Search Results (57)

Defects in lysosomal cholesterol handling provoke fatal disorders presenting neurovisceral symptoms with variable onset and life spans. A prime example is Niemann–Pick type C disease (NPCD), where cholesterol export from the endosomal–lysosomal system is impaired due to variants of either NPC intracellular cholesterol transporter 1 (NPC1) or NPC intracellular cholesterol transporter 2 (NPC2). Therapeutic options for NPCD are limited to palliative care and disease-modifying drugs, and there is a need for new treatments. Here, we explored bromodomain and extra-terminal domain (BET) proteins as new drug targets for NPCD using patient-derived skin fibroblasts. Treatment with JQ1, a prototype BET protein inhibitor, raised the level of NPC1 protein, diminished lysosomal expansion and cholesterol accumulation, and induced extracellular release of lysosomal components in a dose-, time-, and patient-dependent manner. Lastly, JQ1 enhanced and reduced cholesterol accumulation induced by pharmacologic inhibition of NPC1 and of histone deacetylase (HDAC) activity, respectively. Taken together, bromodomain proteins should be further explored as therapeutic drug targets for lysosomal diseases like NPCD, and as new components regulating lysosomal function and cholesterol metabolism. Full article

In this research, we propose a bagworm-inspired robot that can acquire its exterior by incorporating various objects from the surrounding environment into its skin. This study was inspired by the bagworm, the larva of the giant bagworm moth, which wraps itself around straw and other materials to use as a nest. When the robot is active outdoors, it is surrounded by natural materials such as sand, fallen leaves, and pieces of wood, and can change its skin by attaching or detaching these materials as needed. In the previous study, the authors developed a camouflage robot that assimilates with the outside world by incorporating natural environmental sand. In this study, by using a water-soluble adhesive as the adhesive material, it is possible to take in a larger number of external substances than before. We also conducted experiments with natural materials, including leaves and pebbles, and confirmed that the robot could pick them up. We expect that by developing these functions, robots will not only have camouflage capabilities but also the ability to reinforce their own skin like bagworms. Full article

Chronic pruritus (CP), attention-deficit/hyperactivity disorder (ADHD), and skin picking disorder (SPD) are medical conditions that involve both somatic and psychosocial dimensions, posing unique challenges in clinical management. While CP and SPD are often observed together, the link between ADHD and these conditions is less recognized. This conceptual work describes three women who suffered from a complex interplay of CP, ADHD, and SPD treated at our specialized bi-disciplinary psychodermatological pruritus clinic. Based on our clinical observation and a narrative review of the literature, we assume a bidirectional, triangular relationship between CP, ADHD, and SPD. To support this assumption, we propose two hypotheses: (1) a neurodevelopmental hypothesis, emphasizing that an underlying neurodevelopmental disorder, in this case, ADHD, might present with symptoms like dysfunction of sensory processing, impulsivity, and attention deficits as shared features that reinforce CP and SPD, and (2) a neuroinflammatory hypothesis, suggesting that similar neuroinflammatory signatures promote the co-occurrence of CP, ADHD, and SPD. In addition, we provide specific suggestions derived from our clinical experience on how to manage patients with this complex combination of conditions. Elucidating the interplay between CP, ADHD, and SPD might help develop personalized treatment strategies and improve outcomes. Full article

