Mechanisms Of Differentiation Research Articles

Understanding the multi-functionality and tissue-specificity of decellularized dental pulp matrix hydrogels for endodontic regeneration

Dental pulp is the only soft tissue in the tooth which plays a crucial role in maintaining intrinsic multi-functional behaviors of the dentin-pulp complex. Nevertheless, the restoration of fully functional pulps after pulpitis or pulp necrosis, termed endodontic regeneration, remained a major challenge for decades. Therefore, a bioactive and in-situ injectable biomaterial is highly desired for tissue-engineered pulp regeneration. Herein, a decellularized matrix hydrogel derived from porcine dental pulps (pDDPM-G) was prepared and characterized through systematic comparison against the porcine decellularized nerve matrix hydrogel (pDNM-G). The pDDPM-G not only exhibited superior capabilities in facilitating multi-directional differentiation of dental pulp stem cells (DPSCs) during 3D culture, but also promoted regeneration of pulp-like tissues after DPSCs encapsulation and transplantation. Further comparative proteomic and transcriptome analyses revealed the differential compositions and potential mechanisms that endow the pDDPM-G with highly tissue-specific properties. Finally, it was realized that the abundant tenascin C (TNC) in pDDPM served as key factor responsible for the activation of Notch signaling cascades and promoted DPSCs odontoblastic differentiation. Overall, it is believed that pDDPM-G is a sort of multi-functional and tissue-specific hydrogel-based material that holds great promise in endodontic regeneration and clinical translation. Statement of significanceFunctional hydrogel-based biomaterials are highly desirable for endodontic regeneration treatments. Decellularized extracellular matrix (dECM) preserves most extracellular matrix components of its native tissue, exhibiting unique advantages in promoting tissue regeneration and functional restoration. In this study, we prepared a porcine dental pulp-derived dECM hydrogel (pDDPM-G), which exhibited superior performance in promoting odontogenesis, angiogenesis, and neurogenesis of the regenerating pulp-like tissue, further showed its tissue-specificity compared to the peripheral nerve-derived dECM hydrogel. In-depth proteomic and transcriptomic analyses revealed that the activation of tenascin C-Notch axis played an important role in facilitating odontogenic regeneration. This biomaterial-based study validated the great potential of the dental pulp-specific pDDPM-G for clinical applications, and provides a springboard for research strategies in ECM-related regenerative medicine.

Spatial Identification and Distribution Pattern of the Complexity of Rural Poverty in China Using Multisource Spatial Data

Regional poverty is one of the most serious challenges facing the world today. Poverty, antipoverty, and poverty alleviation are the focus of the attention of scholars and the public. This paper takes China’s counties as the research unit, selects the influencing factors of poverty from natural and socio-economic factors, establishes an evaluation index system, simulates the natural poverty index and socio-economic poverty eradication index of each county, and clarifies the distribution characteristics of spatial poverty using GIS spatial analysis and BP artificial neural network. The results indicate that natural factors are the main cause of poverty in Chinese counties, with 710 counties having a high natural poverty index, accounting for nearly 30% of the total number of counties in the country. The national county-level natural poverty index shows a clear strip distribution pattern along latitude and longitude, with a strip distribution from north to south and from west to east; socio-economic factors have played a certain role in poverty alleviation, with as many as 1521 counties with low socio-economic poverty alleviation indices, accounting for approximately 64% of the total number of counties in the country. The spatial distribution of the county-level socio-economic poverty alleviation index is relatively fragmented. Through spatial scanning statistics, a total of 44 county poverty pressure index risk clusters reached a statistical significance level, involving 243 counties and districts. In poverty reduction practice, the internal counties and districts of contiguous poverty-stricken areas should strengthen cooperation and exchange. In the process of poverty alleviation and development, targeted poverty alleviation and economic development should be carried out based on the poverty-dominant type and self-development ability of the county, in order to improve efficiency. Regions that are relatively prosperous and have taken the lead in poverty reduction should play a leading and exemplary role in strengthening the radiation power of regional central cities. The prominent feature of this study is the comprehensive utilization of multisource data and the use of new spatial analysis methods (flexible spatial scanning method is widely used in the field of infectious disease prevention and control research). By constructing a multidimensional poverty measurement system that includes natural and social factors, it distinguishes the differences between the factors that cause poverty and the factors that eliminate poverty in regional poverty. At the same time, the flexible spatial scanning detection method was used to detect the differentiation mechanism of poverty spatial patterns.

