., crosslinking, degradation, and isomerization) which are inherently governed by photo-sensitive functionalities including o-nitrobenzyl, coumarin, azobenzene, cinnamyl, and spiropyran. In addition, the properties and applications of those polypeptide nanomaterials will be highlighted as well. Finally, the current challenges and future directions of this subject will be evaluated.

A heterobifunctional reactive oxygen species (ROS)-responsive linker for directed drug assembly onto and delivery from a quantum dot (QD) nanoparticle carrier was synthesized and coupled to doxorubicin using EDC/sulfo-NHS coupling. The doxorubicin conjugate was characterized using ¹H NMR and LC-MS and subsequently reacted under conditions of ROS formation (Cu²⁺/H₂O₂) resulting in successful and rapid thioacetal oxidative cleavage which was monitored using ¹H NMR. The deprotected amine linker is amenable to peptide or protein conjugation prior to QD assembly or to direct conjugation to cognate reactive groups on ligands that cap the QD surface.

Neural precursors (NPs) present in the hippocampus can be modulated by several neurogenic stimuli including environmental enrichment (EE) and antidepressant treatment acting through BDNF-TrkB signaling. We have recently identified NPs in meninges, however menigneal niche response to pro-neurogenic stimuli has never been investigated. To this aim, we analyzed the effects of 4 weeks fluoxetine administration or 1 week EE treatment on NP distribution in mouse brain meninges. Following neurogenic stimuli, although we did not detect modification of meningeal cell number and proliferation, we observed, in meninges, an increased number of β3-Tubulin⁺ immature neuronal cells. Lineage-tracing experiment confirmed that EE-induced β3-Tubulin⁺ immature neuronal cells present in meninges originated from GLAST⁺ radial glia cells. To investigate the molecular mechanism responsible for this response, we studied the BDNF-TrkB interaction. Treatment with ANA-12, a TrkB non-competitive inhibitor, abolished the EE-induced increase of β3-Tubulin⁺ immature neuronal cells in meninges.Overall these data showed, for the first time, that the meningeal niche responded to neurogenic stimuli by increasing the immature neuronal population through TrkB-mediated signaling. A better understanding of the neurogenic stimuli effects on NPs in meninges may be useful to improve the effectiveness of depression and mood disorders treatments.

In recent years, cancer therapy has witnessed significant advancements, with a focus on personalized and targeted treatment strategies. One promising approach involves the use of stimuli-responsive biomaterials for site-specific drug release. Among these biomaterials, pH, and redox-triggered polymer-nano composites have gained immense attention due to their ability to respond to the specific tumor microenvironment, enhancing therapeutic efficacy while reducing off-target effects. Cancer cells often exhibit anomalous biochemical properties, attributed to lower cytosolic pH (acidic) and elevated redox potential through the epitomized upregulation of undesired genes. Such biological process substantially imbalance the level ions (protons) and biological thiols glutathione (GHS) in the cytoplasm as well as in the subcellular organelles. Superfluous accumulation of ions and redox imbalance is associated with proliferation, invasion, and growth of tumor. Because of high surface area, deep tissue penetration capability, higher hydrophilicity, hydrophobic interior for drug/gene efficient loading, biocompatibility and site-specific targeting efficiency, functionalized polymer nanocomposites are superior to conventional small molecular materials. Paradoxically conventional methods of drug delivery aided therapeutics accompanied with inherent drug/genes are encapsulated in biocompatible carrier or suitable transfecting agents generally suffered with low bioavailability, uncontrolled drug release, low cellular penetration, cellular internalization, toxicity, and poor drug loading efficiency. To overcome these issues, recently various multifunctional nanomaterials were developed, based on synergistic stimuli responsive aided drug release in a specified cellular or subcellular system. High therapeutic efficacy, of nanoparticles (NPs) mainly associated with surface functionalization through biocompatible polymeric materials, site-specific targeting units accompanied with stimuli responsive components. Followed by therapeutically important drug or genetic materials were loaded into NPs either in covalent or non-covalent approach. Intriguingly, combined pH and redox dual stimuli based functional materials specially based on polymeric nanocomposites for cancer therapeutics scarcely reported. This article provides the recent progress in pH and redox-responsive polymer-nano composites for site-specific drug delivery in cancer therapy. It explores design principles, fabrication methods, mechanism of action, and prospects of these dual-stimuli responsive biomaterials.

Patients with lean NAFLD make up an increasing subset of liver diseases. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and nonlean patients. The study comprised 606 adults from the community, stratified into lean or nonlean (BMI </≥ 24 kg/m2) and NAFLD or non-NAFLD (scoring of ultrasonographic fatty liver indicator, US-FLI ≥ 2/<2). Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD among the tertiles of fetuin-A after adjustment. The least square means were computed by general linear models to estimate marginal means of the serum fetuin-A concentrations in relation to the NAFLD groups. The OR of having NAFLD for the highest versus the lowest tertile of fetuin-A was 2.62 (95% CI: 1.72-3.98; P for trend<0.001). Stratifying by BMI, the OR of having lean NAFLD for the highest versus the lowest tertile of fetuin-A was 2.09 (95% CI: 1.09-3.98; P for trend 0.026), while nonlean NAFLD had no significant association with the fetuin-A gradient after adjustments. Fetuin-A was positively associated with lean NAFLD after adjusting for central obesity and insulin resistance.

innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan can be used to create biocompatible and biodegradable scaffolds with 3D architectures similar to human structures, allowing their efficient and safe use as tissue engineering and drug delivery systems in chronic wounds. Locally heated tumors above polymer lower critical solution temperature can induce its conversion into a hydrophobic form, enhancing drug release until the thermal stimulus is gone, where a lower release is due to the swelling of the material. This paper integrates the relevant reported contributions of bioengineered scaffolds for thermo-responsive drug delivery in wound healing. Therefore, we present a comprehensive review that aims to demonstrate the capacity of these systems to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D-printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to the patient’s convenience, as well as reduce drug toxicity and side effects.

The purpose of the present study was to investigate the effect of the laterally moving tactile stimuli to the sole on the anticipatory postural adjustment (APA) of the gait initiation. Thirteen healthy males participated in this study. A sound cue was provided at the beginning of each trial. The moving tactile stimuli were delivered to the sole after the start cue. The loci of the tactile stimuli moved from the left to right most side of the sole, and then moved from the right to left most side of that in a stimuli cycle. The duration of one stimuli cycle was 960 ms, and this cycle repeated 16 times in a trial. The participants made three steps forward from quiet stance at the participants' preferred time after the start cue. The APA did not onset at the specific direction or phase of the moving tactile stimuli, indicating that they did not use the stimuli as a trigger for initiating the gait. The moving tactile stimuli decreased the amplitude and increased the duration of the APA. The moving tactile stimuli increased the time between the APA onset and toe-off of the initial support leg, indicating that they moved slower when initiating gait during the moving tactile stimuli. Those findings are explained by the view that suppression of the APA induced by the moving tactile stimuli to the sole is caused by the decrease in the velocity of the gait initiation, and the slower velocity of the gait initiation is caused by masking tactile sensation of the sole.

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol-gel transition. We started with the synthesis of three cationic azobenzenes (AZO A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV-Vis and ¹H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel-sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels.

Temperature-responsive separation membranes can significantly change their permeability and separation properties in response to changes in their surrounding temperature, improving efficiency and reducing membrane costs. This study focuses on the modification of commercial polyvinylidene fluoride (PVDF) membranes with amphiphilic temperature-responsive copolymer and inorganic nanoparticles. We prepared an amphiphilic temperature-responsive copolymer which the hydrophilic poly(N-isopropyl acrylamide) (PNIPAAm) was side-linked to a hydrophobic polyvinylidene fluoride (PVDF) skeleton. Subsequently, PVDF-g-NIPAAm polymer and graphene oxide (GO) blended with PVDF to prepare temperature-responsive separation membranes. The results showed that temperature-responsive polymers with different NIPAAm grafting ratios were successfully prepared by adjusting the material ratio of PVDF to NIPAAm. PVDF-g-NIPAAm was blended with PVDF with different grafting ratios to obtain separate membranes with different temperature responses. GO and PVDF-g-NIPAAm formed a relatively stable hydrogen bond network, which improved the internal structure and mechanical properties of the membrane without affecting the temperature response, thus extending the service life of the membrane.

