Abnormal Behavior Research Articles

Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders

Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), and pica, are psychobehavioral conditions characterized by abnormal eating behaviors and an excessive preoccupation with weight and body shape. This review examines changes in brain regions and functional connectivity in ED patients over the past decade (2013–2023) using resting-state functional magnetic resonance imaging (rs-fMRI). Key findings highlight alterations in brain networks such as the default mode network (DMN), central executive network (CEN), and emotion regulation network (ERN). In individuals with AN, there is reduced functional connectivity in areas associated with facial information processing and social cognition, alongside increased connectivity in regions linked to sensory stimulation, aesthetic judgment, and social anxiety. Conversely, BED patients show diminished connectivity in the dorsal anterior cingulate cortex within the salience network and increased connectivity in the posterior cingulate cortex and medial prefrontal cortex within the DMN. These findings suggest that rs-fMRI could serve as a valuable biomarker for assessing brain function and predicting treatment outcomes in EDs, paving the way for personalized therapeutic strategies.

Machine learning-based real-time anomaly detection using data pre-processing in the telemetry of server farms

Fast and accurate anomaly detection is critical in telemetry systems because it helps operators take appropriate actions in response to abnormal behaviours. However, recent techniques are accurate but not fast enough to deal with real-time data. There is a need to reduce the anomaly detection time, which motivates us to propose two new algorithms called AnDePeD (Anomaly Detector on Periodic Data) and AnDePed Pro. The novelty of the proposed algorithms lies in exploiting the periodic nature of data in anomaly detection. Our proposed algorithms apply a variational mode decomposition technique to find and extract periodic components from the original data before using Long Short-Term Memory neural networks to detect anomalies in the remainder time series. Furthermore, our methods include advanced techniques to eliminate prediction errors and automatically tune operational parameters. Extensive numerical results show that the proposed algorithms achieve comparable performance in terms of Precision, Recall, F-score, and MCC metrics while outperforming most of the state-of-the-art anomaly detection approaches in terms of initialisation delay and detection delay, which is favourable for practical applications.

Effects of different husbandry systems and attitudes of cattle farmers on the behavior and welfare of cattle in Germany

ABSTRACT This study examines the relationship between the attitude of cattle farmers toward their animals and the occurrence of behavioral and health problems in cattle. Various factors, including animal behavior, husbandry conditions and the frequency of diseases, are taken into account. The results of an online survey of 1,242 German cattle farmers indicated that a range of factors, including the husbandry system, the number of cattle, grazing practices and the human-animal relationship, can influence the occurrence of abnormal behavior in cattle, such as tongue play, mutual sucking, horse-like sitting and standing up as well as diseases, especially musculoskeletal disorders. Additionally, the study identified two distinct types of basic attitudes among livestock farmers toward cattle: emotional and utilitarian attitudes. A robust foundation between the attitude of the livestock owner and the husbandry conditions can therefore facilitate the welfare of cattle in terms of freedom from pain, disease and psychological suffering, as well as the expression of normal behavior. This, in turn, can reduce the occurrence of abnormal behavior.

6610 Emphasizing the evaluation of autonomic dysfunctioncontributes to the diagnosis of ROHHAD Syndrome -- Based on a comparative analysis of two center ROHHAD Syndrome case reports and reported literature

