Mechanisms Of Differentiation Research Articles

The Relationship Between Experiencing Childhood Trauma and Psychopathic Personality Traits: The Mediating Role of Insecure Attachment

ABSTRACT While psychopathy has been a topic of interest in the psychological field for a long time, it is still unclear which developmental factors are related to its onset. Theories have suggested that experiencing trauma in childhood may contribute to the development of psychopathic traits. Experiencing trauma may also contribute to the development of an insecure attachment style, which in turn might cause the emergence of psychopathic traits. The current study investigated links between experiencing childhood trauma and the three psychopathy domains of the Extended Levenson Self-Report Psychopathy scale (E-LSRP; Egocentricity, Callousness, and Antisocial), and whether these links were mediated by the four insecure attachment dimensions of the Attachment Style Questionnaire (ASQ; Need for Approval, Preoccupation with Relationships, Relationships as Secondary, and Discomfort with Closeness), in a large sample of non-clinical participants (N = 2023, Mage = 32.7, 70.0% female). The results suggested that Relationships as Secondary, but not Discomfort with Closeness, positively mediated the relationship between childhood trauma and the three domains of psychopathy, while Need for Approval negatively mediated this relationship. Preoccupation with Relationships was a significant mediator in the links between childhood trauma and both the Egocentricity and Antisocial domains, but not the Callousness domain. The current findings suggested that there might be both shared and differential mechanisms linking childhood trauma and psychopathic traits through insecure attachment styles. These findings can guide further investigations in longitudinal research.

Novel Multi‐configuration Elastic Actuator with Controllable Energy Flow and Power Modulation for Dynamic Energy Robot Systems

Designing actuators that can modulate power, achieve high energy efficiency, and ensure safe collision remains a challenge, especially for dynamic energy robot systems (DERS) with high‐performance requirements. Herein, a novel multi‐configuration elastic actuator (MCEA) is proposed based on a controllable planetary differential mechanism (PDM) with one power port from three springs. These springs, positioned between the inner gear ring and the fixed housing shell, are regulated by a single servo motor through a ratchet–pawl mechanism. This setup enables the springs to absorb energy during collisions, reducing impact and subsequently releasing this energy to boost power output. The inner gear ring functions as a controllable one‐way rotating element, acting either as an input or output for power. The MCEA's ability to manage power modulation and energy flow is demonstrated through experiments that highlight its potential for safe collision management, energy recycling, and power modulation. Experiment results indicate that the maximum output power of the MCEA in the proposed hybrid elastic actuation (HEA) mode is 8.05 times higher than that in the traditional actuation (TA) mode. A single‐legged robot with a four‐link mechanism is also built to validate the considerable performance in the application of legged robots, showing considerable adaptability and prospects for DERS.

Comparative study on pore-connectivity and wettability characteristics of the fresh-water and saline lacustrine tuffaceous shales: triggering mechanisms and multi-scale models for differential reservoir-forming patterns

Although particular attention has been paid to responses of hydrocarbon storage and percolation capacity to the devitrification concerning lacustrine tuffaceous shale reservoirs in recent years, there is still a lack of systematical and comparative investigation on differential patterns and potential triggering mechanisms concerning development of the pore-microfracture systems and characteristics of surface wettability between the fresh-water and saline lacustrine settings, which is of considerable importance in fully understanding of genesis and spatial distribution of dessert reservoir intervals of tuffaceous shale reservoirs, and to provide further conceptual basis for deciphering shale-oil movability of saline lacustrine fine-grained mixed sedimentary sequences. In this study, tuffaceous shales from both the Upper Triassic Yanchang Formation in the Ordos Basin and Middle Permian Jingjingzigou Formation in the Junggar Basin are targeted to unravel the differential behavior of tuff devitrification and potential impacts on reservoir wettability and pore connectivity concerning fresh-water and saline lacustrine settings, and we present new results here from integrated analyses and combined interpretation of FE-SEM, Image Pro Plus (IPP) software image processing, contact angle and spontaneous imbibition experiments. In view of comparative analysis from representative samples, the tuffaceous shales from saline lacustrine environments are characterized by well-developed intergranular-intercrystalline and dissolution pores, and inorganic microfractures, generally yield a higher plane porosity of representative pore-fracture spaces and spontaneous imbibition slopes, a relatively lower average of n-decane contact angles and corresponding wettability parameters. The saline lacustrine tuffaceous shales are thus suspected to have undergone more intense devitrification resulting in a higher amount of devitrification and associated dissolution pores, and a relatively better connectivity between isolated micropore systems with adjacent microfractures. This would significantly facilitate the interface wettability reversal and occurrence of movable hydrocarbon fluid in microscopic reservoir spaces. Finally, a comprehensive and conceptual model is established illustrating the effects of differential devitrification on reservoir-forming patterns concerning tuffaceous shales developed in the fresh-water and saline lacustrine settings, respectively. These findings are of great theoretical and practical significance to enrich theory of high-quality reservoir formation and shale-oil accumulation in saline lacustrine tuffaceous shale reservoirs, and lay the foundation for guiding efficient exploration of continental fine-grained mixed sedimentary sequences.