Monocyte to macrophage differentiation and changes in cellular redox homeostasis promote cell type-specific HIV latency reactivation

HIV latency regulation in monocytes and macrophages can vary according to signals directing differentiation, polarization, and function. To investigate these processes, we generated an HIV latency model in THP-1 monocytes and showed differential levels of HIV reactivation among clonal populations. Monocyte-to-macrophage differentiation of HIV-infected primary human CD14+ and THP-1 cells induced HIV reactivation and showed that virus production increased concomitant with macrophage differentiation. We applied the HIV-infected THP-1 monocyte-to-macrophage (MLat) model to assess the biological mechanisms regulating HIV latency dynamics during monocyte-to-macrophage differentiation. We pinpointed protein kinase C signaling pathway activation and Cyclin T1 upregulation as inherent differentiation mechanisms that regulate HIV latency reactivation. Macrophage polarization regulated latency, revealing proinflammatory M1 macrophages suppressed HIV reactivation while anti-inflammatory M2 macrophages promoted HIV reactivation. Because macrophages rely on reactive-oxygen species (ROS) to exert numerous cellular functions, we disrupted redox pathways and found that inhibitors of the thioredoxin (Trx) system acted as latency-promoting agents in T-cells and monocytes, but opposingly acted as latency-reversing agents in macrophages. We explored this mechanism with Auranofin, a clinical candidate for reducing HIV reservoirs, and demonstrated Trx reductase inhibition led to ROS induced NF-κB activity, which promoted HIV reactivation in macrophages, but not in T-cells and monocytes. Collectively, cell type-specific differences in HIV latency regulation could pose a barrier to HIV eradication strategies.

Stratification and prognostic evaluation of breast cancer subtypes defined by obesity-associated genes

ObjectiveBreast cancer was the most common type of cancer among women worldwide, significantly impacting their quality of life and survival rates. And obesity has been widely accepted as an important risk factor for breast cancer. However, the specific mechanisms by which obesity affects breast cancer were still unclear. Therefore, studying the impact mechanisms of obesity as a risk factor for breast cancer was of utmost importance.MethodsThis study was based on TCGA breast cancer RNA transcriptomic data and the GeneCard obesity gene set. Through single and multiple factor Cox analysis and LASSO coefficient screening, seven hub genes were identified. The independent mechanisms of these seven hub genes were evaluated from various aspects, including survival data, genetic mutation data, single-cell sequencing data, and immune cell data. Additionally, the risk prognosis model and the neural network diagnostic model were established to further investigate these seven hub genes. In order to achieve precision treatment for breast cancer (BRCA), based on the RNA transcriptomic data of the seven genes, 1226 BRCA patients were divided into two subtypes: BRCA subtype 1 and BRCA subtype 2. By studying and comparing the immune microenvironment, investigating the mechanisms of differential gene expression, and exploring the mechanisms of subnetworks, we aim to explore the clinical differences in the presentation of BRCA subtypes and achieve precision treatment for BRCA. Finally, qRT-PCR experiments were conducted to validate the conclusions of the bioinformatics analysis.ResultsThe 7 hub genes showed good diagnostic independence and can serve as excellent biomarkers for molecular diagnosis. However, they do not perform well as independent prognostic molecular markers for BRCA patients. When predicting the survival of BRCA patients, their AUC values at 1 year, 3 years, and 5 years are mostly below 0.5. Nevertheless, through the establishment of the risk prognosis model considering the combined effect of the seven hub genes, it was found that the survival prediction of BRCA patients can be significantly improved. The risk prognosis model, compared to the independent use of the seven hub genes as prognostic markers, achieved higher timeROC AUC values at 1 year, 3 years, and 5 years, with values of 0.651, 0.669, and 0.641 respectively. Additionally, the neural network diagnostic model constructed from the 7 genes performs well in diagnosing BRCA, with an AUC value of 0.94, accurately identifying BRCA patients. The two subtypes identified by the seven hub genes exhibited significant differences in survival period, with subtype 1 having a poor prognosis. The differential mechanisms between the two subtypes mainly originate from regulatory differences in the immune microenvironment. Finally, the results of this study’s bioinformatics analysis were validated through qRT-PCR experiments.Conclusion7 hub genes serve as excellent independent biomarkers for molecular diagnosis, and the neural network diagnostic model can accurately distinguish BRCA patients. In addition, based on the expression levels of these seven genes in BRCA patients, two subtypes can be reliably identified: BRCA subtype 1 and BRCA subtype 2, and these two subtypes showed significant differences in BRCA patient survival prognosis, proportion of immune cells, and expression levels of immune cells. Among them, patients with subtype 1 of BRCA had a poor prognosis.