Abstract Disclosure: Y. Wang: None. L. Chen: None. C. Gong: None. Background: ROHHAD is the acronym of rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysfunction, it is an extremely rare and potentially fatal disease.The purpose of this study is to describe the clinical symptoms and timelines of ROHHAD syndrome. Methods: All patients with ROHHAD syndrome were included. Patients from 2007 to2019 published previously was regarded as group 1. We searched for the keyword "ROHHAD" in the PUMBED database, and included all literature describing theclinical symptoms of ROHHAD patients (group 2, from October 2019 to August 2023).We compared and analyzed the above two sets of data with our data (group 3). Results: In the past 2 years, we diagnosed 16 cases of ROHHAD syndrome totally, with a male to female ratio of 8:8. Mean BMI z score was 4.23 ± 1.70, and the age of rapid obesity was 3.17 (1.67, 7.92) years old, ranging from 3 to 22.5 kg/year. The age at which hypoventilation, hypothalamic dysfunction, and autonomic dysfunction occurred was 5.55 (3.61, 8.25) years old, 4.46 (1.83, 9.25) years old, 3.42 (1.83, 8.00) years old, respectively. The most common autonomic dysfunction were cardiovascular manifestations (13 cases), thermal dysregulation and excessive sweating (each with 11 cases). Totally 13 cases had emotional, cognitive and behavioral abnormalities, 7 cases had neurogenic tumors. Case 2 had neurogenic tumors more than 5 years before rapid obesity, cognitive and behavioral abnormalities more than 2 years ago. Case 10 had abnormal pain sensation shortly after birth, and following polyuria in 2 years before rapid obesity. A total of 116 patients including 100 cases previously reported and 16 cases in this study were analyzed. Compared with the incidence rates of rapid obesity, central hypoventilation and hypothalamic dysfunction in patients in this study, there was no statistically significant difference between three groups. Among patients who had autonomic dysfunction (group 1 vs group 2 vs group 3), thermal dysregulation was 65.7% vs 17.0% vs 68.8%, cardiovascular manifestations was NA vs 12.8% vs 81.2%, excessive sweating was 28.6% vs 10.6% vs 68.8%, gastrointestinal disturbances was 11.4% vs 8.5% vs 62.5%, strabismus was 25.7% vs 12.8% vs 62.5%, and sleep disturbance was NA vs 6.4% vs 50.0%, all p< 0.05. The incidence of abnormal emotion, cognition and behavior was NA vs 29.8% vs 81.2% (p<0.05). Conclusion: The incidence of autonomic dysfunction in 16 patients of this study is100%, with multiple manifestations of autonomic dysfunction coexisting. The incidenceof autonomic dysfunction and abnormal emotion, cognition and behavior in reportedcases from different eras were significantly lower than those of our study, indicating theimportance of fully evaluating the autonomic dysfunction and limbic system. Fewpatients may occur tumors or autonomic dysfunction before rapid obesity. Presentation: 6/3/2024

7753 Anoctamin 4 in the Area Postrema Regulates Glucose and Energy Homeostasis

Abstract Disclosure: L. Tu: None. Y. Xu: None. Located on the floor of the 4th ventricle within the dorsal surface of the medulla oblongata, the area postrema (AP) is a circumventricular organ where a proper blood-brain barrier is missing. Numerous studies reveal that neurons in the AP are implicated into suppression of food intake (e.g., glucagon-like peptide 1 (GLP-1)-mediated anorexia), but the role of AP neurons in whole-body glucose homeostasis is less investigated. Here we identified and fully characterized the physiological functions of anoctamin-4 (Ano4, a calcium activated chloride channel)1 in the AP. CRISPR-mediated deletion of Ano4 in the AP caused a lower body weight and reduced blood glucose, concurrent with an improved glucose tolerance and increased insulin sensitivity. Chemogenetic activation of Ano4-expressing neurons in the AP (APAno4) increased food intake and blood glucose, and did not induce conditioned flavor avoidance. Both Ano4 neurons and non-Ano4 neurons (i.e., neurons do not express Ano4) sent projections to the lateral parabrachial nucleus (LPBN). Optogenetic stimulation of APAno4 ◊ LPBN circuit promoted feeding behavior and increased blood glucose, whereas stimulation of APnon-Ano4 ◊ LPBN circuit inhibited food intake and did not influence glucose homeostasis. Finally, RNAscope studies reveal that 45.7% of APAno4 neurons are glutamatergic neurons, and 41.8% of them are GABAergic neurons. Furthermore, APAno4 neurons showed only a 2.6% overlap with Glp-1r-expressing neurons in the AP, but had a 60.8% co-localization with protein tyrosine phosphatase receptor δ2, which serves as orexigenic asprosin receptor. Together, our results indicate that Ano4 neurons in the AP are the first reported orexigenic neurons, and represent potential therapeutic targets for human diseases with glucose imbalance and abnormal feeding behavior. Reference: (1) Tu, L. et al. Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia. J Clin Invest 133,14. (2023). (2) Mishra, I. et al. Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor. Cell Metab 34, 549-563. (2022). Presentation: 6/2/2024