Distinguishing pathophysiological features of heart failure with reduced and preserved ejection fraction: A comparative analysis of two mouse models.

Heart failure (HF) is a heterogeneous condition that can be categorized according to the left ventricular ejection fraction (EF) into HF with reduced (HFrEF) or preserved (HFpEF) EF. Although HFrEF and HFpEF share some common clinical manifestations, the mechanisms underlying each phenotype are often found to be distinct. Identifying shared and divergent pathophysiological features might expand our insights on HF pathophysiology and assist the search for therapies for each HF subtype. In this study, we evaluated and contrasted two new murine models of non-ischaemic HFrEF and cardiometabolic HFpEF in terms of myocardial structure, left ventricular function, gene expression, cardiomyocyte calcium handling, mitochondrial polarization and protein acetylation in a head-to-head fashion. We found that in conditions of similar haemodynamic stress, the HFrEF myocardium underwent a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation was greater in the HFpEF myocardium. We observed opposing features on calcium release, which was diminished in the HFrEF cardiomyocyte but enhanced in the HFpEF cardiomyocyte. Mitochondria were less polarized in both HFrEF and HFpEF cardiomyocytes, reflecting similarly impaired metabolic capacity. Hyperacetylation of cardiac proteins was observed in both models, but it was more accentuated in the HFpEF heart. Despite shared features, unique triggering mechanisms (neurohormonal overactivation in HFrEF vs. inflammation in HFpEF) appear to determine the distinct phenotypes of HF. The findings of the present research stress the need for further exploration of the differential mechanisms underlying each HF subtype, because they might require specific therapeutic interventions. KEY POINTS: The mechanisms underlying heart failure with either reduced (HFrEF) or preserved (HFpEF) ejection fraction are often found to be different. Previous studies comparing pathophysiological traits between HFrEF and HFpEF have been conducted on animals of different ages and strains. The present research contrasted two age-matched mouse models of non-ischaemic HFrEF and cardiometabolic HFpEF to uncover divergent and shared features. We found that upon similar haemodynamic stress, the HFrEF heart experienced a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation appeared to be greater in the HFpEF myocardium. Calcium release was diminished in the HFrEF cardiomyocyte and enhanced in the HFpEF cardiomyocyte. Mitochondria were comparably less polarized in both HFrEF and HFpEF myocytes. Hyperacetylation of proteins was common to both models, but stronger in the HFpEF heart. Casting light on common and distinguishing features might ease the quest for phenotype-specific therapies for heart failure patients.

Design and evaluation of a four-DoF upper limb exoskeleton with gravity compensation

Gravity compensation (GC) mechanisms are commonly employed to either support limb gravity in passive exoskeletons or decrease motor power for safe human-robot interaction in active exoskeletons. This paper proposes a four-degree-of-freedom (DoF) upper limb exoskeleton with a theoretically perfect GC system, incorporating three DoFs in the shoulder and one DoF in the elbow. Paired with the anthropomorphic structure, the compact and adjustable GC system housed within the exoskeleton's linkages, reduces limitations on the limb's motion range and facilitates the integration of actuators for an active system. First, the GC system is designed through the analysis of potential energy equations, employing five cable-pulley-spring based units interconnected by parallel and differential mechanisms. Subsequently, the mechanical structure of the exoskeleton is developed, and the theoretically perfect GC in the quasi-static state is verified through numerical calculations. Then, the prototype is fabricated, and its actual performance is evaluated through experiments. The experimental results demonstrate the effectiveness of the exoskeleton with GC. Finally, a potential solution for the integration of actuators is demonstrated, and the limitation of the proposed system is also well discussed.