Bovine lactoferrin (bLf) is a milk-derived protein that exhibits multiple biological activities and has been explored towards different therapeutic applications. Since this molecule is susceptible to degradation and some of its properties depend on its tertiary structure, the encapsulation of bLf in stimuli-responsive therapeutic formulations provides an added value to potentiate its biological activities when administered. Plasmonic magnetoliposomes emerge as promising nanosystems for dual hyperthermia (magneto-photothermia) and local therapy, since the combination of magnetic and gold nanoparticles (NPs) in a single nanosystem (multifunctional liposomes) enables the targeting and controlled release of encapsulated drugs. In this work, plasmonic magnetoliposomes (PMLs) containing manganese ferrite nanoparticles (28 nm size) and gold nanoparticles (~ 5 nm size) functionalized with 11-mercaptoundecanoic acid or octadecanethiol, were synthesized and loaded with bLf. The structural, magnetic and optical properties of the nanoparticles were measured by TEM, SQUID and UV/vis/NIR absorption spectroscopy. Specific Absorption Rate was determined to assess the capabilities for magnetic and photothermal hyperthermia. Finally, Saccharomyces cerevisiae was used as an eukaryotic cellular model to assess the biological activity and the mechanism of entry of bLf-loaded PMLs, through counting of colony forming units and fluorescence microscopy, respectively. The results demonstrate that PMLs are mainly internalized through an energy- and temperature-dependent endocytic process, though the contribution of a diffusion component cannot be discarded. Most notably, only bLf-loaded PMLs exhibit cytotoxicity with an efficiency similar to free bLf, attesting their promising potential for bLf delivery in the context of therapeutic interventions.

Diatomite (DME) consists of natural ordered porous structures that are excellent candidates as microcontainers. However, to the best of our knowledge, the application of DME loaded with corrosion inhibitors in anti-corrosion coatings has not hitherto been reported. In this study, DME has been used as a source of microcontainers to load benzotriazole (BTA) inhibitor by an immersion method. In order to prevent unwanted early release of the small molecule BTA inhibitor from the DME microcontainers, inspired by the adhesion characteristics of catechol and amine in mussel adhesion protein, polydopamine (PDA) was coated on their surfaces to generate BTA@DME/PDA microcapsules. Because of the depolymerization characteristics of PDA at low pH, the synthesize microcapsules showed a controllable release function. The SEM morphology, chemical structure, and loading capacity of the synthesized BTA@DME/PDA microcapsules were characterized. The corrosion resistances of epoxy coatings with different contents of BTA@DME/PDA microcapsules were compared by saline immersion and electrochemical impedance tests. A scratched coating with 5wt.% BTA@DME/PDA microcapsules showed the best anti-corrosion effect.

Drought and salinity are among the most important abiotic stress factors that limit the productivity in economically important plants. Although genes from wild relatives or unadapted germplasm have often been used for stress tolerance breeding, only few studies have examined wild relatives to understand the genetic and molecular basis of stress tolerance. In this study, we monitored the changes in gene expression profiles of leaf and root tissues of two wild barleys (Hordeum spontaneum L.) accessions from Israel after treatment with salt (NaCl) and drought (PEG) stress. We identified a total of 641 differentially expressed genes across 24 conditions (2 accessions, 2 stress conditions, 2 tissues and 3 time points). Our gene expression analyses revealed large numbers of differentially expressed genes in different accessions by different stress treatments. In addition, the number of genes altered in the leaves of stress-exposed plants of both genotypes was higher than those altered in the roots. Interestingly, there was a relatively little overlap between the leaf and the root stress-responsive gene expression patterns, suggesting that different stress-associated processes might be operating in these tissues during stress adaptation. Overall, our results revealed a number of candidate genes and plant processes associated with stress tolerance in wild barley. Wild barley would be a useful source of new genetic variation for drought and salt stress tolerance. Our results could provide new insights into the mechanisms of drought and salt stress tolerance in wild barley and should be useful for genetic improvement of salt-drought tolerance in cultivated barley.

The long-term impact of treatment of dogs with steroid-responsive enteropathy (SRE) on the fe-cal microbiome and metabolome has not been investigated. Therefore, this study aimed to evaluate the fecal microbiome and metabolome of dogs with SRE before, during, and following treatment with standard immunosuppressive therapy and an elimination diet. We retrospec-tively selected samples from 9 dogs with SRE enrolled in a previous clinical trial, which received treatment for 8 weeks, and had achieved remission as indicated by the post-treatment clinical scores. Long-term (1 year) samples were obtained from a subset (5/9) of dogs. Samples from 13 healthy dogs were included as controls (HC). We evaluated the microbiome using 16S rRNA sequencing and qPCR. To evaluate the recovery of gut function, we measured fecal metabolites using an untargeted approach. While improvement was observed for some bacterial taxa after 8 weeks of treatment, several bacterial taxa remained significantly different from HC. Seven-ty-five metabolites were altered in dogs with SRE, including increased fecal amino acids and vitamins, suggesting malabsorption as a component of SRE. One year after treatment, however, all bacterial species evaluated by qPCR and 16S rRNA gene sequencing, and all but thirteen me-tabolites were no longer different from healthy controls.

Alfalfa, an important legume forage, is an ideal crop for sustainable agriculture and a potential bioenergy plant. Drought, one of the most common environmental stresses, substantially affects plants’ growth, development and productivity. MicroRNAs (miRNAs) are newly discovered gene expression regulators that have been linked to several plant stress responses. To elucidate the role of miRNAs in drought stress regulation of alfalfa, a high-throughput sequencing approach was used to analyze 12 small RNA libraries comprising of 4 samples, each with 3 biological replicates. We identified 348 known miRNAs, belonging to 80 miRNA families, from the 12 libraries and 281 novel miRNAs using Mireap software. 18 known miRNAs in roots and 12 known miRNAs in leaves were screened out as drought-responsive miRNAs. Except for miR319d and miR157a which were upregulated under drought stress, the expression pattern of drought-responsive miRNAs were different between roots and leaves in alfalfa. This is the first study discovering miR157a, miR1507, miR3512, miR3630, miR5213, miR5294, miR5368 and miR6173 are drought-responsive miRNAs. Target transcripts of drought-responsive miRNAs were computationally predicted. All 447 target genes for the known miRNAs were predicted using an online tool. This study provides a significant insight on understanding drought-responsive mechanisms of alfalfa.

Using structured light to drive colloidal motors, due to its advantages of remote manipulation, energy tunability, programmability, and controllability of spatiotemporal distribution, has been attracting much attention in the fields of targeted drug delivery, environmental control, chemical agent detection, and smart device design. Here, we focus on studying the group control of colloidal made from a photo-responsive organic polymer molecule NO-COP (N,O-Covalent organic polymer). These colloidal motors mainly respond to the light intensity patterns. We chose a digital micromirror device (DMD) to modulate the structured light field shining on the sample, by considering its merit of fast refreshing speed, good programmability, and high-power threshold. It is found that under ultraviolet or green light modulation, such colloidal motors exhibit various group behaviors including group diffusion, group patterning, and group migration. The qualitative interpretation is also provided for these observations.

In hospitals and smart nursing homes, ambient-intelligent care rooms are equipped with many sensors. They can monitor environmental and body parameters, and detect wearable devices of patients and nurses. Hence, they continuously produce data streams. This offers the opportunity to collect, integrate and interpret this data in a context-aware manner, with a focus on reactivity and autonomy. However, doing this in real-time on huge data streams is a challenging task. In this context, cascading reasoning is an emerging research approach that exploits the trade-off between reasoning complexity and data velocity by constructing a processing hierarchy of reasoners. Therefore, a cascading reasoning framework is proposed in this paper. A generic architecture is presented allowing to create a pipeline of reasoning components hosted locally, in the edge of the network, and in the cloud. The architecture is implemented on a pervasive health use case, where medically diagnosed patients are constantly monitored, and alarming situations can be detected and reacted upon in a context-aware manner. A performance evaluation shows that the total system latency is mostly lower than 5 seconds, allowing for responsive intervention by a nurse in alarming situations. Using the evaluation results, the benefits of cascading reasoning for healthcare are analyzed.