Niemann–Pick type C (NPC) is a lysosomal storage disorder (LSD) caused by pathogenic variants in either the NPC1 or NPC2 genes, which encode proteins involved in the lysosomal export of unesterified cholesterol. In patients of Western European descent, the p.Ile1061Thr variant in NPC1 is especially prevalent. However, mounting evidence has positioned p.Ala1035Val as the most common variant in Portugal and the second most prevalent variant worldwide. By analyzing 10 Portuguese NPC patients homozygous for p.Ala1035Val, we found an SNP in cis on position 858 (p.Ile858Val), which we hypothesize could have a disease-modifying effect. To address this query, we created variant-specific in vitro models of NPC by stably transducing NPC1^−/− ARPE-19 cells with constructs encoding different fluorescently-tagged variants of NPC1, which we used, alongside patient-derived skin fibroblasts, to investigate lysosomal positioning and the trafficking routes elicited by p.Ile1061Thr and p.Ala1035Val (with and without the p.Ile858Val SNP in cis). Our results corroborate the previously described decrease in p.Ile1061Thr-NPC1 trafficking to the lysosome and suggest a similar, if not worse, scenario for the p.Ala1035Val variant, especially when in cis with p.Ile858Val. This is the first reported functional study addressing the impact of the p.Ala1035Val variant at the cellular level, paving the way for novel therapeutic options. Full article

Falling damage is the most common form of damage sustained by kiwifruit during the process of picking and post-processing, and it is difficult to conduct a quantitative analysis of this phenomenon through traditional experimental methods. In order to deeply understand the sensitivity of kiwifruit to falling collision damage, the finite element numerical simulation method was used to evaluate and predict the sensitivity of kiwifruit to falling collision damage during harvesting. First, we obtained the appearance characteristics of kiwifruit through reverse engineering technology and determined the geometric and mechanical property parameters of kiwifruit through physical mechanics experiments. Then, according to the characteristics of fruit tissue structure, a multiscale finite element model, including the skin, pulp, and core, was constructed to simulate the effects of different falling heights, collision angles, and contact surface materials on fruit damage, and the accuracy of the model was verified through falling experiments. Finally, based on the simulation results, the Box–Behnken design was employed within the response surface methodology to establish a sensitivity prediction model for the drop damage sensitivity of kiwifruit across different contact materials. The results showed that the maximum relative error between the speed change obtained using finite element simulation and the speed obtained by the high-speed camera was 5.19%. The model showed high rationality in energy distribution, with the maximum value of hourglass energy not exceeding 0.08% of the internal energy. On the contact surface material with a large elastic modulus, a higher falling height and larger collision angle will significantly increase the risk of fruit bruise. When the contact surface material was a steel plate, the falling height was 1 m, and the collision angle was 90°; the maximum bruise sensitivity of kiwifruit reached 6716.07 mm³ J⁻¹. However, when the contact surface material was neoprene, the falling height was 0.25 m, and the collision angle was 0°, the damage sensitivity was the lowest, at 1570.59 mm³ J⁻¹. The multiscale finite element model of kiwifruit falling collision constructed in this study can accurately predict the damage of kiwifruit during falling collision and provide an effective tool for the quantitative analysis of kiwifruit falling collision damage. At the same time, this study can also provide guidance for the design and optimization of the loss reduction method of the harvesting mechanism, which has important theoretical significance and practical value. Full article

For thousands of years, pearl and nacre powders have been important traditional Chinese medicines known for their skin whitening effects. To prepare the enzymatic hydrolysates of Hyriopsis cumingii nacre powder (NP-HCH), complex enzymatic hydrolysis by pineapple protease and of neutral protease was carried out after the powder was pre-treated with a high-temperature and high-pressure method. The peptides were identified using LC-MS/MS and picked out through molecular docking and molecular dynamics simulations. Subsequently, the tyrosinase inhibitory and antioxidant properties of novel tyrosinase inhibitory peptides were investigated in vitro. In addition, the enzymatic activity of tyrosinase in B16F10 cells as well as melanin content and antioxidant enzyme levels were also examined. The results showed that a tyosinase inhibitory peptide (Tyr-Pro-Asn-Pro-Tyr, YPNPY) with an efficient IC₅₀ value of 0.545 ± 0.028 mM was identified. The in vitro interaction results showed that YPNPY is a reversible competitive inhibitor of tyrosinase, suggesting that it binds to the free enzyme. The B16F10 cell whitening test revealed that YPNPY can reduce the melanin content of B16F10 cells by directly inhibiting the activity of intracellular tyrosinase. Additionally, it indirectly affects melanin production by acting as an antioxidant. These results suggest that YPNPY could be widely used as a tyrosinase inhibitor in whitening foods and drugs. Full article