Sirtuin 3-activated superoxide dismutase 2 mediates fluoride-induced osteoblastic differentiation in vitro and in vivo by down-regulating reactive oxygen species.

Skeletal fluorosis is a chronic metabolic bone disease caused by long-term excessive fluoride intake. Abnormal differentiation of osteoblasts plays an important role in disease progression. Research on the mechanism of fluoride-mediated bone differentiation is necessary for the prevention and treatment of skeletal fluorosis. In the present study, a rat model of fluorosis was established by exposing it to drinking water containing 50mg/L F-. We found that fluoride promoted Runt-related transcription factor 2 (RUNX2) as well as superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) expression in osteoblasts of rat bone tissue. In vitro, we also found that 4mg/L sodium fluoride promoted osteogenesis-related indicators as well as SOD2 and SIRT3 expression in MG-63 and Saos-2 cells. In addition, we unexpectedly discovered that fluoride suppressed the levels of reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS) in osteoblasts. When SOD2 or SIRT3 was inhibited in MG-63 cells, fluoride-decreased ROS and mtROS were alleviated, which in turn inhibited fluoride-promoted osteogenic differentiation. In conclusion, our results suggest that SIRT3/SOD2 mediates fluoride-promoted osteoblastic differentiation by down-regulating reactive oxygen species.

Unraveling the differential mechanisms of revascularization promoted by MSCs & ECFCs from adipose tissue or umbilical cord in a murine model of critical limb-threatening ischemia

BackgroundCritical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral artery disease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities and elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities. Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization. However, the variability seen in several factors such as cell combinations or doses applied, have limited their success in clinical trials, being necessary to reach a consensus regarding the optimal “cellular-cocktail” prior further application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their regenerative properties.Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combination of endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) isolated from adipose-tissue (AT), compared with ECFCs from umbilical cord blood (CB-ECFCs) and AT-MSCs, in a murine model of CLTI.MethodsBalb-c nude mice (n:32) were distributed in four different groups (n:8/group): control shams, and ischemic mice (after femoral ligation) that received 50 µl of physiological serum alone or a cellular combination of AT-MSCs with either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carried out for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecular changes in response to CLTI and both cell combinations were analyzed in a proteomic quantitative approach.ResultsAT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 days post-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group presented the slowest ischemic progression along the assay. Moreover, many proteins involved in the repairing mechanisms promoted by cell treatments were identified.ConclusionsThe combination of AT-MSCs with AT-ECFCs or with CB-ECFCs promoted similar revascularization in CLTI mice, by restoring blood flow levels, together with the modulation of the inflammatory and necrotic processes, and reduction of muscle damage. The protein changes identified are representative of the molecular mechanisms involved in ECFCs and MSCs-induced revascularization (immune response, vascular repair, muscle regeneration, etc.).

Chromosome-level genome assembly of Hippophae rhamnoides variety

Fructus hippophae (Hippophae rhamnoides spp. mongolica×Hippophae rhamnoides sinensis), a hybrid variety of sea buckthorn that Hippophae rhamnoides spp. mongolica serves as the female parent and Hippophae rhamnoidessinensis serves as the male parent, is a traditional plant with great potentials of economic and medical values. Herein, we gained a chromosome-level genome of Fructus hippophae about 918.59 Mb, with the scaffolds N50 reaching 83.65 Mb. Then, we anchored 440 contigs with 97.17% of the total genome sequences onto 12 pseudochromosomes. Next, de-novo, homology and transcriptome assembly strategies were adopted for gene structure prediction. This predicted 36475 protein-coding genes, of which 36226 genes could be functionally annotated. Simultaneously, various strategies were used for quality assessment, both the complete BUSCO value (98.80%) and the mapping rate indicated the high assembly quality. Repetitive elements, which occupied 63.68% of the genome, and 1483600 bp of non-coding RNA were annotated. Here, we provide genomic information on female plants of a popular variety, which can provide data for pan-genomic construction of sea buckthorn and for the resolution of the mechanism of sex differentiation.

Biased gene introgression and adaptation in the face of chloroplast capture in Aquilegia amurensis.