The early 2-factor (E2F) family of transcription factors, including E2F1-8, plays a critical role in apoptosis, metabolism, proliferation, and angiogenesis within glioblastoma (GBM). However, the specific functions of E2F transcription factors (E2Fs) and their impact on the malignancy of Bevacizumab (BVZ)-responsive GBM subtypes remain unclear. This study used data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to explore the impact of eight E2F family members on the clinical characteristics of BVZ-responsive GBM subtypes and possible mechanisms of recurrence after BVZ treatment.To predict the possibility of GBM patient survival and progression, we classified and comparedthe expression of E2Fs according to BVZ-responsive subtypes and employed a machine learning method-TreeBagger, one random forest algorithm. Multiple bioinformatics analyses have shown that the significant increased E2F8 post BVZ treatment may enhance the function of angiogenesis and stem cell proliferation, indicating one of the mechanisms of GBM recurrence after treatment. In addition, BVZ treatment in unresponsive GBM patients may potentially worsen disease progression. Our findings suggest that E2F family members play important roles in GBM malignancy and BVZ treatment response, highlighting their potential as prognostic biomarkers and therapeutic targets and recommending precise BVZ treatment for GBM patients.

Bone fractures are very common in the geriatric population and poses a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing. However, there remains several impediments to achieving the desired healing outcomes. Injectable hydrogels have become attractive scaffold materials for bone regeneration given their high performance in filling irregularly sized bone defects, ability to encapsulate cells and bioactive molecules, and mimic the native ECM of bone. We investigated the use of an injectable chitosan-based hydrogel scaffold to promote differentiation of preosteoblasts in vitro. The hydrogels were characterized by evaluating cell homogeneity, cell viability, rheological and mechanical properties, and differentiation ability of preosteoblasts in hydrogel scaffolds. Cell-laden hydrogel scaffolds exhibited shear thinning behavior and the ability to maintain shape fidelity after injection. The CNC-CS hydrogels exhibited higher mechanical strength and significantly upregulated the osteogenic activity and differentiation of preosteoblasts as shown by ALP activity assays and histological analysis of hydrogel scaffolds. These results suggest that this injectable hydrogel is suitable for cell survival, can promote osteogenic differentiation of preosteoblasts, and structurally support new bone growth.

The paradigm of drug delivery via nano- and microcarriers is one of the leading ideas that enable overcoming the limitations of traditional chemotherapy. The trend toward more complex drug carriers capable of multifunctionality is observed in the literature. To date, prospects of stimuli-responsive systems to control the cargo release in the lesion nidus are widely accepted. Both endogenous and exogenous stimuli are employed for this purpose, however, endogenous pH is one of the most common triggers. Unfortunately, scientists face difficulties in the implementation of this idea since a range of biological barriers, drug bioavailability issues, and challenges in the synthesis of carriers with required properties have arisen. Here, we discuss fundamental strategies of pH-responsive drug delivery as well as limits in its application and reveal the main problems, weak sides, and reasons for poor clinical results. Also, we have made an attempt to formulate the profiles of "ideal" drug carrier in the frame of different strategies and considered recently published studies through the lens of these profiles. This approach enables the identification of current trends and promising vectors in the development of pH-responsive drug delivery systems, as well as challenges to be resolved in the next generation of carriers.

Currently, the most promising work seems to be aimed not so much at the development of new drugs, but rather at creating ways of targeted delivery of existing drugs. In this paper, we show that polymeric micelles based on chitosan, heparin grafted with lipoic and oleic acids residues demonstrate the potential for doxorubicin delivery to tumors due to pH-, glutathione-sensitivity. Smart delivery systems use the Aikido principle, i.e. they target tumor cells according to their features. Natural polysaccharides (heparin and chitosan) provide the pH sensitivity of micelles: the release of doxorubicin (Dox) is enhanced in a slightly acidic environment (model tumor microenvironment). Fatty acid residues are necessary for the formation of micelles and solubilization of cytostatics in a hydrophobic core. Lipoic acid residues formed a labile S-S cross-linking between polymer chains (the first method), and also covalently attached doxorubicin molecules through glutathione-sensitive S-S bridges (the second option) – determine Redox sensitivity of micelles to tumors. The characterization of polymeric micelles and prodrugs (Dox-polymer) was carried out using FTIR spectroscopy. The release of doxorubicin from micelles occurs slowly (20% / 6h) in an environment with a pH of 7.4 and the absence of glutathione, while in a slightly acidic environment and in the presence of 10 mM glutathione, the rate increases up 6 times, with an increase in the effective concentration up to 5 times after 7 h. The permeability of free doxorubicin, micellar formulations (covalent S-S crosslinked and not) into Raji, K562, A875 cancer cells was studied using confocal laser scanning microscopy (CLSM), demonstrated an increase in the permeability of micellar formulations based on Dox. Thus, we have presented micellar formulations of doxorubicin for targeted delivery to tumor, what is important in the aspects of reducing non-target toxicity, increasing the selectivity of cytostatics against tumors and overcome multidrug resistance.

Plants have a natural protective process of altering their genetic molecules in response to changing environments. To uncover the genetic potential of plants, it is crucial to understand how they adapt to adverse conditions by analyzing their genetic molecules. In the study, we focused on understanding the responsive genes of tomatoes under drought conditions. We analyzed RNASeq data from different Tomato genotypes, tissue types, and different drought durations. We used a time series scale to identify early and late drought-responsive gene modules and applied a machine learning method to identify the best responsive genes. We found six candidate genes of Tomato (ASCT, FLA2, BAG5, DCL2b, NFP7.3, and ADC1) that were responsive to drought. We further constructed their protein-protein interaction network to identify their potential interactors and found them drought responsive proteins. The candidate genes can help to explore the adaptation of tomato plants under drought conditions. The identification of these candidate genes and modules can have far-reaching implications for molecular breeding and genome editing in Tomato, providing insights into the molecular mechanisms that underlie drought adaptation. This research underscores the importance of the genetic basis of plant adaptation, particularly in changing climates and growing populations.

The disruption of conventional manufacturing, supply, and distribution channels for medical supplies during the COVID-19 pandemic has caused widespread shortages and catalyzed local efforts to use nontraditional, rapid manufacturing to meet urgent healthcare needs. Here we present a crisis-responsive design framework designed to assist with product development under pandemic conditions. The framework utilizes extensive stakeholder engagement, comprehensive and dynamic needs assessment, local manufacturing, and product testing for the accelerated development of healthcare products. We contrast this framework with traditional medical device manufacturing and discuss relevant regulatory policies. We highlight the applicability of the crisis-responsive framework to a successful local program that designed and supplied face shields for a large US academic hospital. Finally, we make recommendations aimed at improving future resilience to healthcare emergencies. These include continued development of open source designs suitable for rapid manufacturing and changes in regulatory policy that strike a balance between rigidity and uncontrolled innovation.

Various kinds of primary metabolisms in plants are modulated through sulfate assimilation that the uptake of this inorganic compound can be regulated via the sulfate transporters, such as sulfotransfer-ases (SOTs), engaged in the sulfur metabolism. In the current study a genome-wide approach has been utilized for recognition and characterization of SOT family genes in the significant nutritional crop po-tato (Solanum tuberosum L.). As a result, 29 StSOT genes were identified in the potato genome, which were mapped onto the nine S. tuberosum chromosomes. The protein motifs structure demonstrated two highly conserved 5' PSB region and 3' PB motif that are essential for sulfotransferase and catalytic ac-tivities. The protein-protein interaction networks also significantly demonstrated an interesting collabo-ration between SOTs and the other genes, such as PRTase, APS-kinase, protein phosphatase and APRs, in sulfur compounds biosynthesis and regulation of the flavonoid and brassinosteroid metabolic pro-cesses, which clearly detected the importance of sulfotransferases for potato proper growth/development and stress dealing. Notably, the homology modeling of StSOT proteins and dock-ing analysis of their ligand-binding sites revealed the presence of some stress-responsive residues, such as proline, glycine, serine and lysine, in their active sites. The expression assay of StSOT genes via the potato RNA-seq data clearly suggested the engagements of these gene family members in plants growth and extension as well as responses to various hormones and biotic/abiotic stimulus circum-stances. Our predictions can be informative for the functional characterization of the SOT genes in po-tato and may the other nutritional crops.