Direct load control-based optimal scheduling strategy for demand response of air-conditioning systems in rural building complex

The abrupt surge in electricity consumption for air-conditioning (AC) in rural areas has exacerbated the rural power supply and demand imbalance, presenting a significant challenge to the reliability and stability of power provision in rural low-voltage grids. Implementing power demand response (DR) in buildings is recognized as an effective solution to address the grid's power imbalance and reliability issues. Among various building DR strategies, direct load control (DLC) stands out as a proficient approach to rapidly curtail building AC loads. However, applying this method solely to individual rural buildings proves less effective in peak regulation (PR). To fully exploit the DR potential of AC systems in rural building complex, it is essential to scale up the application of DLC. Consequently, a DLC-based DR optimal scheduling strategy is proposed for rural building complex AC systems. This strategy aims to meet PR demand and maximize the benefits for load aggregator. It establishes four DLC methods and differential compensation mechanisms, taking into account the varying thermal comfort requirements of AC users. The DR optimization model is solved using a genetic algorithm (GA), with PR demand derived from long and short-term memory neural network predictions. To validate the proposed strategy, a simulation study is conducted on a 200-unit farmhouse AC system, utilizing a typical rural soil source heat pump system in Xi'an, Shaanxi Province. The results demonstrate that the strategy surpasses the PR target by approximately 6.65 % during the DR period, while ensuring a minimum level of thermal comfort for all user categories. Additionally, it yields a PR benefit of 88.73 yuan per day for all users, thereby promoting the adoption of clean energy in rural areas.

LncRNA in periodontal tissue-derived cells on osteogenic differentiation in the periodontitis field.

Periodontitis can lead to the destruction of periodontal tissues and potentially tooth loss. Numerous periodontal tissue-derived cells display osteogenic differentiation potential. The presence of differentially expressed long non-coding RNAs (lncRNAs) in these cells indicate their ability to regulate the process of osteogenic differentiation. We aim to elucidate the various lncRNA-mediated regulatory mechanisms in the osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis at epigenetic modification, transcriptional, and post-transcriptional levels. We systematically searched the PubMed, Web of Science, and ScienceDirect databases to identify relevant literature in the field of periodontitis discussing the role of lncRNAs in regulating osteogenic differentiation of periodontal tissue-derived cells. The identified literature was subsequently summarized for comprehensive review. In this review, we have comprehensively summarized the regulatory mechanisms of lncRNAs in the osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis and discussed how these lncRNAs provide novel perspectives for understanding the pathogenesis and progression of periodontitis. These results indicate the pivotal role of lncRNAs as regulators in the osteogenic differentiation of periodontal tissue-derived cells, providing a solid basis for future investigations on the role of lncRNAs in the periodontitis field.

Elucidating the Role of circTIAM1 in Guangling Large-Tailed Sheep Adipocyte Proliferation and Differentiation via the miR-485-3p/PLCB1 Pathway.

Fat tissue-a vital energy storage organ-is intricately regulated by various factors, including circular RNA, which plays a significant role in modulating fat development and lipid metabolism. Therefore, this study aims to clarify the regulatory mechanism of sheep adipocyte proliferation and differentiation by investigating the involvement of circTIAM1, miR-485-3p, and its target gene PLCB1. Through previous sequencing data, circTIAM1 was identified in sheep adipocytes, with its circularization mechanism elucidated, confirming its cytoplasmic localization. Experimental evidence from RNase R treatment and transcription inhibitors highlighted that circTIAM1 is more stable than linear RNA. Additionally, circTIAM1 promoted sheep adipocyte proliferation and differentiation. Furthermore, bioinformatic analysis demonstrated a robust interaction between miR-485-3p and circTIAM1. Further experiments revealed that miR-485-3p inhibits fat cell proliferation and differentiation by inhibiting PLCB1, with circTIAM1 alleviating the inhibitory effect via competitive binding. In summary, our findings elucidate the mechanism through which circTIAM1 regulates Guangling Large-Tailed sheep adipocyte proliferation and differentiation via the miR-485-3p-PLCB1 pathway, offering a novel perspective for further exploring fat metabolism regulation.