The mechanized harvesting level of potatoes in the arid areas of Northwest China is low and mainly relies on simple machinery to dig the soil surface, and then people manually pick up and bag the potatoes. This harvesting method has the problems of a high labor intensity, low operation efficiency, and high labor cost. Based on this, a wheeled-chassis potato combine harvester with integrated bagging and ton bag-lifting systems was developed, which could complete potato digging, potato–soil separation, potato–film separation, automatic bagging, and field ton bag lifting in one go. Firstly, based on the agronomic requirements and unique terrain characteristics of potato planting in this area, the structural design of the whole machine was completed with SOLIDORKS 2019 3D software. Secondly, the dynamic model was established for a numerical analysis, and the core parameters of key components were determined. The field experiments showed that the potato loss rate was 2.1%, the potato damage rate was 1.7%, the skin breaking rate was 2.5%, the impurity content was 1.9%, and the productivity was 0.15~0.23 hm²/h. The above field test indexes met the requirements of national and industrial standards. Full article

Berries are nutritious and valuable, but their thin skin, soft flesh, and fragility make harvesting and picking challenging. Manual and traditional mechanical harvesting methods are commonly used, but they are costly in labor and can damage the fruit. To overcome these challenges, it may be worth exploring alternative harvesting methods. Using berry fruit-picking robots with perception technology is a viable option to improve the efficiency of berry harvesting. This review presents an overview of the mechanisms of berry fruit-picking robots, encompassing their underlying principles, the mechanics of picking and grasping, and an examination of their structural design. The importance of perception technology during the picking process is highlighted. Then, several perception techniques commonly used by berry fruit-picking robots are described, including visual perception, tactile perception, distance measurement, and switching sensors. The methods of these four perceptual techniques used by berry-picking robots are described, and their advantages and disadvantages are analyzed. In addition, the technical characteristics of perception technologies in practical applications are analyzed and summarized, and several advanced applications of berry fruit-picking robots are presented. Finally, the challenges that perception technologies need to overcome and the prospects for overcoming these challenges are discussed. Full article

Due to a shortage of labor, the harvesting of fruits and vegetables faces significant challenges. Soft robotic hands, adaptable to variable environments due to their high-curvature bending and twisting, have garnered widespread attention and usage. However, their application in Sichuan pepper picking remains largely unexplored. Therefore, this study proposes a picking soft robotic hand composed of a rigid skeleton and flexible skin for pepper harvesting. Through analyzing the characteristics of peppers, the structure of the robotic hand is determined. Inflatable airbags are employed to drive finger bending, utilizing a rotating–twisting method for Sichuan pepper picking. Structural parameters influencing the bending angle of the airbags were determined through theoretical analysis and validated via simulation. Optimal parameter combinations for the airbags were obtained through response surface experiments to establish the robotic hand model. To assess the feasibility of the robotic hand’s movement, dynamic simulations were conducted using R D (RecurDyn V9R2) software. Subsequently, a discrete element model of Sichuan pepper clusters was established and coupled with the simulation of the Sichuan pepper picking process. The results indicate that the robotic hand does not cause damage to the Sichuan peppers during picking. Finally, field tests were conducted in pepper orchards to validate the success rate of the robotic hand in picking, yielding an 85% success rate and a 0.3% damage rate. Full article

Different lipid phase ratios (12, 14, and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad-spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro: spreadability, viscosity, pH, occlusion factor, BMTZ release, and sun protection factor (SPF). Sensory attributes were assessed by panelists in three different phases: before/during pick-up, rub-in, and after application. Raising the lipid phase ratio led to an increase in viscosity (from 8017 ± 143 cPs to 16,444 ± 770 cPs) and to a corresponding decrease in spreadability (from 9.35 ± 0.21 cm to 7.50 ± 0.10 cm), while the incorporation of BMTZ-loaded NLC determined a decrease in the occlusion factor (from 47.75 ± 1.16 to 25.91 ± 1.57) and an increase in SPF (from 6% for formulations containing 12% lipid phase to 15% for formulations containing 16% lipid phase). No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by the lipid phase ratio. These results suggest that the lipid phase ratio and BMTZ incorporation into NLC could contribute to determining the technological and sensory properties of O/W emulsions. Full article