Chloroplast capture, a phenomenon that can occur through interspecific hybridization and introgression, is frequently invoked to explain cytonuclear discordance in plants. However, relatively few studies have documented the mechanisms of cytonuclear coevolution and its potential for driving species differentiation and possible functional differences in the context of chloroplast capture. To address this crucial question, we chose the Aquilegia genus, which is known for having minimal sterility among species, and inferred that A. amurensis captured the plastome of A. parviflora based on cytonuclear discordance and gene flow between the two species. We focused on the introgression region and its differentiation from corresponding regions in closely related species, especially its composition in a chloroplast capture scenario. We found that nuclear genes encoding cytonuclear enzyme complexes (CECs; i.e., organelle-targeted genes) of chloroplast donor species were selectively retained and displaced the original CEC genes in chloroplast-receiving species due to cytonuclear interactions during introgression. Notably, the intrinsic correlation of CEC introgression was a greater degree of evolutionary distance for these CECs between A. amurensis and A. parviflora. Terpene synthase activity genes (GO: 0010333) were overrepresented among the introgressed genes, and more than 30% of these genes were CEC genes. These findings support our observations that floral terpene release pattern is similar between A. amurensis and A. parviflora compared with A. japonica. Our study clarifies the mechanisms of cytonuclear coevolution, species differentiation and functional differences in the context of chloroplast capture and highlights the potential role of chloroplast capture in adaptation.

Two C-terminal isoforms of Aplysia tachykinin-related peptide receptors exhibit phosphorylation-dependent and independent desensitization mechanisms

Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin (TK) signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their post-translational modifications were observed in extracts of CNS ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (TKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C-termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.

Comprehensive analysis of transcription factors involved in odontoblast differentiation mechanism.

Primary cultured odontoblasts rapidly lose their tissue-specific phenotype. To identify transcription factors (TF) that are important for the maintenance of the odontoblast phenotype, primary cultures of C57BL/6J mouse dental mesenchymal cells (DMC) were isolated, and expression of TF and odontoblast marker genes in cells immediately after isolation and 2days after culture were comprehensively evaluated and compared using RNA-sequencing (RNA-seq). The expression of odontoblast markers in mouse dental mesenchymal cells decreased rapidly after isolation. In addition, the expression of Hedgehog-related, Notch-related, and immediate- early gene (IEG)-related transcription factors significantly decreased. Forced expression of these genes in lentiviral vectors, together with fibroblast growth factor 4 (FGF4), fibroblast growth factor 9 (FGF9), and the Wnt pathway activator CHIR99021, significantly induced the expression of odontogenic marker genes. These results indicate, for the first time, that Notch signaling and early genes may be important for maintaining odontoblast cultures. Furthermore, simultaneous stimulation of FGF, Wnt, Hedgehog, Notch pathways, and IEG transcription factors cooperatively promoted the maintenance of the odontoblast phenotype. These results suggest that the Hedgehog and Notch signaling pathways may play an important role in maintaining odontoblast phenotypes, in addition to FGF and Wnt signaling.

An Effective Federated Object Detection Framework with Dynamic Differential Privacy

The proliferation of data across multiple domains necessitates the adoption of machine learning models that respect user privacy and data security, particularly in sensitive scenarios like surveillance and medical imaging. Federated learning (FL) offers a promising solution by decentralizing the learning process, allowing multiple participants to collaboratively train a model without sharing their data. However, when applied to complex tasks such as object detection, standard FL frameworks can fall short in balancing the dual demands of high accuracy and stringent privacy. This paper introduces a sophisticated federated object detection framework that incorporates advanced differential privacy mechanisms to enhance privacy protection. Our framework is designed to work effectively across heterogeneous and potentially large-scale datasets, characteristic of real-world environments. It integrates a novel adaptive differential privacy model that strategically adjusts the noise scale during the training process based on the sensitivity of the features being learned and the progression of the model’s accuracy. We present a detailed methodology that includes a privacy budget management system, which optimally allocates and tracks privacy expenditure throughout training cycles. Additionally, our approach employs a hybrid model aggregation technique that not only ensures robust privacy guarantees but also mitigates the degradation of object detection performance typically associated with DP. The effectiveness of our framework is demonstrated through extensive experiments on multiple benchmark datasets, including COCO and PASCAL VOC. Our results show that our framework not only adheres to strict DP standards but also achieves near-state-of-the-art object detection performance, underscoring its practical applicability. For example, in some settings, our method can lower the privacy success rate by 40% while maintaining high model accuracy. This study makes significant strides in advancing the field of privacy-preserving machine learning, especially in applications where user privacy cannot be compromised. The proposed framework sets a new benchmark for implementing federated learning in complex, privacy-sensitive tasks and opens avenues for future research in secure, decentralized machine learning technologies.