9207 Anoctamin 4 in the Area Postrema Regulates Glucose and Energy Homeostasis

Abstract Disclosure: L. Tu: None. Y. Xu: None. Located on the floor of the 4th ventricle within the dorsal surface of the medulla oblongata, the area postrema (AP) is a circumventricular organ where a proper blood-brain barrier is missing. Numerous studies reveal that neurons in the AP are implicated into suppression of food intake (e.g., glucagon-like peptide 1 (GLP-1)-mediated anorexia), but the role of AP neurons in whole-body glucose homeostasis is less investigated. Here we identified and fully characterized the physiological functions of anoctamin-4 (Ano4, a calcium activated chloride channel)1 in the AP. CRISPR-mediated deletion of Ano4 in the AP caused a lower body weight and reduced blood glucose, concurrent with an improved glucose tolerance and increased insulin sensitivity. Chemogenetic activation of Ano4-expressing neurons in the AP (APAno4) increased food intake and blood glucose, and did not induce conditioned flavor avoidance. Both Ano4 neurons and non-Ano4 neurons (i.e., neurons do not express Ano4) sent projections to the lateral parabrachial nucleus (LPBN). Optogenetic stimulation of APAno4 ◊ LPBN circuit promoted feeding behavior and increased blood glucose, whereas stimulation of APnon-Ano4 ◊ LPBN circuit inhibited food intake and did not influence glucose homeostasis. Finally, RNAscope studies reveal that 45.7% of APAno4 neurons are glutamatergic neurons, and 41.8% of them are GABAergic neurons. Furthermore, APAno4 neurons showed only a 2.6% overlap with Glp-1r-expressing neurons in the AP, but had a 60.8% co-localization with protein tyrosine phosphatase receptor δ2, which serves as orexigenic asprosin receptor. Together, our results indicate that Ano4 neurons in the AP are the first reported orexigenic neurons, and represent potential therapeutic targets for human diseases with glucose imbalance and abnormal feeding behavior. Reference: (1) Tu, L. et al. Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia. J Clin Invest 133,14. (2023). (2) Mishra, I. et al. Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor. Cell Metab 34, 549-563. (2022). Presentation: 6/2/2024

8585 Using Stimulants to Treat Childhood Obesity

Abstract Disclosure: C. Elatrash: None. S.R. Sisley: None. Background: Hyperphagia, characterized by excessive hunger, can significantly contribute to weight gain in early-onset childhood obesity and lacks an FDA-approved therapy. Stimulants commonly used in the treatment of attention deficit and hyperactivity disorder (ADHD) have a significant side effect of suppressing appetite. However, there is no data on the effectiveness of stimulants to reduce measures of obesity in children with severe obesity and hyperphagia. Methods: We retrospectively analyzed electronic medical records of children < 17 years old with severe, early-onset obesity (defined as a Body Mass Index (BMI) ≥ 120% of the 95th percentile (BMI%95th) prior to age 5 years) who were seen in the Genetic Disorders of Obesity Program (GDOP) at Texas Children’s Hospital (TCH). We included children who had a history of abnormal food behavior consistent with a clinical diagnosis of hyperphagia by having 2 of 9 symptoms of hyperphagia (consuming large portions, consistently feeling hungry, not feeling full with one serving, temper tantrums over food, asking for food frequently, sneaking food, getting up at night to eat, hiding food, constant asking for snacks) and were prescribed lisdexamfetamine treatment for hyperphagia for 6 months. We extracted BMI %95th for up to 12 months prior to treatment and 6 months after treatment. Paired t-tests were utilized to compare data from pre- vs. post-treatment. Results: Our cohort included 22 patients and was 68.2% female, 50% non-Hispanic White, 36.4% Hispanic white, and 13.6% black, with a mean age of 7.73 years±3.82 (range 3-17 years). There was a significant decrease in BMI%95th after treatment with lisdexamfetamine (167.3±38.8 vs. 158.0±40.2; p<0.001). We also observed a significant change in the rate of weight gain after lisdexamfetamine treatment; prior to treatment, patients gained 0.6 BMI%95th points/month compared to a loss of 1.9 points/month after treatment (p=0.002). 16 (72.72%) patients reported tolerable side effects, the rate of side effects was (33)33.33%. 19(57.57%) lasted from 1 week to 1 month and 6(18.18%) lasted more than 1 month. Side effects included adverse behavioral (9)27.27%, sleep disturbance (5)15.15%, and headache (4)12.12%. Conclusion: Children with severe obesity and clinical hyperphagia showed reductions in BMI%95th after six months of lisdexamfetamine treatment. Future research is needed to confirm the clinical efficacy of lisdexamfetamine in this high-risk population. Keywords: Childhood obesity, Stimulants, Hyperphagia, Pharmacologic Treatment Presentation: 6/3/2024