To address problems encountered in current potato harvesting machines, such as potato damage, poor adaptability, and low operational efficiency, a new towed potato picking and bagging machine (4UJ-180A) equipped with a soil-digging axis, flexible conveying device, and hydraulic control system was developed. The digging mechanism of the harvester can reduce soil blockage and minimize damage to potato skins. The rubber biomimetic finger can maintain stable transportation of potatoes and minimize collisions. The hydraulic control system, the buffering components, and the bagging device work together to flexibly and continuously collect potatoes, reducing skin damage during the harvesting process. Based on the structure of the whole machine, the harvesting process, and the working principle, the soil picking, lifting buffer, and potato collection process were analyzed. Theoretical calculations were used to determine the structure and operational parameters of the potato picking, lifting buffering, and bagging segments. An experiment utilizing the orthogonal method was conducted. The experiment consisted of three factors and three levels, with the test indicators being the potato skin damage rate, potato injury rate, loss rate, and impurity rate. The factors considered in the experiment were the forward speed, conveyor speed, and soil-digging shaft speed. Field experiments demonstrate that at a forward speed of 1 m/s, soil digging shaft speed of 35 rpm, and conveyor speed of 28 rpm, the rate of potato skin damage is 2.8%, the potato injury rate is 1.3%, the loss rate is 0.4%, and the impurity rate is 0.7%. These experiments verify that all indicators adhere to national industry standards, providing a valuable reference for equipment research, development, optimization, and improvement. Full article

Breastfeeding exclusivity and duration rates are lower after caesarean birth, yet the factors contributing to these are not well understood. This mixed-methods study used an anonymous online questionnaire to examine the facilitators and barriers to establishing breastfeeding as identified by Australian women after a caesarean birth. Quantitative data were reported using descriptive statistics, and multivariable models were used to determine the factors associated with breastfeeding outcomes including the timing of breastfeeding initiation, birth experience, and commercial infant formula use. Qualitative data were analysed using an inductive thematic analysis. Data were obtained for N = 961 women, of which <50% reported skin-to-skin contact during breastfeeding initiation. The barriers to breastfeeding included aspects of clinical care and reduced mobility, while unrushed care, partner support, and physical help with picking up the baby were helpful. Following a non-elective caesarean birth, women had half the odds of early breastfeeding initiation (OR = 0.50; 95% CI: 0.36, 0.68; p ≤ 0.001) and 10 times the odds to report a negative birth experience (OR = 10.2; 95% CI: 6.88, 15.43; p < 0.001). Commercial milk formula use was higher in primiparous women (OR = 2.16; 95% CI: 1.60, 2.91; p < 0.001) and in those that birthed in a private hospital (OR = 1.67; 95% CI: 1.25, 2.32; p = 0.001). Pain and reduced mobility, as well as conflicting and rushed care, negatively impacted breastfeeding after a caesarean birth, while delayed breastfeeding initiation, higher pain ratings, and negative birth experiences were more common for women that birthed by non-elective caesarean. This study adds valuable insights into the physical, emotional, and clinical care needs of women in establishing breastfeeding after a surgical birth. Clinical staffing and care should be modified to include full access to partner support to meet the specific needs of breastfeeding women after a caesarean birth. Full article