An Effective Federated Object Detection Framework with Dynamic Differential Privacy

The proliferation of data across multiple domains necessitates the adoption of machine learning models that respect user privacy and data security, particularly in sensitive scenarios like surveillance and medical imaging. Federated learning (FL) offers a promising solution by decentralizing the learning process, allowing multiple participants to collaboratively train a model without sharing their data. However, when applied to complex tasks such as object detection, standard FL frameworks can fall short in balancing the dual demands of high accuracy and stringent privacy. This paper introduces a sophisticated federated object detection framework that incorporates advanced differential privacy mechanisms to enhance privacy protection. Our framework is designed to work effectively across heterogeneous and potentially large-scale datasets, characteristic of real-world environments. It integrates a novel adaptive differential privacy model that strategically adjusts the noise scale during the training process based on the sensitivity of the features being learned and the progression of the model’s accuracy. We present a detailed methodology that includes a privacy budget management system, which optimally allocates and tracks privacy expenditure throughout training cycles. Additionally, our approach employs a hybrid model aggregation technique that not only ensures robust privacy guarantees but also mitigates the degradation of object detection performance typically associated with DP. The effectiveness of our framework is demonstrated through extensive experiments on multiple benchmark datasets, including COCO and PASCAL VOC. Our results show that our framework not only adheres to strict DP standards but also achieves near-state-of-the-art object detection performance, underscoring its practical applicability. For example, in some settings, our method can lower the privacy success rate by 40% while maintaining high model accuracy. This study makes significant strides in advancing the field of privacy-preserving machine learning, especially in applications where user privacy cannot be compromised. The proposed framework sets a new benchmark for implementing federated learning in complex, privacy-sensitive tasks and opens avenues for future research in secure, decentralized machine learning technologies.

Integrative analysis of transcriptome and metabolome reveal the differential tolerance mechanisms to low and high salinity in the roots of facultative halophyte Avicennia marina.

Mangroves perform a crucial ecological role along the tropical and subtropical coastal intertidal zone where salinity fluctuation is frequently happened. However, the differential responses of mangrove plant at transcriptome combined metabolome level to variable salinity are not well documented. In this study, we used Avicennia marina, a pioneer species of mangrove wetlands and one of the most salt-tolerant mangroves, to investigate the differential salt tolerance mechanisms under low and high salinity using ICP-MS, transcriptomic and metabolomic analysis. The results showed that HAK8 was up-regulated and transported K+ into the roots under low salinity. However, under high salinity, AKT1 and NHX2 were strongly induced, which indicated the transport of K+ and Na+ compartmentalization to maintain ion homeostasis. In addition, A. marina tolerates low salinity by up-regulating ABA signaling pathway and accumulating more mannitol, unsaturated fatty acids, amino acids, and L-ascorbic acid in the roots. Under high salinity, A. marina undergoes a more drastic metabolic network rearrangement in the roots, such as more L-ascorbic acid and oxiglutatione were up-regulated, while carbohydrates, lipids and amino acids were down-regulated in the roots, finally glycolysis and TCA cycle were promoted to provide more energy to improve salt tolerance. Our findings suggest that the major salt tolerance traits in A. marina can be attributed to complex regulatory and signaling mechanisms, and show significant differences between low and high salinity.

Differential Impairment Mechanism of Sperm Production via Induction of miR-34c-Activated Apoptosis and Spermatogenesis Pathway in Diet-Induced Obesity and Resistant Mice and GC-1 Spg Cells.