Investigation of Precipitation Behavior of a Novel Ni-Fe-Based Superalloy during High-Temperature Aging Treatment.

The precipitation behavior of a novel Ni-Fe-based superalloy developed for advanced ultra-supercritical (A-USC) coal-fired power plant applications during high-temperature aging treatment was investigated. The results showed that the major precipitates in the novel alloy were randomly distributed MC carbides, M23C6 carbides at grain boundaries, and the γ'-Ni3 (Al, Ti) phase in grain interiors after aging. MC remained relatively stable during both short-term and long-term aging. M23C6 quickly precipitated and exhibited a discrete distribution at grain boundaries during short-term aging, and partly developed into continuous films during long-term aging. After uniform precipitation, the shape of γ' remained spherical, and the size kept increasing with aging time according to the Lifshitz-Slyozov-Wagner (LSW) model. The hardness of the novel alloy was mainly associated with the precipitation behavior of γ'; as γ' gradually precipitated, the hardness steadily increased; after complete precipitation, as the size of γ' increased, the hardness first increased and then decreased, reaching the peak hardness when the average radius of γ' achieved the critical size. In addition, the novel alloy exhibited abnormal coarsening behavior at grain boundaries during both short-term and long-term aging. The coarsened grain boundaries were actually precipitate-free zones (PFZs) and the coarsened and elongated rod-like particles inside were identified as γ' precipitates. The mechanism of strain-induced grain boundary migration and the discontinuous coarsening reaction is proposed for the formation of PFZs. Furthermore, PFZs were considered to be potential crack sources during the creep rupture test, leading to earlier failure of the material.

Subclinical attention-deficit hyperactivity disorder symptoms and unhealthy lifestyle behaviours.

Literature emphasises the importance of identifying and intervening in the adoption of unhealthy lifestyle behaviours (ULBs) during adolescence at an early stage, to mitigate their long-term detrimental effects. Among the possible associated factors contributing to ULBs, attention-deficit hyperactivity disorder (ADHD) has been shown to play an important role. However, little is known about ADHD subclinical manifestations. The present study aimed to bridge the gap in the literature and shed light on the relationship between subclinical ADHD and early adoption of ULBs during adolescence. Through a clinimetric approach, prevalence of ULBs, severity of ADHD symptoms and psychosocial factors (i.e. allostatic overload, abnormal illness behaviour, quality of life, psychological well-being) were investigated among adolescents. The associations between different degrees of ADHD, ULBs and psychosocial factors were also explored. This multicentre cross-sectional study involved 440 adolescents (54.5% females; mean age 14.21 years) from six upper secondary schools. Participants completed self-report questionnaires on sociodemographic characteristics, ULBs, ADHD symptoms and psychosocial factors. The most common ULBs were energy drinks/alcohol consumption and problematic smartphone use. Of the sample, 22% showed subclinical ADHD and 20.2% showed clinical ADHD. The subclinical ADHD group showed several ULBs (i.e. altered mindful eating, impaired quality of sleep, problematic technology use) and psychosocial factors, akin to those of ADHD group and different from peers without ADHD symptoms. Since subclinical ADHD manifestation is associated with ULBs, similarly to clinical ADHD, identifying subthreshold symptoms during adolescence is crucial, as it could improve health-related outcomes in adulthood across different domains.

Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome

BackgroundPhelan-McDermid syndrome (PMS) is caused by monoallelic loss or inactivation at the SHANK3 gene, located in human chr 22q13.33, and is often associated with Autism Spectrum Disorder (ASD).ObjectivesTo assess the clinical and developmental phenotype in a novel sample of PMS patients, including for the first time auxometric trajectories and serotonin blood levels.Methods70 Italian PMS patients were clinically characterized by parental report, direct medical observation, and a thorough medical and psychodiagnostic protocol. Serotonin levels were measured in platelet-rich plasma by HPLC.ResultsOur sample includes 59 (84.3%) cases with chr. 22q13 terminal deletion, 5 (7.1%) disruptive SHANK3 mutations, and 6 (8.6%) ring chromosome 22. Intellectual disability was present in 69 (98.6%) cases, motor coordination disorder in 65 (92.9%), ASD in 20 (28.6%), and lifetime bipolar disorder in 12 (17.1%). Prenatal and postnatal complications were frequent (22.9%-48.6%). Expressive and receptive language were absent in 49 (70.0%) and 19 (27.1%) cases, respectively. Decreased pain sensitivity was reported in 56 (80.0%), hyperactivity in 49 (80.3%), abnormal sleep in 45 (64.3%), congenital dysmorphisms in 35 (58.3%), chronic stool abnormalities and especially constipation in 29 (41.4%). Parents reported noticing behavioral abnormalities during early childhood immediately after an infective episode in 34 (48.6%) patients. Brain MRI anomalies were observed in 53 (79.1%), EEG abnormalities in 16 (23.5%), kidney and upper urinary tract malformations in 18 (28.1%). Two novel phenotypes emerged: (a) a subgroup of 12/44 (27.3%) PMS patients displays smaller head size at enrollment (mean age 11.8 yrs) compared to their first year of neonatal life, documenting a deceleration of head growth (p < 0.001); (b) serotonin blood levels are significantly lower in 21 PMS patients compared to their 21 unaffected siblings (P < 0.05), and to 432 idiopathic ASD cases (p < 0.001).ConclusionsWe replicate and extend the description of many phenotypic characteristics present in PMS, and report two novel features: (1) growth trajectories are variable and head growth appears to slow down during childhood in some PMS patients; (2) serotonin blood levels are decreased in PMS, and not increased as frequently occurs in ASD. Further investigations of these novel features are under way.

Scaling of N-Type Field-Effect Transistors Based on Aligned Carbon Nanotube Arrays.

Wafer-scale aligned carbon nanotubes (A-CNTs) are promising candidate semiconductors for building high-performance complementary metal-oxide-semiconductor (CMOS) transistors for future integrated circuits (ICs). A-CNT-based p-type field-effect transistors (P-FETs) have demonstrated excellent performance and scalability down to sub-10 nm nodes. However, the development of A-CNT n-type FETs (N-FETs) lags far behind, in regard to their electronic performance and device scaling. In this work, we fabricated top-gated N-FETs based on A-CNTs with a scandium (Sc)-contacted source and drain. High-performance A-CNT N-FETs were demonstrated with record on-state current (Ion) exceeding 1 mA/μm and peak transconductance (gm) of 0.4 mS/μm. Interestingly, the A-CNT N-FETs exhibited abnormal scaling behavior owing to the lateral oxidation of low-work function source/drain contacts, leading to formidable challenges to scale both the gate length (Lg) and the contact length (Lc) at the same time. Understanding of the abnormal scaling behavior contributes to seeking solutions for high-performance A-CNT N-FETs, and it paves the way for future CNT CMOS digital IC technology.

Molecular diagnosis of patients with syndromic short stature identified by trio whole-exome sequencing.

Short stature is a complex disorder with phenotypic and genetic heterogeneity. This study aimed to investigate clinical phenotypes and molecular basis of a cohort of patients with short stature. Trio whole-exome sequencing (Trio-WES) was performed to explore the genetic aetiology and obtain a molecular diagnosis in twenty Chinese probands with syndromic and isolated short stature. Of the twenty probands, six (6/20, 30%) patients with syndromic short stature obtained a molecular diagnosis. One novel COMP pathogenic variant c.1359delC, p.N453fs*62 and one LZTR1 likely pathogenic variant c.509G>A, p.R170Q were identified in a patient with short stature and skeletal dysplasia. One novel de novo NAA15 pathogenic variant c.63T>G, p.Y21X and one novel de novo KMT2A pathogenic variant c.3516T>A, p.N1172K was identified in two probands with short stature, intellectual disability and abnormal behaviours, respectively. One patient with short stature, cataract, and muscle weakness had a de novo POLG pathogenic variant c.2863T>C, p.Y955H. One PHEX pathogenic variant c.1104G>A, p.W368X was identified in a patient with short stature and rickets. Maternal uniparental disomy 7 (mUPD7) was pathogenic in a patient with pre and postnatal growth retardation, wide forehead, triangular face, micrognathia and clinodactyly. Thirteen patients with isolated short stature had negative results. Trio-WES is an important strategy for identifying genetic variants and UPD in patients with syndromic short stature, in which dual genetic variants are existent in some individuals. It is important to differentiate between syndromic and isolated short stature. Genetic testing has a high yield for syndromic patients but low for isolated patients.

