Long-read and short-read RNA-seq reveal the transcriptional regulation characteristics of PICK1 in Baoshan pig testis.

PICK1 plays a crucial role in mammalian spermatogenesis. Here, we integrated single-molecule long-read and short-read sequencing to comprehensively examine PICK1 expression patterns in adult Baoshan pig (BS) testes. We identified the most important transcript ENSSSCT00000000120 of PICK1, obtaining its full-length coding sequence (CDS) spanning 1254 bp. Gene structure analysis located PICK1 on pig chromosome 5 with 14 exons. Protein structure analysis reflected that PICK1 consisted of 417 amino acids containing two conserved domains, PDZ and BAR_PICK1. Phylogenetic analysis underscored the evolutionary conservation and homology of PICK1 across different mammalian species. Evaluation of protein interaction network, KEGG, and GO pathways implied that interacted with 50 proteins, predominantly involved in glutamatergic synapses, amphetamine addiction, neuroactive ligand-receptor interactions, dopaminergic synapses, and synaptic vesicle recycling, and PICK1 exhibited significant correlation with DLG4 and TBC1D20. Functional annotation identified that PICK1 was involved in 9 GOs, including seven cellular components and two molecular functions. ceRNA network analysis suggested BS PICK1 was regulated by seven miRNA targets. Moreover, qPCR expression analysis across 15 tissues highlighted that PICK1 was highly expressed in the bulbourethral gland and testis. Subcellular localization analysis in ST (Swine Tesits) cells demonstrated that PICK1 significantly localized within the cytoplasm. Overall, our findings shed new light on PICK1's role in BS reproduction, providing a foundation for further functional studies of PICK1.

Unexplained splenomegaly as a diagnostic marker for a rare but severe disease with an innovative and highly effective new treatment option: A case report.

Acid Sphingomyelinase Deficiency (ASMD) is a lysosomal storage disorder that can lead to severe complications if not promptly treated. This case aims to highlight the critical importance of early awareness of ASMD and to introduce, for the first time in the literature, a new and highly effective treatment option for children.

Molecular determinants of phospholipid treatment to reduce intracellular cholesterol accumulation in NPC1 deficiency.

Niemann-Pick type C (NPC) disease, caused by mutations in the NPC1 or NPC2 genes, leads to abnormal intracellular cholesterol accumulation in late endosomes/lysosomes (LE/LY). Exogenous enrichment with lysobisphosphatidic acid (LBPA), also known as bis-monoacylglycerol phosphate or BMP, either directly or via the LBPA precursor phosphatidylglycerol (PG), has been investigated as a therapeutic intervention to reduce cholesterol accumulation in NPC disease. Here we report the effects of stereoisomer configuration and acyl chain composition of LBPA on cholesterol clearance in NPC1-deficient cells. We find that S,R, S,S, and S,R LBPA stereoisomers behaved similarly, with all 3 compounds leading to comparable reductions in filipin staining in two NPC1-deficient human fibroblast cell lines. Examination of several LBPA molecular species containing one or two mono- or polyunsaturated acyl chains showed that all LBPA species containing one 18:1 chain significantly reduced cholesterol accumulation, whereas the shorter chain species di-14:0 LBPA had little effect on cholesterol clearance in NPC1 deficient cells. Since cholesterol accumulation in NPC1 deficient cells can also be cleared by PG incubation, we used non-hydrolyzable PG analogues to determine whether conversion to LBPA is required for sterol clearance, or whether PG itself is effective. The results showed that non-hydrolyzable PG species were not appreciably converted to LBPA and showed virtually no cholesterol clearance efficacy in NPC1 deficient cells, supporting the notion that LBPA is the active agent promoting LE/LY cholesterol clearance. Overall these studies are helping to define the molecular requirements for potential therapeutic use of LBPA as an option for addressing NPC disease.

Decoupled High-Mobility Graphene on Cu(111)/Sapphire via Chemical Vapor Deposition.