Male reproductive dysfunction is a clinical disease, with a large number of cases being idiopathic. Reproductive disorders have been found in obese (diet-induced obesity and diet-induced obesity-resistant) mice, but the mechanism behind the male reproductive dysfunction between them may be different. The purpose of this study was to explore the possible role and mechanism of miR-34c on sperm production in high-fat-diet-induced obesity-resistant (DIO-R) mice and GC-1 spg cells, which may differ from those in high-fat-diet-induced obesity (DIO) mice. In vivo and in vitro experiments were performed. C57BL/6J mice were fed a high-fat diet for 10 weeks to establish the DIO and DIO-R mouse model. GC-1 spg cells were used to verify the mechanism of miR-34c on sperm production. During in vivo experiments, sperm production damage was found in both DIO and DIO-R male mice. Compared to the control mice, significantly decreased levels of testosterone, LH, activities of acrosome enzyme (ACE), HAse, and activating transcription factor 1 (ATF1) were found in both DIO and DIO-R male mice (p < 0.05). Compared with the control group, the ratio of B-cell lymphoma-2 (Bcl-2)/bcl-2-associated X protein (Bax) in the DIO group was significantly decreased, and the expression level of cleaved caspase-3 was significantly increased (p < 0.05). Compared with the control group, the Bcl-2 protein expression level in the testes of the DIO-R group significantly decreased (p < 0.05). However, the Bax expression level increased. Thus, the Bcl-2/Bax ratio significantly decreased (p < 0.01); however, the factor-related apoptosis (Fas), Fas ligand (FasLG), cleaved caspase-8, caspase-8, cleaved caspase-3, and caspase-3 protein expression levels significantly increased (p < 0.05). Compared with the DIO group, in DIO-R mice, the activities of ACE, ATF1, Bcl-2, and Bcl-2/Bax's spermatogenesis protein expression decreased, while the apoptosis-promoting protein expression significantly increased (p < 0.05). During the in vitro experiment, the late and early apoptotic ratio in the miR-34c over-expression group increased. MiR-34c over-expression enhanced the expression of apoptosis-related proteins Fas/FasLG and Bax/Bcl-2 while inhibiting the expression of ATF1 and the sperm-associated protein in GC-1 spg cells. DIO and DIO-R could harm sperm production. DIO-R could impair sperm production by inducing the miR-34c-activated apoptosis and spermatogenesis pathway, which may be different from that of DIO.

Modulating efficient differentiation of neural stem cells into neurons by using plasmonic nanoparticles and the NIR II irradiation to boost therapy of Parkinson’s disease

Progressive loss of dopaminergic neurons is the primary pathological feature of Parkinson's disease (PD), which causes severe cognitive and motor dysfunction. In this context, transplantation of neural stem cells (NSCs) is the most promising approach to supply new dopaminergic neurons for the treatment of PD, which faces the challenge of precisely controlling the differentiation direction of NSCs. Herein, we report the efficient differentiation of NSCs into neurons boosted by the joint use of Cu2-xSe nanoparticles (CS NPs) with the second near-infrared (NIR-II) laser irradiation. We reveal the mechanism of neuronal differentiation of NSCs and find that the voltage-gated calcium channels (VGCC) of NSCs can be opened under the stimulation of CS NPs and NIR-II laser irradiation to trigger Ca2+/CaMK/CREB/c-Fos signaling pathway, which promotes the neural differentiation and survival. More importantly, when a mixture of CS NPs and NSCs was injected into the damaged striatum of 6-hydroxydopamine(6-OHDA)-induced PD mice and then irradiated with an external 1064 nm NIR-II laser, the NSCs were efficiently differentiated into dopaminergic neurons to effectively repair the damaged neural circuits in the nigra-striatum and ameliorate the motor disorders and anxiety of PD mice. These findings demonstrate the feasibility and importance of precise modulation of directional differentiation of NSCs into matured functional neurons in vivo and in vitro through advanced functional nanoparticles and nanotechnology, which offers a promising approach for the treatment of PD and other neurodegenerative diseases.

TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-β signaling plays a crucial role in various cellular processes, including growth, differentiation, apoptosis, epithelial-mesenchymal transition (EMT), regulation of the extracellular matrix, angiogenesis, and immune responses. TGF-β signals through SMAD proteins, which are intracellular molecules that transmit TGF-β signals from the cell membrane to the nucleus. Alterations in the TGF-β pathway and mutations in SMAD proteins are common in metastatic CRC (mCRC), making them critical factors in CRC tumorigenesis. This review first analyzes normal TGF-β signaling and then investigates its role in CRC pathogenesis, highlighting the mechanisms through which TGF-β influences metastasis development. TGF-β promotes neoangiogenesis via VEGF overexpression, pericyte differentiation, and other mechanisms. Additionally, TGF-β affects various elements of the tumor microenvironment, including T cells, fibroblasts, and macrophages, promoting immunosuppression and metastasis. Given its strategic role in multiple processes, we explored different strategies to target TGF-β in mCRC patients, aiming to identify new therapeutic options.