New CRISPR/Cas9-based Fgfr2C361Y/+ mouse model of Crouzon syndrome exhibits skull and behavioral abnormalities.

Crouzon syndrome (CS), a syndromic craniosynostosis, is a craniofacial developmental deformity caused by mutations in fibroblast growth factor receptor 2 (FGFR2). Previous CS mouse models constructed using traditional gene editing techniques faced issues such as low targeting efficiency, extended lineage cycles, and inconsistent and unstable phenotypes. In this study, a CRISPR/Cas9-mediated strategy was employed to induce a functional augmentation of the Fgfr2 point mutation in mice. Various techniques, including bone staining, micro-CT, histological methods, and behavioral experiments, were employed to systematically examine and corroborate phenotypic disparities between mutant mice (Fgfr2C361Y/+) and their wild-type littermates. Confirmed via PCR-Sanger sequencing, we successfully induced the p.Cys361Tyr missense mutation in the Fgfr2 IIIc isoform of the extracellular domain (corresponding to the p.Cys342Tyr mutation in humans) based on Fgfr2-215 transcript (ENSMUST00000122054.8). Fgfr2C361Y/+ mice exhibited characteristics consistent with the phenotypic features associated with CS, including skull-vault craniosynostosis, skull deformity, shallow orbits accompanied by exophthalmos, midface hypoplasia with malocclusion, and shortened skull base, notably without any apparent limb defects. Furthermore, mutant mice displayed behavioral abnormalities encompassing deficits in learning and memory, social interaction, and motor dysfunction, without anxiety-related disorders. Histopathological examination of the hippocampal region revealed structural abnormalities, suggesting possible brain development impairment secondary to craniosynostosis. In conclusion, we constructed a novel gene-edited Fgfr2C361Y/+ mice strain based on CRISPR/Cas9, which displayed skull and behavioral abnormalities, serving as a new model for studying genetic molecular mechanisms and exploring treatments for CS. KEY MESSAGES: CRISPR/Cas9 crafted a Crouzon model by enhancing Fgfr2-C361Y in mice. Fgfr2C361Y/+ mice replicate CS phenotypes-craniosynostosis and midface anomalies. Mutant mice show diverse behavioral abnormalities, impacting learning and memory. Fgfr2C361Y/+ mice offer a novel model for cranial suture studies and therapeutic exploration.

Quantitative mechanism of abnormal hardening behavior of Ti6Al4V alloy strengthened by ultrasonic surface rolling

In general, the outermost region of a metallic material has the highest hardness after surface mechanical strengthening. However, an abnormal surface hardening behavior was observed in Ti6Al4V alloy after the ultrasonic surface rolling process (USRP) in this work. The region with the highest surface hardening was not at the top surface but at the subsurface. By analyzing the distribution of grain size, dislocation density, texture, and kernel average misorientation (KAM) at different depths from the surface, and combining these findings with finite element analysis (FEA), the microstructural evolution underlying this abnormal surface hardening was elucidated. The microstructural characterization and FEA results indicate that the subsurface region underwent the most significant deformation. Subsequently, through the application of theoretical analysis, the potential mechanism of abnormal hardening of USRP treatment is described quantitatively for the first time. The results demonstrated that the hardening effect resulting from grain refinement was less pronounced, whereas the hardening effect resulting from dislocation pile-up was more prevalent. At the subsurface region of the USRP sample, a large number of interfaces resulted in the highest accumulation of dislocations in this area. Consequently, the subsurface region exhibited the highest microhardness, leading to the abnormal surface hardening phenomenon.