The growth of high-quality graphene on flat and rigid templates, such as metal thin films on insulating wafers, is regarded as a key enabler for technologies based on 2D materials. In this work, the growth of decoupled graphene is introduced via non-reducing low-pressure chemical vapor deposition (LPCVD) on crystalline Cu(111) films deposited on sapphire. The resulting film is atomically flat, with no detectable cracks or ripples, and lies atop of a thin Cu2O layer, as confirmed by microscopy, diffraction, and spectroscopy analyses. Post-growth treatment of the partially decoupled graphene enables full and uniform oxidation of the interface, greatly simplifying subsequent transfer processes, particularly dry-pick up - a task that proves challenging when dealing with graphene directly synthesized on metallic Cu(111). Electrical transport measurements reveal high carrier mobility at room temperature, exceeding 104 cm2 V-1 s-1 on SiO2/Si and 105 cm2 V-1 s-1 upon encapsulation in hexagonal boron nitride (hBN). The demonstrated growth approach yields exceptional material quality, in line with micro-mechanically exfoliated graphene flakes, and thus paves the way toward large-scale production of pristine graphene suitable for high-performance next-generation applications.

Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.

Niemann-Pick disease type C1 (NP-C1) is a rare and devastating recessive inherited lysosomal lipid and cholesterol storage disorder caused by mutations in the NPC1 or NPC2 gene. These two proteins bind to cholesterol and cooperate in endosomal cholesterol transport. Characteristic clinical manifestations of NP-C1 include hepatosplenomegaly, progressive neurodegeneration, and ataxia. While the rarity of NP-C1 presents a significant obstacle to progress, researchers have developed numerous potential therapeutic approaches over the past two decades to address this condition. Various methods have been proposed and continuously improved to slow the progression of NP-C1, although they are currently at an animal or clinical experimental stage. This overview of NP-C1 therapy will delve into different theoretical treatment strategies, such as small molecule therapies, cell-based approaches, and gene therapy, highlighting the complex therapeutic challenges associated with this disorder.

Direct Multi-Target Teaching Interface for Autonomous Handling of Multi-Stack Logistics in a Warehouse.

This study presents a framework for enabling autonomous pick-place operations, addressing the need for efficiency in complex logistics environments using a direct multi-target teaching interface. First, tag and segmentation information were combined to recognize products in a complex warehouse, and a camera was installed on the rack to allow workers to remotely see the work environment, allowing workers to view the work environment in real time through a tablet. Workers can access the camera view showing the rack containing the target product through a swiping action and select the target product through direct teaching action. When the target product is finally selected, an optimal path is created through task planning, and an autonomous pick-place operation is performed based on the generated path. As a result of conducting a usability evaluation using the SUS (System Usability Scale) with six users on the interface that enables these tasks, it was confirmed that high user satisfaction was achieved with an average of 77.5 points. In conclusion, the proposed interface enhances operational efficiency and provides a user-friendly solution for complex warehouse tasks.

Equine ART and antral follicle count: Can we deepen our understanding to improve outcomes?

Assisted reproductive technologies (ARTs) are performed worldwide in the equine industry to produce genetically valuable foals. Among them, ovum pick up (OPU) combined with intra-cytoplasmic sperm injection (ICSI) can now be more efficient than embryo transfer (ET) under optimal conditions. However, OPU is not a benign procedure for the mare and the process is costly. Improved efficiency is therefore in the interest of everyone, maximizing mare welfare and optimizing economics for the client. One of the key factors of success is the antral follicle count (AFC) at the time of OPU and subsequently the number of oocytes obtained. Variations in AFC are reported between individuals and between geographical areas. This leads to a significant increase in numbers of embryos produced per session in some countries compared to others, independent of the laboratory efficiency. This article revisits the basics of folliculogenesis involved in establishment of the antral follicle population and explores work in other species given the paucity of equine research in this area. The aim of the review is to elucidate interesting areas of further research that could generate essential information for clinicians and clients about the management and selection of the donor mare for OPU and potentially identify pharmacological targets for manipulation.

Swine in vitro embryo production: Potential, challenges, and advances.