A Systematic Investigation into the Optimization of Reactive Power in Distribution Networks Using the Improved Sparrow Search Algorithm–Particle Swarm Optimization Algorithm

With the expansion of the scale of electric power, high-quality electrical energy remains a crucial aspect of power system management and operation. The generation of reactive power is the primary cause of the decline in electrical energy quality. Therefore, optimization of reactive power in the power system becomes particularly important. The primary objective of this article is to create a multi-objective reactive power optimization (MORPO) model for distribution networks. The model aims to minimize reactive power loss, reduce the overall compensation required for reactive power devices, and minimize the total sum of node voltage deviations. To tackle the MORPO problems for distribution networks, the improved sparrow search algorithm–particle swarm optimization (ISSA-PSO) algorithm is proposed. Specifically, two improvements are proposed in this paper. The first is to introduce a chaotic mapping mechanism to enhance the diversity of the population during initialization. The second is to introduce a three-stage differential evolution mechanism to improve the global exploration capability of the algorithm. The proposed algorithm is tested on the IEEE 33-node system and the practical 22-node system. The results indicate a reduction of 32.71% in network losses for the IEEE 33-node system after optimization, and the average voltage of the circuit increases from 0.9485 p.u. to 0.9748 p.u. At the same time, optimization results in a reduction of 44.07% in network losses for the practical 22-node system, and the average voltage of the circuit increases from 0.9838 p.u. to 0.9921 p.u. Therefore, the proposed method exhibits better performance for reducing network losses and enhancing voltage levels.

Differential deformation mechanism of E–W‐trending Weiningbeishan fold‐thrust belt from central Ningxia, NW China

The Weiningbeishan fold‐thrust belt (WFTB), located in the transitional zone of the Tibetan Plateau, Alxa Block and Ordos Basin, is an ancient intracontinental orogenic belt. In this article, structural analysis is conducted to more finely reveal differential deformation between the Devonian and Carboniferous strata in the WFTB. We found that the E–W‐trending open folds are mainly developed in the Upper Devonian Zhongning Formation (D3z), while the E–W‐trending close and tight folds are mainly developed in the Carboniferous strata. The N–S minimum shortening strain of the bottom boundary of Member 2 of the Upper Devonian Zhongning Formation (D3z2) is 21.1%, whereas the N–S minimum shortening strain of the bottom boundary of Member 2 of the Upper Carboniferous Danliangshan Formation (C2d2) is 64.1%. We propose that the E–W‐trending open folds in the Upper Devonian Zhongning Formation (D3z) and E–W‐trending close and tight folds in the Carboniferous strata were formed under the N–S compression during the Middle–Late Triassic. The Zhangyigou and Laoyagou faults are the main tear faults to accommodate differential displacement on the surface between the Upper Devonian Zhongning Formation (D3z) in the east and Carboniferous strata in the middle, which change into a décollement fault in the deep part of the Dafosigou fold area in the middle to accommodate differential deformation between the deep Upper Devonian Zhongning Formation (D3z) and Carboniferous strata. This study enables us to better understand the Mesozoic intracontinental deformation in response to far‐field plate‐boundary convergence in NW China.

Inhibition of UHRF1 Improves Motor Function in Mice with Spinal Cord Injury

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.Graphical Downregulation of UHRF1 promotes the recovery of motor function in mice with spinal cord injury. By analyzing the RNA sequencing results of mice with spinal cord injury for 3 days and selecting UHRF1 for experimental validation, the study found that inhibiting UHRF1 can promote motor function recovery.

Garnet geochronology, major and trace element geochemistry of the Huanggangliang Fe-Sn polymetallic deposit, NE China