Abnormal resistivity behavior of Co–Cu alloys and responsible metastable liquid phase separation

The electrical resistivity of Co-Cu alloys with Cu content of 10, 20, 30, 40, 50, 60, 70, 80, and 90 at.% was measured in the temperature range from 1400 to 2100K. The experiments were performed during of heating and subsequent cooling of the samples. For alloys with Cu content of 30, 40, 60, 70, 80, and 90 at.%, a bend in the cooling curve specific to the liquid-liquid phase separation (LLPS) process was observed. LLPS is shown when the melt is undercooled to the binodal temperature T∗. The phase transition model of LLPS was proposed for to theoretically determine the temperatures T∗. The LLPS model demonstrates the possibility of percolation phenomena occurring in Cu-Co heterogeneous melts rich in cobalt. The LLPS model shows good agreement with experimental data and the abnormal resistivity behavior of Co–Cu alloys.

Amentoflavone Induces Ferroptosis to Alleviate Proliferation, Migration, Invasion and Inflammation in Rheumatoid Arthritis Fibroblast-like Synoviocytes by Inhibiting PIN1.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is prevalent worldwide and seriously threatens human health. RA-fibroblast-like synoviocytes (FLS) play important roles in almost all aspects of RA progression. This study aimed to study the effect of Amentoflavone (AMF), a polyphenol compound derived from extracts of Selaginella tamariscina, on the abnormal biological behaviors of RA-FLS. The immortalized human RA-FLS cell line (MH7A) was treated with AMF or transfected with small interfering RNAs (siRNAs) targeting peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Then, cell viability was detected by CCK-8 assay. EDU staining, wound healing and transwell assays were employed to measure the capacities of MH7A cell proliferation, migration and invasion. The levels of inflammatory factors were assessed using ELISA kits. Additionally, ferroptosis was analyzed by detecting Fe2+ content, lipid reactive oxygen species (ROS) level and expression of ferroptosis-related proteins. Pull-down assay was employed to verify the targeted binding of AMF to PIN1. Further, PIN1 overexpression or ferroptosis inhibitor Ferrostatin-1 (Fer-1) addition was conducted to elucidate the regulatory mechanism of AMF on PIN1 and ferroptosis. Results revealed that AMF intervention or PIN1 knockdown inhibited the proliferation, migration, invasion and inflammation in MH7A cells. AMF facilitated lipid peroxidation and ferroptosis in MH7A cells. Moreover, AMF targeted inhibition of PIN1 expression, and PIN1 overexpression restored the promoting effect of AMF on lipid peroxidation and ferroptosis in MH7A cells. Besides, Fer-1 reversed the impacts of AMF on the abnormal biological behaviors of MH7A cells. In summary, AMF induced ferroptosis to inhibit the proliferation, migration, invasion and inflammation in RA-FLS by inhibiting PIN1, providing a promising candidate for RA treatment.

Novel insights into presenilin 1 mutation associated with a distinctive dementia phenotype and cotton wool plaques.

The mutations in the presenilin 1 gene (PSEN1) are the main cause of familial Alzheimer's disease. PSEN1 mutations affect amyloid-beta peptide production, which accumulates in the brain as senile plaque and cotton wool plaques (CWPs) and relates to other neurodegenerative disorders. Here we report the second case of the PSEN1 G266S mutation, which showed distinctive neuropathological features, including abundant CWPs. Lewy body pathology, and altered amyloid-beta production. Using the proband's samples, we performed genetic analysis of the PSEN1, APP, MAPT, and APOE genes, histopathological and immunohistochemical analysis of the brain tissue, and biochemical analysis of Aβ production in COS cells transfected with wild-type or mutant PSEN1. The patient presented with memory loss, abnormal behavior, and visual hallucinations. Brain scans showed reduced blood flow, mild atrophy, and white matter lesions. Genetic analysis revealed a heterozygous mutation at codon 266 (G266S) of PSEN1 and polymorphism of MAPT (Q230R). The brain had many CWPs, severe cerebral amyloid angiopathy (CAA), senile plaque, Lewy bodies, and neurites. Electron microscopy displayed myelinated fiber degeneration, mitochondrial damage, and amyloid fibrils in the white matter. The production level of Aβ42 in PSEN1 G266S-transfected cells significantly increased. Our findings suggest that the PSEN1 G266S mutation may cause a heterogeneous clinical and pathological phenotype, influenced by other genetic or environmental factors.