Pig production, a vital sector of the meat industry, faces demands for improved quality, efficiency, and sustainability. Advancements in breeding, disease control, and artificial insemination have enhanced production, while biotechnologies such as in vitro embryo production (IVP) and genetic engineering offer further progress. In vitro embryo production could facilitate the global exchange of valuable genetic material, accelerate breeding programs, and improve productivity, and it is essential for generating genetically modified (GM) pigs. These GM pigs have two main applications: first, they allow for targeted modifications aimed at improving production traits relevant to pig production in agriculture, such as meat quality and disease resistance. Second, they serve as valuable biomedical models for human disease research, regenerative medicine, and organ transplantation. Yet, despite notable advancements in recent decades, the efficiency of the current IVP systems for porcine embryos remains a challenge. Compared to the in vivo environment, suboptimal culture conditions lead to issues such as elevated polyspermy, poor embryo development, and the production of low-quality blastocysts. This review provides an overview of the key steps and recent advancements in porcine IVP technology. We will emphasize the promising utilization of oocytes from live females of high genetic value through ovum pick-up and the incorporation of extracellular vesicles and cytokines into IVP media. These innovative strategies hold immense potential to significantly enhance embryo development and overall success rates in porcine IVP, and could open the door for significant progress in both agriculture and biomedicine applications.

Study on the Technology of Laparoscopic Ovum Pick-Up and In Vitro Embryo Production in Chongming Goats.

The application of laparoscopic ovum pick-up (LOPU) and in vitro production of embryos (IVEP) technologies has opened up a new path for purebred breeding and breed improvement in goats. However, due to the complexity of the procedures and multiple influencing factors, these technologies have not been widely adopted in goat production. This study explores factors affecting the efficiency of LOPU in goats by comparing the use of controlled internal drug release (CIDR) for estrus synchronization, conventional FSH versus long-acting recombinant ovine FSH (R-FSH) for superovulation, and the timing of LOPU at 48 h, 60 h, and 72 h of follicular development. The metrics evaluated included the recovery rate of cumulus-oocyte complexes (COCs), the average number of ovarian follicles, the average number of COCs, and the average number of available COCs. The results demonstrated that the efficiency of LOPU was significantly higher with two doses of R-FSH compared to the conventional FSH superovulation protocol and the control group (p < 0.05), with two doses of R-FSH providing a higher LOPU efficiency than one dose (p < 0.05). Using CIDR for estrus synchronization showed no significant difference in LOPU efficiency compared to the non-CIDR group. Similarly, the efficiency of LOPU showed no significant difference between the hormone treatments at 48 h, 60 h, and 72 h. By exploring and optimizing the factors influencing LOPU, we ultimately established a LOPU technology system for goats that meets the production needs of small ruminants.

Recipients' and Environmental Factors Affecting the Pregnancy Rates of a Large, Fresh In Vitro Fertilization-Embryo Transfer Program for Dairy Cows in a Commercial Herd in China.