The practical application of a pH-responsive Nanoparticle Drug Delivery System (NDDS) in cancer treatment is often hampered by several issues such as the protection of therapeutic molecules from external stresses, inefficient targeted delivery, sustained drug release, and poor efficacy. This study presents an effective design strategy for the synthesis of a pH-sensitive controlled hydrophobic drug delivery method based on the formulation of chitosan (CS)-coated mesoporous silica nanoparticles (MSNs) through the sol-gel method, where hydrolysis takes place in the acidic medium followed by polycondensation of the hydrolyzed products. For this purpose, NH2 modified-MSNs were prepared by using tetraethyl orthosilicate (TEOS) as precursor and cetyltrimethylammonium bromide (CTAB) as a template, and 3-aminopropyltriethoxysilane (APTES) for amine modification, followed by hydrophobic drug loading and CS coating of various concentrations. Camptothecin (CPT) was used as a model drug. Fabricated monodispersed functionalized nanoparticles had sizes ranging from 200nm to 245nm with an encapsulation efficiency as high as 90%. The highest encapsulation efficiency was found for 1% CS coating, which released 50% drug in 120h at pH 6.4 and 20% at pH 7.4 respectively. These nanoformulations exhibited pH-responsive release patterns of CPT under two different pH values (pH=7.4 and pH=6.4). These results contribute to the optimization of NDDS, with potential implications for nanoformulations designed for controlled and sustained drug release particularly to tumors without affecting healthy cells owing to differences in the pH of the tumor microenvironment and the normal physiological environment of cells.

With the breakthroughs and innovative developments in nanotechnology, research on the application of nanomedicine in cancer therapy has so far seen tremendous expansion and success. Intelligent stimulus-responsive nanocarriers are an emerging field of research and have great interest in cancer therapy owing to the fascinating properties such as excellent targeting function, high drug loading capacity, and targeted on-demand release properties. Responsive nanomaterials can be designed and constructed according to the dosing context and therapeutic needs, at the same time, activated by internal bio-stimuli (pH, redox, and enzymes) and/or external stimuli (ultrasound, light, temperature, and magnetic), respectively. What’s more, smart nanocarriers are also utilized for the precise and controllable release of antitumor drugs from cancer tissues and cells to achieve efficient diagnosis and treatment of tumors. Deeply investigated, responsive nanocarriers have attracted considerable attention due to their ability to release precisely at tumor-specific sites. Herein, we review the recent advances of novel stimuli-responsive nanocarriers in the field of cancer therapy. Finally, the challenges and application prospects of smart nanocarriers are further elaborately discussed.

Given the many approaches to and definitions of gender responsive monitoring and evaluation (M&E) for health programs and interventions there is a lack of clarity on how to operationalize it including what to measure and how to measure it. We conducted a scoping review to understand what makes M&E gender responsive. We included 31 studies and conducted two rounds of extraction to delineate ways in which gender was integrated into M&E. Twelve articles described the use of theory to guide M&E though most were not related to gender. Twelve articles employed a gender score in data collection, most of which measured Likert scale responses related to gender equity. Even though most studies did not use a specific gender framework, most incorporated gender domains in their analysis. Seven studies used participatory methods in the design and implementation of M&E. Most studies conducted M&E on programs or interventions that were designed to be gender intentional and related to gender issues. Gender responsive M&E intentionally integrates gender into the M&E process, regardless of how gender-intentional the program or intervention is. Gender dimensions can be identified through gender theories, models, scores, and frameworks to inform tool development, data collection, analysis, and stakeholder engagement processes.

The cross-linkable PCL-PEG analogues block-graft copolymer was designed and synthesized, which with the copolymer of the MEO₂MA and OEGMA as graft chains to improve the mPEG-b-PCL-b-mPEG copolymer the aqueous solution properties. And successfully prepared two hydrogels via a copper-catalyzed 1, 3-dipolar azide-alkyne cycloaddition reaction of alkyne-terminated poly[glycidyl methacrylate-co-2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate] [P(GMA-co-MEO₂MA-co-OEGMA)] with azide end-functionalized PCL-PEG analogues block-graft copolymer, and tetrakis (2-propynyloxymethyl) -methane (TPOM) and with azide end-functionalized PCL-PEG analogues block-graft copolymer. The copolymer's chemical structure was characterized by proton nuclear magnetic resonance spectroscopy and fourier transform infrared spectroscopy. The molecular weights of the copolymers were decided with gel permeation chromatography. The water solubility and temperature sensitivity of the copolymers were studied by taking digital photos and transmittance change measured by UV spectrophotometer at different temperatures. Fluorescence probes, surface tension, dynamic light scattering and transmission electron microscopy were used to analyze the micelles that copolymers self-assembly in aqueous solution. The sol-gel behavior of copolymer solutions at high concentrations was explored by vial inversion experiments. Finally, the network structure of the gels was observed by scanning electron microscopy. These conclusions indicate that these hydrogels are expected to be used as a new material in the field of biomedicine.

In organisms that use reduced sulfur compounds as alternative or additional electron donors to organic compounds, transcriptional regulation of genes for enzymes involved in sulfur oxidation is needed to adjust metabolic flux to environmental conditions. However, little is known about the sensing and response to inorganic sulfur compounds such as thiosulfate in sulfur-oxidizing bacteria. In the Alphaproteobacterium Hyphomicrobium denitrificans, one strategy is the use of the ArsR-SmtB-type transcriptional regulator SoxR. We show that this homodimeric repressor senses sulfane sulfur and that it is crucial for the expression not only of sox genes encoding the com-ponents of a truncated periplasmic thiosulfate-oxidizing enzyme system but also of several other sets of genes for enzymes of sulfur oxidation. DNA binding and transcriptional regulatory activity of SoxR are controlled by polysulfide-dependent cysteine modification. The repressor uses the formation of a sulfur bridge between two conserved cysteines as a trigger to bind and release DNA and can also form a vicinal disulfide bond to orchestrate a response to oxidizing conditions. The importance of the sulfur bridge forming cysteines was confirmed by site directed mutagen-esis, mass spectrometry and gel shift assays. In vivo, SoxR interacts directly or indirectly with a second closely related repressor, sHdrR.

Abstract Background In tumors, somatic mutagenesis presumably drives DNA damage response (DDR) via altered regulatory pathways increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation activated DNA repair pathways of tumors. Purpose Justifying that cancer cells are not enemies to be killed, but rather they are ill human cells having the remnants of physiologic regulatory pathways. Results 1. Genomic instability and cancer development may be originated from the flaw of estrogen signal rather than excessive estrogen signaling. 2. Healthy cells with genomic instability exhibit somatic mutations helping DNA restitution. 3. Somatic mutations in tumor cells aim the restoration of DNA damage rather than further genomic derangement. 4. In tumors, estrogen signal drives the pathways of DNA stabilization leading to apoptotic death. 5. In the peritumoral cellular infiltration, the genomic damage of tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, increased growth factor receptor (GFR) signal confers unliganded activation of estrogen receptors (ERs). 6. In tumor cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signal and consequential apoptosis. In tumors non responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathway, are exhausted leading to farther genomic instability and unrestrained proliferation. Conclusion Understanding the real character and behavior of human tumors at molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy rather than provoking additional genomic damages.

Background and introduction: Lung cancer is a prevalent and deadly disease globally. Non-small cell lung cancer (NSCLC) is the most common subtype, comprising 85% of cases; Case report: A 65-year-old ex-smoker man presented to our facility with nocturnal cough. Various investigations revealed that he had metastatic NSCLC, for which he underwent chemotherapy with cisplatin and gemcitabine, followed by immunotherapy with Nivolumab. He achieved a complete response to the therapy and has remained free from recurrence for over 7 years since the initial diagnosis; Discussion and Conclusion: The treatment of metastatic NSCLC remains a significant therapeutic challenge, but the implementation of new therapeutic techniques has expanded the possibilities of achieving complete and durable eradication of the disease.

Cognitive biases towards disorder-specific stimuli are suggested to be crucial in the development and maintenance of symptoms in adults with functional gastrointestinal disorders (FGID). Functional abdominal pain disorders (FAPD), a subtype of FGID, are common in children and adolescents, but the influence of cognitive biases is sparsely examined. The aim of this study was to 1) develop a new experimental design for assessing cognitive biases towards gastrointestinal stimuli in children and adolescents (age 8-17 years) and 2) test its feasibility on a healthy sample exploring potential sex- and age-related differences. The online experimental design – BY-FAP (Bias in Youth with Functional Abdominal Pain) includes a word task and a picture task. Stimuli in both tasks are related to general and gastrointestinal symptoms and the design includes three phases: 1) encoding, 2) free recall and 3) recognition. Results from 96 healthy participants (Mage = 12.3, 47.9% female) found no significant difference between sex or age groups in recall and recognition of either words or pictures. The results support that the design is feasible for children and adolescents. In the future, BY-FAP can be used to explore possible cognitive biases in children and adolescents with FAPD.