The human body is a source of multiple types of energy, such as mechanical, thermal and biochemical, which can be scavenged through appropriate technological means. Mechanical vibrations originating from contraction and expansion of the radial artery represent a reliable source of displacement to be picked up and exploited by a harvester. The continuous monitoring of physiological biomarkers is an essential part of the timely and accurate diagnosis of a disease with subsequent medical treatment, and wearable biosensors are increasingly utilized for biomedical data acquisition of important biomarkers. However, they rely on batteries and their replacement introduces a discontinuity in measured signals, which could be critical for the patients and also causes discomfort. In the present work, the research into a novel 3D-printed wearable energy harvesting platform for scavenging energy from arterial pulsations via a piezoelectric material is described. An elastic thermoplastic polyurethane (TPU) film, which forms an air chamber between the skin and the piezoelectric disc electrode, was introduced to provide better adsorption to the skin, prevent damage to the piezoelectric disc and electrically isolate components in the platform from the human body. Computational fluid dynamics in the framework of COMSOL Multiphysics 6.1 software was employed to perform a series of coupled time-varying simulations of the interaction among a number of associated physical phenomena. The mathematical model of the harvester was investigated computationally, and quantification of the output energy and power parameters was used for comparisons. A prototype wearable platform enclosure was designed and manufactured using fused filament fabrication (FFF). The influence of the piezoelectric disc material and its diameter on the electrical output were studied and various geometrical parameters of the enclosure and the TPU film were optimized based on theoretical and empirical data. Physiological data, such as interdependency between the harvester skin fit and voltage output, were obtained. Full article

Congenital dermal melanocytosis (DM) represents a common birthmark mainly found in children of Asian and darker skin phototype descent, clinically characterized by an oval blue-grey macule or macules, commonly located on the lumbosacral area. In rare DM cases, when presenting with diffuse macules persisting during the first years of life, it could represent a cutaneous feature of mucopolysaccharidoses (MPS). Extensive congenital DM is actually associated with Hurler syndrome (MPS type I) and Hunter syndrome (MPS type II), although several reports also described this association with MPS type VI and other lysosomal storage disorders (LySD), including GM1 gangliosidosis, mucolipidosis, Sandhoff disease, and Niemann–Pick disease. Here, we present the case of a two-year-old boy presenting with extensive dermal melanocytosis, generalized hypertrichosis, and chronic itch, harboring a heterozygous variant of uncertain significance, NM_152419.3: c.493C>T (p.Pro165Ser), in the exon 4 of HGSNAT gene, whose mutations are classically associated with MPS IIIC, also known as Sanfilippo syndrome. This is the first report that highlights the association between extensive congenital DM and MPS type IIIC, as well as a pathogenetic link between heterozygous LySD carrier status and congenital DM. We speculate that some cases of extensive congenital DM could be related to heterozygous LySD carriers, as a manifestation of a mild clinical phenotype. Full article

Communicating under extreme noise conditions remains challenging in spite of higher-order noise-canceling microphones, throat microphones, and signal processing. Both natural and human-made background ambient noise can disturb the conveyance of information because of high noise levels. Noise cancellation, which is used frequently in audio technology, has limits in noise reduction and does not guarantee clear vocal pickup in these severe situations. A contact microphone that is attached directly to the medium of interest has the potential to pick up vocal signals with reduced noise. In this study, an electrostatic transducer with an elastomer layer that is impedance-matched to the human body is used to pick up speech sounds through constant contact on the chin and cheek. By attaching the wearable device directly to the skin, the medium of air is bypassed, and airborne noise is passively canceled. Because of the acoustic impedance-matched layer, the sensor is more sensitive to low frequencies under 500 Hz, so frequency equalization was implemented to flatten the frequency response throughout the vocal range. The perceptual evaluation of speech quality (PESQ) scores of the wearable device with equalization averaged around 2.6 on a scale from –0.5 to 4.5. Speech recordings were also collected in a noise field of 85 dB, and the performance was compared to a cardioid lapel mic, a cardioid dynamic mic, and an omnidirectional condenser mic. The recordings revealed a significantly reduced presence of white noise in the contact sensor. This study provides preliminary results that show potential vocal applications for a wearable impedance-matched sensor. Full article