The main objective of this study was to determine the influence of the recipient dairy cows' breed, lactation number, estrus condition, the type, location and volume of the corpus luteum (CL) and the time of year that the embryo transfer (ET) was performed on the pregnancy rates of a large, fresh in vitro fertilization-embryo transfer program for dairy cows in a commercial herd in China. The recipients were from a herd of dairy cows in Ningxia, a province in northwest China, and we statistically analyzed the data of 495 cows from 2021 to 2023. Cumulus oocyte complexes (COCS) were isolated from follicular fluid obtained through ovum pick-up (OPU) and oocytes were incubated 20-22 h for in vitro maturation (IVM). Embryos were obtained after 10-12 h of in vitro fertilization (IVF) and six days of in vitro culture (IVC). Embryos at the morula or blastocyst stage were transferred to randomly chosen recipients (n = 495). The influence of recipients' breed (Holstein or other), recipients' lactation number (heifers or cows), estrus type (natural or synchronized), CL type (homogeneous, CLhom or cavitary, CLcav), CL side (left or right), volume of the CL and season of transfer (spring, autumn or winter) on pregnancy rates were determined. The pregnancy rates were analyzed by binomial logistic regression with IBM SPSS statistics software, version 26. Pregnancy rates after ET to Holstein cows and other breeds were 43.49% and 42.68%, respectively (p > 0.05). Regarding age, pregnancy rates were 45.56% for heifers and 30.77% for cows (p < 0.05). Pregnancy rates following ET during natural and synchronized estrus were 44.41% and 41.5%, respectively (p > 0.05). Pregnancy rates with a left- or right-side CL were 40.18% and 45.65%, respectively (p > 0.05). The pregnancy rates achieved with a CLhom and CLcav were 44.44% and 39.68%, respectively (p < 0.05). The rates obtained in spring, autumn and winter were 49.26%, 46.02% and 34.64%, respectively (p < 0.05). Moreover, it was found that pregnancy rates were higher in recipients with a CL volume measuring greater than 10 cm3 compared with those with a CL volume measuring less than 10 cm3 (p < 0.05). The comparisons showed that recipients' breed, estrus type or side of the CL had no effect, but the recipients' lactation number, ET season and the type and volume of the CL have significant effects on pregnancy rates during ET.

Graphene Microelectrode Arrays, 4D Structured Illumination Microscopy, and a Machine Learning Spike Sorting Algorithm Permit the Analysis of Ultrastructural Neuronal Changes During Neuronal Signaling in a Model of Niemann-Pick Disease Type C.

Simultaneously recording network activity and ultrastructural changes of the synapse is essential for advancing understanding of the basis of neuronal functions. However, the rapid millisecond-scale fluctuations in neuronal activity and the subtle sub-diffraction resolution changes of synaptic morphology pose significant challenges to this endeavor. Here, specially designed graphene microelectrode arrays (G-MEAs) are used, which are compatible with high spatial resolution imaging across various scales as well as permit high temporal resolution electrophysiological recordings to address these challenges. Furthermore, alongside G-MEAs, an easy-to-implement machine learning algorithm is developed to efficiently process the large datasets collected from MEA recordings. It is demonstrated that the combined use of G-MEAs, machine learning (ML) spike analysis, and 4D structured illumination microscopy (SIM) enables monitoring the impact of disease progression on hippocampal neurons which are treated with an intracellular cholesterol transport inhibitor mimicking Niemann-Pick disease type C (NPC), and show that synaptic boutons, compared to untreated controls, significantly increase in size, leading to a loss in neuronal signaling capacity.

Sublethal Effects of Pyridaben on the Predatory Function of Neoseiulus womersleyi.

Pyridaben is a widely utilized, broad-spectrum contact acaricide, which has notable sublethal effects that impair the predatory capabilities of predatory mites, but the specific mechanisms that affect the predatory functions remain underexplored. When predatory mites hunt for prey, they may rely on Niemann-Pick-type C2 (NPC2) proteins to collect herbivore-induced plant volatiles (HIPVs) and other odor molecules to locate and pursue their prey. This study elucidated that pyridaben significantly diminished the predatory efficiency and searching behavior of the predatory mite Neoseiulus womersleyi. Key metrics, including predatory capacity (a/Th) and predation rate (a) on various developmental stages of Tetranychus urticae, were markedly reduced in treated mites compared to controls. The searching efficiency (S) also declined proportionally with the increased sublethal dose of pyridaben. A gene linked to olfactive functions, NwNPC2a, was cloned from N. womersleyi. Post-treatment with pyridaben at LC30 and LC50 concentrations resulted in a substantial downregulation of NwNPC2a expression by 60.15% and 58.63%, respectively. Silencing NwNPC2a in N. womersleyi females led to significant reductions in the attack rate (a), handling time (Th), predation efficiency (a/Th), and maximum predation rate (1/Th). The searching efficiency (S) was also lower than that of the control group, displaying a slight decline with the increasing prey density. The findings revealed that pyridaben exerted inhibitory effects on both the predatory function and searching efficiency of N. womersleyi populations. The decrease in predatory performance at LC30 and LC50 concentrations was attributable to the suppression of NwNPC2a gene expression. RNA interference (RNAi) studies corroborated that the NwNPC2a gene plays a critical role in the predation process of N. womersleyi. Thus, the underlying molecular mechanism through which pyridaben compromises the predatory function of N. womersleyi likely involves the downregulation of NwNPC2a expression.