Homogeneous water dispersions of MWCNTs were prepared by ultrasonication in the presence of an amphiphilic polystyrene-block-poly(acrylic acid) (PS-b-PAA) copolymer. The ability of PS-b-PAA to disperse and stabilize MWCTNs was investigated by UV-vis, SEM and zeta potential. It is shown that the copolymer can disperse nanotubes directly by sonication in water. The results show that the addition of a styrene block to PAA enhances the dispersion efficiency compared to pure PAA, possibly due to the nanotube affinity with the polystyrene moiety. Notably, the dispersions show an evident pH-responsive behavior, being MWCNTs reaggregation promoted in basic environment. Furthermore, composites obtained by drop casting display electrical conductivity responsive to pH variations, showing the potential of such materials for sensing applications.

More than 1 million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at late stage, either because lack of symptoms such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV) whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer. uterine cancer, and cervical cancer. AR2011 was also able to strongly inhibit the in vitro growth of ovarian malignant cells obtained from human ascites fluid. The virus could synergize in vitro with cisplatin even on ascites-derived cells obtained from patients heavily pretreated with neoadjuvant chemotherapy. AR2011(h404) a dual transcriptionally targeted derived virus armed with hCD40L and h41BBL under the regulation of the hTERT promoter, showed a strong efficacy in vivo both on subcutaneous and intraperitoneally established human ovarian cancer in nude mice. Preliminary studies in an immunocompetent murine tumor model showed that AR2011(m404) expressing the murine cytokines was able to induce an abscopal effect. The present studies suggest that AR2011(h404) is a likely candidate as a novel medicine for intraperitoneal disseminated ovarian cancer.

Two antimicrobial agents such as silver nanoparticles (AgNPs) and titanium dioxide (TiO2) have been formulated with natural polysaccharides (chitosan or alginate) to develop innovative inks for the rapid, customizable, and extremely accurate manufacturing of 3D printed scaffolds useful as dressings in the treatment of infected skin wounds. Suitable chemical-physical properties for the applicability of these innovative devices were demonstrated through the evaluation of water content (88-93%), mechanical strength (Young’s modulus 0.23-0.6 MPa), elasticity, and morphology. The antimicrobial tests performed against Staphylococcus Aureus and Pseudomonas Aeruginosa demonstrated the antimicrobial activities against Gram+ and Gram– bacteria of AgNPs and TiO2 agents embedded in the CH or ALG macroporous 3D hydrogels (AgNPs MIC starting from 5 µg/ml). The biocompatibility of chitosan was widely demonstrated by cell viability tests and was higher than that observed for alginate. Constructs containing AgNPs at 10 µg/ml concentration level did not significantly alter cell viability as well as the presence of titanium dioxide; cytotoxicity towards human fibroblasts was observed starting with AgNPs concentration of 100 µg/ml. In conclusions, the 3D printed dressings here developed own the features to be cheap, highly defined, easy to be manufactured and further applied in personalized antimicrobial medicine applications.

In this work, thermo-responsive block copolymer brushes modified graphene oxide (GO) nanohybrid was fabricated successfully via the host-guest interaction between β-cyclodextrin functionalized GO and azobenzene-terminated PNIPAM-b-P(St-co-MQ). The block copolymer was synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization based on the monomers of N-isopropylacrylamide (NIPAM), 5-(2-methacryloyl-ethyloxymethyl) -8-quinolinol (MQ), styrene (St) and an azobenzene functional RAFT agent. The 8-hydroxyquinoline units containing in the block polymer can coordinate with CdSe/ZnS quantum dots(QDs) to form a CdSe/ZnS QDs-block copolymer brushes modified graphene oxide fluorescence nanohybrid (QDs/polymer/GO fluorescence nanohybrid) and the resulting fluorescence nanohybrid had a robust temperature responsive property which result from the change in the PNIPAM conformation in the block copolymer on the surface of GO.

The unavoidable progression of EGFR-mutated NSCLC on EGFR-TKIs forces us to discover solutions for further therapies. Herein, we discuss the necessity of accurate genomic mapping of progressive disease illustrated by a patient case. Tumor rebiopsies at progression are strongly needed to characterize acquired resistance to EGFR-TKI. The necessary data, however, may be reliably obtained only by deep targeted next generation sequencing (NGS) of both DNA and RNA. The reported case is a patient with EGFR-mutant NSCLC, who progressed during second line Osimertinib with subsequent targeted treatment determined by the detection of an acquired intergenic ANK3-RET-fusion with concomitant PTEN-mutation and MDM2-amplification. These three acquired gene alterations represent potential mechanisms of TKI-resistance, not previously reported on second line Osimertinib. Yet, while PTEN-mutations and MDM2-amplification are currently undruggable, the ANK3-RET fusion allowed further personalized treatment by combining continuation of Osimertinib with the RET-TKI Pralsetinib, which resulted in objective partial response, so far for 7 months, and significant clinical improvement. Hence, complementary DNA- and RNA-based targeted NGS may be of importance in clinical routine to better reveal the current molecular state of the disease and contribute to the identification of further targeted therapy strategies. Indeed, further cases with acquired RET-fusions, including ANK3-RET, should be investigated to fully determine the effectiveness of RET-TKI-Osimertinib combinations.

Chronic and non-healing wounds demand personalized and more effective therapies for treating complications and improve patient adherence. This work aims to develop a suitable chitosan-based scaffold to provide 24 hours controlled release of DKT, by taking advantage of chitosan’s thermo-responsive behavior as well as local hyperthermia in wounds. Three formulation prototypes were developed using chitosan (F1), 2:1 chitosan: PVA (F2), and 1:1 chitosan:gelatin (F3). Compatibility tests were done by DSC, TG, and IR spectroscopy. SEM was employed to examine the morphology of the surface and inner layers from the scaffolds. In vitro release studies were performed at 32 °C and 38 °C to evaluate the release profiles, which were later adjusted to different kinetic models for the best formulation. F3 showed the most controlled release of DKT at 32 °C for 24 hours (77.75 ± 2.72 %), and reduced the burst release in the initial 6 hours (40.18 ± 1.00 %), while at 38 °C the release reached 88.52 ± 2.07 % at 12 hours. The release profile for this formulation fits with Hixson-Crowell and Korsmeyer-Peppas kinetic models at both temperatures. Therefore, the developed chitosan/gelatin thermo-responsive scaffold provides a suitable system for wound healing with a controlled release of DKT for 24 hour-use, which can overcome adherence issues and wound complications.

Nanosized drug delivery systems (DDS) have been studied as a novel strategy against cancer due to their potential to simultaneously decrease drug inactivation and systemic toxicity and increase passive and/or active drug accumulation within the tumor(s). Triterpenes are plant-derived compounds with interesting therapeutic properties. Betulinic acid (BeA) is a pentacyclic triterpene which has great cytotoxic activity against different cancer types. Herein, we developed a nanosized protein-based DDS of bovine serum albumin (BSA) as the drug carrier combining two compounds: doxorubicin (Dox) and the triterpene BeA using an oil-water-like micro-emulsion method. Spectrophotometric assays were performed to determine protein and drug concentrations in the DDS. The biophysical properties of these DDS were characterized using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy confirming nanoparticle (NP) formation and drug loading into the protein structure, respectively. The encapsulation efficiency was 77% for Dox and 18% for BeA. More than 50% of both drugs were released within 24 h, at pH 6.8, while less drug was released at pH 7.4 in this time period. Co-incubation viability assays of Dox and BeA alone for 24 h demonstrated synergistic cytotoxic activity in the low μM range against the non-small cell lung carcinoma (NSCLC) A549 cells. Viability assays of the BSA(Dox+BeA) DDS demonstrated a higher synergistic cytotoxic activity than the two drugs with no carrier. Moreover, confocal microscopy analysis confirmed cellular internalization of the DDS and nucleus accumulation of the Dox. We determined the mechanism of action of the BSA(Dox+BeA) DDS, confirming S-phase cell cycle arrest, DNA damage, caspase cascade activation, and downregulation of the epidermal growth factor receptor (EGFR) expression. This DDS has the potential to synergistically maximize the therapeutic effect of Dox and diminish chemoresistance induced by EGFR expression using a natural triterpene against NSCLC.