An intelligent recognition method of factory personnel behavior based on deep learning

The real-time and accurate recognition of abnormal behavior among factory personnel helps enhance their awareness of hazardous environments, thereby reducing the occurrence of accidents. This paper proposes a behavior recognition network based on an attention mechanism and a high-efficiency convolution module. The Bi-Level Routing Attention was introduced to the backbone network, thus enhancing the attention of the recognition network to the target region effectively. The recognition accuracy was further strengthened by improving the neck network based on the ConvNeXt Block module while reducing the model complexity. Thirteen additional recognition models were constructed to enhance the original network from various perspectives. Subsequently, the mean average precision and detection speed of each model were evaluated. Experimental results demonstrated that the detection accuracy of the target recognition network proposed in this paper has been significantly improved, the detection speed meets the real-time requirements, and the comprehensive performance is the most superior compared with other diverse and improved networks. The proposed recognition model can accurately identify a variety of factory personnel's abnormal behaviors in real-time, and it has practical application significance for the problem of personnel safety identification in the factory.

Unveil the toxicity induced on early life stages of zebrafish (Danio rerio) exposed to 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers

The increased detection of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) in aquatic ecosystems, has raised concern worldwide about its possible negative impacts on wildlife. MDMA is produced as racemate but its enantioselective effects on non-target organisms are poorly understood. Therefore, this study aimed to provide a comprehensive study of the toxicity of MDMA and its enantiomers in the early life stages of zebrafish (Danio rerio). Zebrafish embryos (≈3 h post fertilization) were exposed to different concentrations (0.02, 0.2, 2, 20, and 200 μg/L) of (R,S)-MDMA and both pure enantiomers.Both enantiomers induced effects on embryonic development, DNA integrity, and behaviour and enantioselective effects were noted. (S)-MDMA exhibits higher toxic effects on embryonic development level with increased mortality and severity of teratogenic effects, and behavioural abnormalities in acoustic startle-habituation response. (R)-MDMA affected general activity and avoidance behaviour, showing greater inhibitory effects on behavioural activity. Additionally, (R,S)-MDMA induced higher genotoxic effects than the two isolated enantiomers. These results are of concern at populational levels since effects on mortality, development, and behaviour were observed even at environmentally relevant concentrations, which can cause a reduction of larval viability and in the number of individuals in each generation, and an increase in the risk of predation of the organisms. Yet, the bioaccumulation studies showed that MDMA is not accumulated in zebrafish.Therefore, this work demonstrated for the first time the occurrence of MDMA enantiotoxicity in the early life stages of zebrafish, which should be considered in further environmental risk assessments involving fish species or other non-target aquatic organisms.

Rotenone exposure causes features of Parkinson`s disease pathology linked with muscle atrophy in developing zebrafish embryo

Parkinson's disease (PD) is associated with both genetic and environmental factors; however, sporadic forms of PD account for > 90 % of cases, and PD prevalence has doubled in the past 25 years. Depending on the importance of the environmental factors, various neurotoxins are used to induce PD both in vivo and in vitro. Unlike other neurodegenerative diseases, PD can be induced in vivo using specific neurotoxic chemicals. However, no chemically induced PD model is available because of the sporadic nature of PD. Rotenone is a pesticide that accelerates the induction of PD and exhibits the highest toxicity in fish, unlike other pesticides. Therefore, in this study, we aimed to establish a model exhibiting PD pathologies such as dysfunction of DArgic neuron, aggregation of ɑ-synuclein, and behavioral abnormalities, which are known features of PD pathology, by rotenone exposure at an environmentally relevant concentration (30 nM) in developing zebrafish embryos. Our results provide direct evidence for the association between PD and muscle degeneration by confirming rotenone-induced muscle atrophy. Therefore, we conclude that the rotenone-induced model presents non-motor and motor defects with extensive studies related to muscle atrophy.