Combined removal of ovarian teratoma and oocyte retrieval by laparoscopic surgery under regional anesthesia.

OBJECTIVE: To describe the simultaneous laparoscopic approach for teratoma removal and oocyte retrieval performed under regional anesthesia in a woman, desiring to preserve fertility. The patient included in this video gave consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites, and other applicable sites. DESIGN: Video case report demonstrating the clinical management and laparoscopic teratoma removal combined with oocyte retrieval accomplished under regional anesthesia. SETTING: University tertiary care hospital. PATIENT(S): We present a case of a 31-year-old woman who referred to our Fertility Center with a previous history of right salpingo-oophorectomy for mucinous ovarian cystadenoma and the presence of a large ovarian teratoma of ten centimeters of the contralateral ovary. INTERVENTION(S): The ovarian stimulation started in the early follicular phase. Not being able to visualize follicular growth during the ovarian stimulation, it was decided to adopt fixed protocol with antagonist on the 5th day and to proceed, on 15th day, with a laparoscopic pick-up and simultaneous removal of the cyst. MAIN OUTCOME MEASURE(S): Laparoscopic surgery was performed: the left ovary appeared larger in size for the presence of the suspicious mature dermoid cyst and multiple follicles, previously not identified at ultrasound imaging. The follicles contained oocytes that were aspirated with an aspiration needle of 17 G connected to a craft suction pump. Then, practicing the stripping technique, an enucleation of the ovarian cyst was performed. Surprisingly, the removal of the cyst revealed other follicles that were readily aspirated. RESULT(S): The patient remained awake during the entire procedure and a low pressure of 10 mmHg was maintained at 15° of Trendelenburg position. A total of seven follicles were aspirated, seven oocytes were retrieved, and six mature oocytes were cryopreserved. The cyst was totally removed and no intracavitary spillage was caused. CONCLUSION(S): Simultaneous laparoscopic approach for teratoma removal and oocyte cryopreservation should be considered an effective fertility preservation strategy in patients in whom the presence of an ovarian neoformation does not allow visualization of growing follicles by ultrasound. Laparoscopic oocyte retrieval under regional anesthesia is a safe and well-tolerated technique and should be considered for patients where the transvaginal approach could not be performed.

The Possible Associations between Tauopathies and Atherosclerosis, Diabetes Mellitus, Dyslipidemias, Metabolic Syndrome and Niemann-Pick Disease.

Clinical evaluation and treatment of tauopathic syndromes remain a challenge. There is a growing interest in theories concerning their possible associations with metabolic diseases. The possible connection between those diseases might be linked with cerebrovascular dysfunction. The endothelial cell damage and impairment of the blood-brain barrier observed in atherosclerosis or diabetes may play a role in contributing to tauopathic syndrome development. Additionally, the inflammation evoked by pathological metabolic changes may also be involved in this process. Multiple cases indicate the coexistence of metabolic disorders and tauopathic syndromes. These findings suggest that modifying the evolution of metabolic and cerebrovascular diseases may impact the course of neurodegenerative diseases. Obtained data could indicate the possible benefits of introducing routine carotid artery sonography, revascularization operation or antihypertensive medications among patients at high risk for tauopathies. This review has identified this understudied area, which is currently associated with several diseases for which there is no treatment. Due to the pathomechanisms linking metabolic diseases and tauopathies, further investigation of this area of research, including cohort studies, is recommended and may provide new pharmacological perspectives for treatment.

Successful ultrasound-guided ovum pick-up (OPU) and subsequent in vitro embryo production in a domestic cat.