The national rate of obesity in US Hispanic/Latinos exceeds all other major ethnic subgroups and represents an important health disparity. Plant-based diet interventions that emphasize whole plant foods with minimal processing and less refined grains and sugar have shown have shown great promise in control of obesity, but there is a paucity of data translating this treatment effect to disparity populations. The objective of our study was to evaluate the efficacy and scalability of the Healthy Eating Lifestyle Program (HELP) – a hospital-based, family centered, culturally tailored, plant-based diet intervention for Hispanic/Latino pediatric obesity patients and their families. Our evaluation methods included: 1) a quasi-experimental, one group, longitudinal study to measures changes in BMI at 0, 6, and 18 weeks of follow-up, and 2) A stakeholder analysis consisting of six key informant interviews of HELP program staff. We found a significant decrease in body mass index across all adults (-0.2 kg/m² p=0.0047), that was much stronger in men. For children ages 5-12 years, there was also a significant decrease in BMI Z score from pre- to post- intervention (p=0.04). Program strengths were the cultural tailoring of the plant-based diet choices, and allowing a tiered approached that did not require adherence to strict vegetarianism. Our pilot study findings from HELP raise the possibility that incorporating plant-based diet choices into the treatment of pediatric obesity patients and their families can be an effective addition to a culturally responsive care model.

A novel chemically cross-linked hydrogel was prepared through the utilization of the nor-bornene (Nb)-methyl tetrazine (mTz) click reaction, derived from carboxymethyl cellulose (CMC) and alginate (Alg). The hydrogel was designed to generate reactive oxygen species (ROS) from NIR-dye, indocyanine green (ICG) for a combined photothermal and photodynamic ther-apy (PTT/PDT). The cross-linking of Nb and mTz moieties occurred via an inverse elec-tron-demand Diels-Alder reaction under physiological conditions avoiding the need for a cata-lyst. The resulting hydrogels exhibited viscoelastic properties (G′ ~ 492-270 Pa) and high porosi-ty. The hydrogels were found to be injectable with tunable mechanical characteristics. The ICG encapsulated hydrogels demonstrated ROS generation ability under NIR exposure. The ROS production was investigated through DPBF assays to access photodynamic effect (with NIR irra-diation at 1-2W for 5-15 min). The temperature of the ICG-loaded hydrogels was also raised up-on the NIR irradiation to eradicate tumor cells photothermally. In vitro cytocompatibility as-sessments revealed the non-toxic nature of CMC-Nb and Alg-mTz towards HEK-293 cells. Fur-thermore, the ICG-loaded hydrogels effectively inhibited the metabolic activity of Hela cells following NIR exposure. This innovative hydrogel system holds promise for applications in combined PTT and PDT.

Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated dis-ease, but exact pathomechanism remains still unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize, IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, Meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, atopic dermatitis and of healthy control dogs using a competitive canine IL-31 ELISA. Mean serum IL-31 level in dogs with SRMA (n=18) was mildly higher compared to dogs with atopic dermatitis (n=3) and MUO (n=15) and markedly higher than in healthy controls (n=10) and dogs with infectious meningoencephalitis (n=3). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value of dogs with SRMA (n=23) was quite similar to healthy controls (n=8) and did not differ significantly from dogs with MUO (n=19) and infectious meningoencephalitis (n=2). Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 im-mune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction.

Geminiviruses possess single-stranded, circular DNA genomes, and control the transcription of their late genes, including BV1 of many bipartite begomoviruses, through transcriptional activation by the early expressing AC2 protein. DNA binding by AC2 is not sequence-specific, hence the specificity of AC2 activation is thought to be conferred by plant transcription factors (TFs) recruited by AC2 in infected cells. However, the exact TFs AC2 recruits are not known for most viruses. Here we report a systematic examination of the BV1 promoter (PBV1) of mungbean yellow mosaic virus (MYMV) for conserved promoter motifs. We found that MYMV PBV1 contains three abscisic acid (ABA)-responsive elements (ABREs) within its first 70 nucleotides. Deleting these ABREs, or mutating them all via site-directed mutagenesis, abolished the capacity of PBV1 to respond to AC2-mediated transcriptional activation. Furthermore, ABRE and other related ABA-responsive elements were prevalent in more than a dozen Old World begomoviruses we inspected. Together these findings suggest that ABA-responsive TFs may be recruited by AC2 to BV1 promoters of these viruses to confer specificity to AC2 activation. These observations are expected to guide the search for the actual TF(s), furthering our understanding of the mechanism of AC2 action.

Regenerated silk (RS) is a protein-based “biopolymer” that enables the design of new materials; here, we called “bionic” the process of regenerated silk production by a fermentation-assisted method. Based on yeast’s fermentation, here we produced a living hybrid composite made of regenerated silk nanofibrils and a single-cell fungi, the Saccharomyces cerevisiae yeast extract, by fermentation of such microorganisms at room temperature in a dissolution bath of silkworm silk fibers. The fermentation-based processing enhances the beta-sheet content of the RS, corresponding to a reduction in water permeability and CO₂ diffusion through RS/yeast thin films enabling the fabrication of a mechanically robust film that enhances food storage durability. Finally, a transfer print method, which consists of transferring RS and RS/yeast film layers onto a self-adherent paraffin substrate, was used for the realization of heat-responsive wrinkles by exploiting the high thermal expansion of the paraffin substrate that regulates the applied strain, resulting in a switchable coating morphology from the wrinkle-free state to a wrinkled state if the food temperature overcomes a designed threshold. We envision that such efficient and smart coatings can be applied for the realization of smart packaging that, through such a temperature-sensing mechanism, can be used to control food storage conditions.

Novel pH responsive semi-interpenetrating polymer hydrogels based on tamarind gum-co-poly(acrylamidoglycolic acid) (TMGA) polymers have been synthesized using simple free radical polymerization in the presence of bis[2-(methacryloyloxy)ethyl] phosphate as a crosslinker and potassium persulfate as a initiator. In addition, these hydrogels have been used as templates for green synthesis of silver nanoparticles (13.4±3.6 nm in diameter, TMGA-Ag) by using leaf extract of Teminalia bellirica as reducing agent. Swelling kinetics and equilibrium swelling behavior of the TMGA hydrogels have been investigated in various pH environment the maxium % equilibrium swelling behavior observed i.e., 2882±1.2. The synthesized hydrogels and silver nanocomposites have been characterized by the UV, FTIR, XRD, SEM and TEM. TMGA and TMGA-Ag hydrogels have been investigated to study the characteristics of drug delivery and antimicrobial study. Doxorubicin hydrochloride, a chemotherapeutic agent successfully encapsulated with maximum encapulstaion efficiency i.e., 69.20±1.2 and performed in vitro release studies in pH physiological and gastric environment at 37 ℃. The drug release behavior is examined with kinetic models such as zero order, first order, Higuchi, Hixson Crowell, Korsmeyer-Peppas. These release data was the best fitted with the Korsemeyer-Peppas transport mechanism with n=0.91. Treatment effect on HCT116 Cell, human colon cancer cells were assessed with cell viability and cell cycle analysis. Antimicrobial activity of TMGA-Ag hydrogels is studied against to Staphylococcus aureus and Klebsiella pneumonia. Finally, the results demonstrate that TMGA and TMGA-Ag are promising candidates for anti-cancer drug delivery and inactivation of pathogenic bacteria, respectively.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

In this paper, we introduce a specialized, fully automated experimental arrangement designed for assessing the effectiveness of augmented and virtual reality technologies in healthcare setting and explore its design principles focusing on depth sensor characterization. The main goal of this project is to establish a robust benchtop platform for the quantitative evaluation of extended reality technologies in a controlled environment, emphasizing the practical assessment of augmented reality head-mounted devices. We outline a design concept and considerations for an experimental configuration aimed at creating a realistic testing environment. This apparatus comprises an observation platform mounted on a three-degree-of-freedom motorized system and a test phantom stage. Focusing on real-case scenarios, we utilized a range of sensors, including readily available range-sensing cameras and commercial augmented reality headsets, such as the Intel RealSense L515 LiDAR camera, mounted on the motion control system. The setup enabled automated data collection and facilitates controlled assessments and validation of various facets of augmented reality technologies, including object, hand, and head tracking, as well as static and dynamic image registration. This paper describes the system architecture, the process of automated data collection, and presents several evaluation studies conducted with this setup, providing insights into the quality and temporal noise associated with static or moving objects or observers in augmented reality applications.

To conduct high-precision and high-resolution numerical simulation of complex flow structures in turbomachinery, a high-order finite volume weighted essentially non-oscillatory (WENO) scheme for the large eddy simulation (LES) is improved and embedded into the three-dimensional viscous unsteady CFD solver NUAA-Turbo. Firstly, the spectral characteristics and unsteady convergence of the improved WENO scheme are studied. Compared with the classical WENO scheme, the improved WENO scheme has better dissipation and dispersion characteristics and faster convergence speed. Then, the coefficient CW of the Wall-Adapting Local Eddy-viscosity (WALE) model is calibrated by decaying homogeneous isotropic turbulence (DHIT) test case. Finally, the scheme is applied to conduct high-precision LES calculations of turbulent boundary layer flow, supersonic compression corner flow, and low-pressure turbine cascade separation flow. The numerical simulation results show that this WENO scheme has excellent shock wave capture ability and turbulence resolution and can capture more flow field details with less mesh size, greatly reducing the computational cost and laying a foundation for large-scale engineering application of LES.