The Function and Mechanism of Long Noncoding RNAs in Adipogenic Differentiation

Adipocytes are crucial for maintaining energy balance. Adipocyte differentiation involves distinct stages, including the orientation stage, clone amplification stage, clone amplification termination stage, and terminal differentiation stage. Understanding the regulatory mechanisms governing adipogenic differentiation is essential for comprehending the physiological processes and identifying potential biomarkers and therapeutic targets for metabolic diseases, ultimately improving glucose and fat metabolism. Adipogenic differentiation is influenced not only by key factors such as hormones, the peroxisome proliferator-activated receptor (PPAR) family, and the CCATT enhancer-binding protein (C/EBP) family but also by noncoding RNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Among these, lncRNA has been identified as a significant regulator in adipogenic differentiation. Research has demonstrated various ways in which lncRNAs contribute to the molecular mechanisms of adipogenic differentiation. Throughout the adipogenesis process, lncRNAs modulate adipocyte differentiation and development by influencing relevant signaling pathways and transcription factors. This review provides a brief overview of the function and mechanism of lncRNAs in adipogenic differentiation.

Analysis and Experiment of Thermal Field Distribution and Thermal Deformation of Nut Rotary Ball Screw Transmission Mechanism

This study designs a differential dual-drive micro-feed mechanism, superposing the two “macro feed motions” (“motor drive screw” and “motor drive nut”) using the same transmission of “the nut rotary ball screw pair” structure. These two motions are almost equal in terms of speed and turning direction, thus the “micro feed” can be obtained. (1) Background: Thermal deformation is the primary factor that can restrict the high-precision micro-feed mechanism and the distribution of heat sources differs from that of the conventional screw single-drive system owing to the structure and motion features of the transmission components. (2) Discussion: This study explores the thermal field distribution and thermal deformation of the differentially driven micro-feed mechanism when two driving motors are combined at different speeds. (3) Methods: Based on the theory of heat transfer, the differential dual-drive system can be used as the research object. The thermal equilibrium equations of the micro-feed transmission system are established using the thermal resistance network method, and a thermal field distribution model is obtained. (4) Results: Combined with the mechanism of thermal deformation theory, the established thermal field model is used to predict the axial thermal deformation of the differential dual-drive ball screw. (5) Conclusions: Under the dual-drive condition, the steady-state thermal error of the nut-rotating ball screw transmission mechanism increases with the increase in nut speed and composite speed and is greater than the steady-state thermal error under the single screw drive condition. After reaching the thermal steady state, the measured thermal elongation at the end of the screw in the experiment is approximately 10.5 μm and the simulation result is 11.98 μm. The experimental measurement result demonstrates the accuracy of the theoretical analysis model for thermal error at the end of the screw.

Differential pattern of neurotoxicity induced by the gliadin peptides p31-43 and p57-68 in in vitro model of epilepsy

Epilepsy is a central nervous system (CNS) disorder causing repeated seizures due to a transient excessive or synchronous alteration in the electrical activity of the brain. Several neurological disorders have been associated to gluten-related diseases (GRD), including epilepsy. However, the molecular mechanisms that associate GRD and epileptogenesis are still unknown. Our previous data have shown that the gliadin peptide 31–43 (p31-43) enhanced number and duration of seizures induced by kainate in mice and exacerbated CA3-kainate-induced neurotoxicity in organotypic hippocampal slices. Here, we investigated whether another important gliadin peptide p57-68 may exerts effects similar to p31-43 on kainate-induced neurotoxicity. We find that both peptides exacerbate kainate-induced damage in the CA3 region once simultaneously challenged. However, after pre-incubation, p31-43 additionally exacerbates neurotoxicity in the CA1 region, while p57-68 does not. These data suggested differential intracellular mechanisms activated by the peptides. Indeed, analysing intracellular signalling pathways we discover that p31-43 induces significant intracellular changes, including increased phosphorylation of Akt, Erk1/2, and p65, decreased p38 phosphorylation, and deacetylation of nuclear histone-3. Based on these observations, we demonstrate that p31-43 likely activates specific intracellular signaling pathways involved in neuronal excitability, inflammation, and epigenetic regulation, which may contribute to its exacerbation of kainate-induced neurotoxicity. In contrast, p57-68 appears to exert its effects through different mechanisms. Further research is necessary to elucidate the precise mechanisms by which these peptides influence neurotoxicity and understand their implications for neurological disorders.