Ovum Pick Up (OPU) is a minimally invasive technique widely used in cattle and mares for oocyte retrieval, involving ultrasound-guided puncture of ovarian follicles. It has been demonstrated that this technique is safe for its repeated use in the same female without affecting her reproductive health, allowing for the retrieval of oocytes in individuals regardless of their reproductive status. The oocytes obtained through OPU can subsequently be used for in vitro embryo production (IVP) using assisted reproductive techniques (ARTs) or be cryopreserved in biobanks for their future use. Traditionally, the minimally invasive technique of choice performed in vivo in domestic and wild felines was LOPU (laparoscopic-guided ovum pick up). The present study was designed to explore if ultrasound-guided OPU in the domestic cat is safe and effective. In an initial series of ex vivo experiments (n = 92 ovaries, n = 434 oocytes), the effect of different aspiration pressures for oocyte collection was explored. These experiments identified 43 mmHg as the optimal aspiration pressure, resulting in the highest recovery rate and a favorable maturation and blastocyst rate. Subsequently, 16 grade I and II oocytes were retrieved by OPU and 101 oocytes were retrieved following ovariectomy and slicing. Sixteen oocytes obtained with each technique were subjected to in vitro maturation (IVM) and in vitro fertilization (IVF). A total of 14 presumptive zygotes were selected for in vitro culture (IVC) from each group (OPU and slicing), obtaining a cleavage rate of 57.1 % and 64.2 %, a morula rate of 28.5 % in both groups, and a blastocyst rate of 7.14 % and 14.2 % respectively. The hormonal stimulation protocol was well-tolerated, with no adverse effects observed. Moreover, no complications arose during the ovariectomy performed post-OPU. The use of this technique in domestic cats represents a significant step forward in terms of safety, replicability, and invasiveness, serving as a valuable model for its application in wild felids species. Additional research involving a greater number of animals is required to validate these encouraging findings.

Molecular basis of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a heterogeneous hematological malignancy characterized by clonal expansion of malignant plasma cells in the bone marrow. The disease is accompanied by various clinical manifestations, such as bone lesions, anemia, hypercalcemia, and renal insufficiency. However, despite significant advances in treatment over the last two decades, the disease remains challenging to treat, and most patients relapse. Although its pathogenesis has not yet been elucidated, it is clear that genomic instability plays a key role in its develop-ment or resistance to treatment. In some instances, the cause of this instability is chromothripsis, a form of complex genomic rearrangement that involves shattering and subsequent haphazard reassembly of chromosomes within a single catastrophic event. The resulting rearrangements involve a variety of structural changes, including deletions, duplications, inversions, and translocations, that lead to genome disruption. Specifically, these changes may result in alteration or inactivation of tumor suppressor genes (TP53 and CDKN2C), activation of oncogenes (MAF, FGFR3, and CCND1) or genes involved in key cellular processes. Unraveling the mechanisms that result in chromothripsis provides opportunities to identify critical genes and pathways involved in MM pathogenesis. These findings may serve as a basis for improved dia-gnostic approaches. PURPOSE: The goal of this review is to summarize the common primary and secondary chromosomal aberrations in MM with a particular focus on introducing complex chromosomal aberrations, especially chromothripsis in MM.