To secure logic circuits against the illegal copying the insertion of the so-called key bit inputs using XOR/XNOR gates has been proposed in . The inserted gates modify (lock) the behavior of the original circuit and only the correct choice of the secret key bits guarantees the equivalent behaviour of the locked circuit to the original circuit. To break this kind of security, i.e. to find the secret key bits, there was a SAT solver based attack proposed in . The aim of this work is to experimentally verify this attack on several locked circuits with various number of primary inputs and outputs and with various number of gates. Except for the random placement of the key gates we evaluate also the positioning with chaining elimination. The obtained and presented results show that we were able to unlock 10 of 11 circuits within few minutes on a common PC.

Intermetallic compounds are increasingly being expected to utilize in tribological environments, but to date the works are hindered by insufficient ductility at low and medium temperature. This paper presents a novel multiphase intermetallic alloy with the chemical composition of Mo-40Ni-13Si (at.%). Microstructure characterization reveals that a certain amount of ductile Mo phases formed during the solidification process of ternary Mo-Ni-Si alloy melt, which is undoubtedly beneficial to the ductility improvement of intermetallic alloy. Tribological properties of the designed alloy, including wear resistance, friction coefficient and metallic tribological compatibility, were evaluated under dry sliding wear test conditions at room temperature. Results suggested that the multiphase alloy possesses an excellent property for room-temperature wear applications, which is attributed to the unique microstructural features and thereby good combination in hardness and ductility. The corresponding wear mechanism is also reported by observing the worn surface, subsurface and wear debris of alloy, which to be found is soft abrasive wear.

With the integrated development of the Internet, wireless sensor technology, cloud computing, and mobile Internet, there has been a lot of attention given to research about and applications of the Internet of Things. A Wireless Sensor Network (WSN) is one of the important information technologies in the Internet of Things; it integrates multi-technology to detect and gather information in a network environment by mutual cooperation, using a variety of methods to process and analyze data, implement awareness, and perform tests. This paper mainly researches the localization algorithm of sensor nodes in a wireless sensor network. Firstly, a multi-granularity region partition is proposed to divide the location region. In the range-based method, the RSSI (Received Signal Strength indicator, RSSI) is used to estimate distance. The optimal RSSI value is computed by the Gaussian fitting method. Furthermore, a Voronoi diagram is characterized by the use of dividing region. Rach anchor node is regarded as the center of each region; the whole position region is divided into several regions and the sub-region of neighboring nodes is combined into triangles while the unknown node is locked in the ultimate area. Secondly, the multi-granularity regional division and Lagrange multiplier method are used to calculate the final coordinates. Because nodes are influenced by many factors in the practical application, two kinds of positioning methods are designed: the unknown node is in the positioning unit or not. When the unknown node is on the side of the positioning unit, we use the method of vector similarity. Moreover, we use the centroid algorithm to calculate the ultimate coordinates of unknown node. When the unknown node is not on the side of the positioning unit, we establish a Lagrange equation containing the constraint condition to calculate the first coordinates. Furthermore, we use the Taylor expansion formula to correct the coordinates of the unknown node. In addition, this localization method has been validated by establishing the real environment.

The electroencephalogram (EEG) is a record of brain activity. Brain Computer Interface (BCI) technology formed by the EEG signal has become one of the hotspots at present. How to extract the feature signal of EEG is the most basic research of BCI technology. In this paper, A new method of recognizing fatigue, conscious, concentrated state of human brain is proposed by the combination of discrete wavelet transform and the neural network based on EEG signal. First of all, the law signal is preprocessed by the wavelet denoising method because the law EEG signal contains a large number of high frequency noise, which is decomposed into multi-layer high frequency signal and low frequency signal. thus, δ wave, θ wave, α wave, β wave are obtained by the wavelet transform. And then, frequency band energy of the different wave is regards as the feature signal of EEG. In the experiment, the feature signal is classified by radial basic function (RBF) and annealed chaotic competitive learning network (ACCLN). RBF and ACCLN networks are trained with 500 sets of sample data and are tested by 100 sets of samples in different mental states. The experimental results show that the average accuracy of RBF network under three conditions are 88.75%, 88.25%, 88.5%, respectively, and the correct rate of ACCLN network is 97%, 98%, 98%, respectively.

Early discharge after childbirth has led to a rise in neonatal readmission, becoming a major concern in recent decades. Our research aimed to identify the risk factors and incidence of neonatal readmission, as well as explore preventive measures. Our study at the Clinical Hospital of Pediatrics in Ploiești, Romania included 108 neonates admitted during the neonatal period. This accounted for 2.06% of all admissions (5226). The most prevalent cases were malnutrition (25%), fever (20.3%) and bronchiolitis (17.5%). Diarrhea and infectious gastroenteritis were also observed (14.8%), along with acute rhinoconjunctivitis (9.2%) and late onset sepsis (3.7%). No deaths were recorded. The most significant characteristics identified were number of children (p&lt;0.001) and age at maternity discharge (p&lt;0.001). By following the prevention rules, malnutrition, feeding errors, and infections can be avoided. This includes practicing proper hand hygiene for both mothers and medical staff, as well as educating and demonstrating to mothers the benefits of breastfeeding. In addition, all newborns discharged from the maternity ward should benefit from follow-up at 7-10 days of life. Our results confirm the effectiveness of a multidisciplinary team and endorse promoting breastfeeding. Implementing quality control measures and regularly evaluating the surveillance program will help improve its effectiveness.

Wearable technology has been proposed as a potential tool to change the way of human life, such as the smart bracelet and the Google Glass. In the wearable technology, the inertial sensor has great significance in tracking the object movements. The paper focused on detecting the movements of user’s finger based on the inertial sensor to give the control signals. Firstly, the attitude matrix, which represented the transformation relation of carrier coordinate system and the navigation coordinate system, was obtained. Secondly, the attitude matrix was expressed based on the quaternions. Thirdly, the finger gesture was processed by the attitude matrix to get the attitude angle. Finally, the robot was controlled by attitude angle to make the moving action. The experimental results showed the detection of the finger movement is effective.

Two interesting compounds such as quaternary ammonium lignin(QAL) and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester (P507) were synthesized as ionic liquids(QP-ILs) for the extraction of metal ions. The extraction behavior of Co(II) and Ni(II) from chloride solution was compared between QP-ILs and P507. The results showed that the extraction rates of Co(II) and Ni(II) in the two solutions varied with the extraction conditions, but QP-ILs has stronger extractability for cobalt than P507, while Ni is on the contrary. Under the same conditions, the Co/Ni separation performance(βCo/Ni) in QP-ILs is superior to that in p507. At pH4.0, 55℃, concentration of 20%, extraction time of 10 minutes, the βCo/Ni of QP-ILs reached to 2703, while that of P507 was only 164. In conclusion, QP-ILs was more efficient than P507 for separating Co from mixed solutions.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

In this paper, we study the semilinear pseudo-parabolic equations $\displaystyle u_{t} - \triangle_{\mathbb{B}}u - \triangle_{\mathbb{B}}u_{t} = \left|u\right|^{p-1}u$ on a manifold with conical singularity, where $\triangle _{\mathbb{B}}$ is Fuchsian type Laplace operator investigated with totally characteristic degeneracy on the boundary $x_{1} = 0$. Firstly, we discuss the invariant sets and the vacuum isolating behavior of solutions with the help of a family of potential wells. Then, we derive a threshold result of existence and nonexistence of global weak solution: for the low initial energy $J(u_{0})<d$, the solution is global in time with $I(u_{0}) >0$ or $\displaystyle\Vert \nabla_{\mathbb{B}}u_{0}\Vert_{L_{2}^{\frac{n}{2}}(\mathbb{B})} = 0$ and blows up in finite time with $I(u_{0}) < 0$; for the critical initial energy $J(u_{0}) = d$, the solution is global in time with $I(u_{0}) \geq0$ and blows up in finite time with $I(u_{0}) < 0$. The decay estimate of the energy functional for the global solution and the estimates of the lifespan of local solution are also given.