Acid sphingomyelinase deficiency in France: a retrospective survival study.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) or Niemann-Pick disease types A, A/B, and B is a progressive, life-limiting, autosomal recessive disorder caused by sphingomyelin phosphodiesterase 1 (SMPD1) gene mutations. There is a need to increase the understanding of morbidity and mortality across children to adults diagnosed with ASMD. METHODS: This observational retrospective survey analysed medical records of patients with ASMD with retrievable data from 27 hospitals in France, diagnosed/followed up between 1st January 1990 and 31st December 2020. Eligible records were abstracted to collect demographic, medical/developmental history, and mortality data. Survival outcomes were estimated from birth until death using Kaplan-Meier survival analyses; standardised mortality ratio (SMR) was also explored. RESULTS: A total of 118 medical records of patients with ASMD (type B [n = 94], type A [n = 15], and type A/B [n = 9]) were assessed. The majority of patients were males (63.6%); the median [range] age at diagnosis was 8.0 [1.0-18.0] months (type A), 1.0 [0-3] year (type A/B), and 5.5 [0-73] years (type B). Overall, 30 patients were deceased at the study completion date; the median [range] age at death for patients with ASMD type A (n = 14) was 1 [0-3.6] year, type A/B (n = 6) was 8.5 [3.0-30.9] years, and type B (n = 10) was 57.6 [3.4-74.1] years. The median [95% confidence interval (CI)] survival age from birth in patients with ASMD type A and type A/B was 2.0 [1.8-2.7] years and 11.4 [5.5-18.5] years, respectively. Survival analysis in ASMD type B was explored using SMR [95% CI] analysis (3.5 [1.6-5.9]), which showed that age-specific deaths in the ASMD type B population were 3.5 times more frequent than those in the general French population. The causes of death were mostly severe progressive neurodegeneration (type A: 16.7%), cancer (type B: 16.7%), or unspecified (across groups: 33.3%). CONCLUSIONS: This study illustrated a substantial burden of illness with high mortality rates in patients with ASMD, including adults with ASMD type B, in France.

Optimal Path Planning Algorithm with Built-In Velocity Profiling for Collaborative Robot.

This paper proposes a method for solving the path planning problem for a collaborative robot. The time-optimal, smooth, collision-free B-spline path is obtained by the application of a nature-inspired optimization algorithm. The proposed approach can be especially useful when moving items that are delicate or contain a liquid in an open container using a robotic arm. The goal of the optimization is to obtain the shortest execution time of the production cycle, taking into account the velocity, velocity and jerk limits, and the derivative continuity of the final trajectory. For this purpose, the velocity profiling algorithm for B-spline paths is proposed. The methodology has been applied to the production cycle optimization of the pick-and-place process using a collaborative robot. In comparison with point-to-point movement and the solution provided by the RRT* algorithm with the same velocity profiling to ensure the same motion limitations, the proposed path planning algorithm decreased the entire production cycle time by 11.28% and 57.5%, respectively. The obtained results have been examined in a simulation with the entire production cycle visualization. Moreover, the smoothness of the movement of the robotic arm has been validated experimentally using a robotic arm.

A novel prediction method for peak cutting force of curved picks considering lithological tolerances.

This study presents a 3D pick-rock contact calculation method for conical picks, aiming to develop a predictive method with high accuracy and lithological tolerance for peak cutting force (PCF). The method is based on the projection profile method and D. L. Sikarskie stress distribution function. By integrating Griffith's theory with rock damage constitutive model, the energy relationship between the rock fracturing process and crack propagation process is analyzed. Furthermore, in order to accurately correct the PCF, the energy correction function (C-Kf) is proposed to calculate the damage intensity index (Ke), which accounts for the relationship between rock brittleness and rock damage elastic-plastic energy. To validate the method, it is compared with full-scale cutting tests and three existing models, and statistical analysis confirms its high lithological tolerance and accuracy, the present model has the highest R2 of 0.90404, which is at least 12.5% higher relative to the mainstream models. Moreover, incorporating Ke into the method further enhances its predictive capability.

Besnoitia besnoiti tachyzoite replication in bovine primary endothelial cells relies on host Niemann-Pick type C protein 1 for cholesterol acquisition.

Besnoitia besnoiti is a cyst-forming apicomplexan parasite and the causal agent of bovine besnoitiosis. During early phase of infection, tachyzoites replicate within host endothelial cells in a host cell cholesterol-dependent process. By applying U18666A treatments, we here evaluated the role of Niemann-Pick type C protein 1 (NPC1) in both, intracellular B. besnoiti replication and host cellular cholesterol distribution. Additionally, B. besnoiti-driven changes in NPC1 gene transcription were studied by qPCR. Overall, U18666A treatments significantly reduced B. besnoiti proliferation and induced cholesterol accumulation in host cytoplasmic dense vesicles. However, NPC1 gene transcription was not affected by B. besnoiti infection.