Multimodal remote sensing data classification can enhance the model’s ability to distinguish land features through multimodal data fusion. In this context, how to help models understand the relationship between multimodal data and target tasks is the focus of researchers. Inspired by human feedback learning mechanisms, causal reasoning mechanisms, and knowledge induction mechanisms, this paper integrates causal learning, reinforcement learning, and meta learning into a unified remote sensing data classification framework and proposed the causal meta-reinforcement learning (CMRL). First, based on feedback learning mechanisms, we have overcome the limitations of traditional implicit optimization of fusion features and customized a reinforcement learning environment for multimodal remote sensing data classification tasks. Through feedback interactive learning between agents and the environment, we help them understand the complex relationships between multimodal data and labels, thereby achieving full mining of multimodal complementary information. Second, based on the causal inference mechanism we designed causal distribution prediction action, classification reward, and causal intervention reward, capturing pure causal factors in multimodal data and cutting off false statistical associations between non-causal factors and class labels. Finally, based on the knowledge induction mechanism, we designed a bi-layer optimization mechanism based on meta-learning. By constructing a meta training task and meta validation task simulation model in the generalization scenario of unseen data, we helped the model induce cross-task shared knowledge, thereby improving its generalization ability for unseen multimodal data. The experimental results on multiple sets of multimodal datasets show that the proposed method achieved state-of-the-art performance in multimodal remote sensing data classification tasks.

Moso bamboo is famous for fast growing and biomass accumulation, as well as high annual output for timber and bamboo shoots. These high outputs require high nutrient inputs to maintain and improve stand productivity. Soil nitrogen (N), phosphorus (P) and potassium (K) are important micronutrients for plant growth and productivity. Due to high variability of soils, analysing spatial patterns of soil N, P and K stocks is necessary for scientific nutrient management in Moso bamboo forests. In this study, soils were sampled from 138 locations across Yong’an City and ordinary kriging was applied for spatial interpolation of soil N, P and K stocks. Soil N stock showed a strong spatial dependence while soil N and P stocks presented a moderate spatial dependence, indicating soil N was mainly controlled by intrinsic factors while soil N and P stocks were controlled by both intrinsic and extrinsic factors. Different spatial patterns were observed for soil N, P and K stocks across the whole study area, indicating that fertilizations with different ratios of N:P:K should be applied for different sites to maintain and improve stand productivity. The total soil N, P and K stocks within 0-60 cm were 0.624, 0.020 and 0.583 Tg, respectively.

With the increasing concern of environment, the energy-efficiency scheduling of manufacturing industry is becoming urgent and popular. In turning processes, both spindle speed and processing time can affect the final energy consumption and thus the spindle speed and scheduling scheme need to be optimized simultaneously. Since the turning workshop can be regarded as the flexible flow shop, this paper formulates a mixed integer linear programming model for energy-efficient scheduling of flexible flow shop. Accordingly, a new decoding method is developed by considering of the optimization of spindle speed and scheduling scheme simultaneously, and an estimation of distribution algorithm adopting the new decoding method is proposed to solve large-size problems. The parameters of this algorithm are determined by statistical technique with a simplified practical case. In order to validate the proposed method, a case from practical factories is studied, in which the makespan can be shortened by 25.22%, and the consumed energy can be saved by 5.48%. These results demonstrate the effectiveness of the proposed mathematical model and algorithm.

Lignocellulosic biomass, an abundant and renewable resource, serves as a crucial raw material for the production of biofuels, biochemicals, and various value-added products. This paper aims to develop and optimize a mild alkaline treatment of sawdust assisted by ultrasound, along with enzymatic hydrolysis of the pretreated material. The sonochemical pretreatment with alkali emerged as the optimal approach to enhance the susceptibility of cellulose to subsequent enzymatic hydrolysis, thereby increasing the yield of reducing sugars. A comparative study was performed using various ultrasonic applicators (horn and bath) and conventional assisted alkaline pretreatment. The ultrasonic assisted pretreatment revealed a higher delignification as 68% (horn) and 57% (bath) comparing with conventional pretreatment. Processes were optimized using a statistical analysis based on a 23 factorial design. The ratio between sawdust and alkanine solution (RSL = 0.5–1.5 g/100 mL), US amplitude (A = 20–60%), and working temperature (t = 30–50 °C) were selected as process factors. The optimal operating conditions to maximize the reducing sugar yield (138.15 mg GE /gsubstrate) were found as following: solid/liquid ratio RSL,opt = 1.25 g/100 mL, US amplitude Aopt = 60%, and and pretreatment temperature topt = 50 °C. The overall outcomes clearly confirmed the intensification of delignification by ultrasound assisted alkaline pretreatment

At 12:28 UTC (8:28 PM, local time) on 15 January 2023, a shallow, moderate earthquake with a magnitude (Mw) of 4.7 and a depth of one (1) kilometer shook the northern part of Leyte Island in the central part of the Philippines. The ground shaking was felt at PHIVOLCS Earthquake Intensity Scale (PEIS) VI, (very strong) equivalent to Modified Mercalli Intensity (MMI) VI in areas along the strike of the Leyte segment of the Philippine Fault. Even though this earthquake is classified as moderate in size, significant geologic, structural, and socio-economic impacts were documented. Most of the earthquake impacts that include surface rupture, liquefaction, and mass movements are limited near the epicentral area. The earthquake produced an 8-km-long surface rupture, the first documented rupture generated by a magnitude &lt;6 along the Philippine Fault, and is unusual in other surface rupturing earthquakes worldwide. It injured 18 persons and damaged 434 residential buildings and 26 public infrastructures which amounts to about 500 thousand US dollars. Structural damages were caused by surface rupture and/or poor engineering construction practices. Analysis of the seismic waveform and recorded peak ground acceleration (PGA) suggests that the subsurface geology influenced the ground motion amplification in an area near the epicenter. Based on the hypocenter, focal mechanism solution, aftershock distribution, and actual field observation, the causative fault for this event is the northern end of the Philippine Fault – Leyte segment. Moderate in size, this earthquake emphasizes the need and importance of documenting moderate-sized earthquakes as a tool and guide for medium and long-term earthquake risk assessment and resiliency.

Background: The bacterium Capnocytophaga spp. is a part of the oral microbiome of dogs, which has zoonotic potential. This study aimed to assess factors that influence the prevalence of Capnocytophaga cynodegmi and Capnocytophaga canimorsus in Wrocaw’s dog population. Methods: Molecular detection (PCR) involved 105 swabs, examining parameters such as oral cavity condition, underlying health issues, recent antibiotics, age, medications, material collection, and dog chews. Results: The study highlighted significant associations between the presence of Capnocytophaga cynodegmi and oral cavity condition, material collection method, and use of dog’s chews. Conclusions: Correlations obtained in this study between the oral health of Wroclaw's dog population and the presence of Capnocytophaga cynodegmi suggest its significance in the oral microbiome of dogs. Limitations, including the small sample size, highlight the need for more research to comprehensively understand additional factors that affect the prevalence of Capnocytophaga spp. in dogs

A simple design of an ultrathin six-band polarization-insensitive terahertz perfect metamaterial absorber (PMMA) composed of a metal cross-cave-patch resonator (CCPR) placed over a ground plane was proposed and investigated numerically. The numerical simulation results demonstrate that the average absorption peaks are up to 95% at six resonance frequencies with high quality-factors (>65). In addition, the absorption properties can be kept stability for both normal incident transverse magnetic (TM) and transverse electric (TE) waves. The physical mechanism behind the observed high level absorption is illustrated by the electric and power loss density distributions. The different absorption mainly originates from the higher order multipolar and multipolar plasmon resonance of the structure, which are sharp different to the most previous studies of the PMMAs. Furthermore, the resonance absorption of the PMMA can be tunable by varying the geometric parameters of the unit cell.

A simple design of an ultrathin six-band polarization-insensitive terahertz perfect metamaterial absorber (PMMA) composed of a metal cross-cave-patch resonator (CCPR) placed over a ground plane was proposed and investigated numerically. The numerical simulation results demonstrate that the average absorption peaks are up to 95% at six resonance frequencies with high quality-factors (>65). In addition, the absorption properties can be kept stability for both normal incident transverse magnetic (TM) and transverse electric (TE) waves. The physical mechanism behind the observed high level absorption is illustrated by the electric and power loss density distributions. The different absorption mainly originates from the higher order multipolar and multipolar plasmon resonance of the structure, which are sharp different to the most previous studies of the PMMAs. Furthermore, the resonance absorption of the PMMA can be tunable by varying the geometric parameters of the unit cell.