Cu-Fe (Au), W-Sn (Mo), Pb-Zn (Ag) and other element assemblages are common in many skarn deposits, but examples of Fe and Sn coexistence in nature are relatively rare. The Huanggangliang deposit in the southern Great Xing'an Range is the largest Fe-Sn polymetallic deposit in northern China, and there are five main mining areas (SK Ⅰ–SK Ⅴ) distributed along a SW–NE trend. SK Ⅰ and SK Ⅲ are the two larger mining areas in the Huanggangliang deposit, and their mineral assemblages and wall-rocks are significantly different: cassiterite and metal sulfides are duncommon in SK Ⅰ (andesite), while they are widely distributed in SK Ⅲ (marble). Garnet is widely distributed in SK Ⅰ and SK Ⅲ mining areas, and provides a good opportunity to explore the mechanism of Fe-Sn assemblage differentiation. Three types of garnet are distinguishable (Grt 1, Grt 2 and Grt 3) based on their mineral associations, textures and locations, and they mainly belong to the andradite-grossular solid solution series. The LA–ICP–MS U-Pb ages of the garnets from SK Ⅰ and SK Ⅲ are 136.0 ± 1.2 Ma (n = 25, MSWD = 1.9) and 136.2 ± 2.6 Ma (n = 37, MSWD = 1.8), respectively, suggesting that magmatic-hydrothermal activity in these two mining areas began at the same time. Grt 1 (located deep in SK Ⅰ and SK Ⅲ) and Grt 2 (located shallowly in SK Ⅰ) are mainly andradite, while Grt 3 (located shallowly in SK Ⅲ) is mainly grossular. They are all enriched in high field strength elements (HFSEs) and depleted in large ion lithophile elements (LILEs), and their REE patterns are enriched in light rare earth elements (LREEs) and depleted in heavy rare earth elements (HREEs). However, Grt Ⅰ-1a and 1b (deep garnets in SK Ⅰ) exhibit obvious positive Eu anomalies, while the other garnet types exhibit negative or no obvious Eu anomalies. Additionally, Grt 3 has high contents of V, Sn, U, Th, Zn and Y, and low contents of W and Mo. This pattern implies that the garnets in deep SK Ⅰ may have formed under oxidizing conditions with high temperatures, high oxygen fugacity (fO2) and weak acidity, while the garnets in shallow SK Ⅲ formed under reducing conditions with moderate temperatures, moderate fO2 and near-neutral pH. The garnets in shallow SK Ⅰ and deep SK Ⅲ may have formed under weak oxidation–reduction conditions at moderate to high temperatures, moderate fO2 and weakly acidic to neutral pH conditions. Our newly reported field geological, mineralogical, and geochemical data from garnet suggest that the ore-forming fluids of the Huanggangliang were magmatic-hydrothermal fluids mixed with slightly acidic external fluids, chloride complexes may have been the main transport ligands of REEs. The metallogenic environment may be an important factor leading to the difference of mineral assemblages in the Huanggangliang deposit.

Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes

Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185–80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity.

Differential mechanism between Listeria monocytogenes strains with different virulence contaminating ready-to-eat sausages during the simulated gastrointestinal tract

Listeria monocytogenes exhibits varying levels of pathogenicity when entering the host through contaminated food. However, little is known regarding the stress response and environmental tolerance mechanism of different virulence strains to host gastrointestinal (GI) stimuli. This study analyzed the differences in the survival and genes of stress responses among two strains of L. monocytogenes 10403S (serotype 1/2a, highly virulent strain) and M7 (serotype 4a, low-virulence strain) during simulated gastrointestinal digestion. The results indicated that L. monocytogenes 10403S showed greater acid and bile salt tolerance than L. monocytogenes M7, with higher survival rates and less cell deformation and cell membrane permeability during the in vitro digestion. KEGG analysis of the transcriptomes indicated that L. monocytogenes 10403S displayed significant activity in amino acid metabolism, such as glutamate and arginine, associated with acid tolerance. Additionally, L. monocytogenes 10403S demonstrated a higher efficacy in promoting activities that preserve bacterial cell membrane integrity and facilitate flagellar protein synthesis. These findings will contribute valuable practical insights into the tolerance distinctions among different virulence strains of L. monocytogenes in the GI environment.

Diel and Vertical Niche Differentiation of Frugivore Communities Feeding on Ficus nota (Blanco) Merr.

Ficus species are keystone species in tropical ecosystems for frugivores. Nonetheless, ecological aspects of fig frugivory such as niche differentiation are understudied, leading to huge gaps in the knowledge of fig-frugivore interactions. We used camera traps to monitor the vertical and diel activity of frugivores feeding on a Ficus nota tree in Cavite, the Philippines for 70 d to determine vertebrate species feeding on Ficus nota and their niche differentiation mechanisms. We observed several mammalian taxa (pteropodid fruit bats, Rattus sp. and Paradoxurus philippinensis) and several avian taxa (Hypsipetes philippinus, Pycnonotus goiavier, Lanius cristatus, and Centropus viridis). All of the detected species were observed to be perching on, inspecting, or eating fruits. However, based on existing literature, two of the four bird species detected (L. cristatus and C. viridis) are known to be carnivorous. Diel niche differentiation was evident from the diurnal and nocturnal activity patterns of birds and mammals, respectively. We also detected temporal activity differences between pteropodids and P. philippinensis, hence suggesting temporal niche differentiation. Pteropodids were also more active in the terrestrial stratum, whereas non-pteropodids were more active in the arboreal stratum, hence suggesting vertical niche differentiation. Diel niche differentiation may be attributed to differences in food acquisition adaptations, whereas vertical niche differentiation may be attributed to differences in tree morphology between strata and in frugivore adaptations for mobility. These results show that Ficus nota acts as a food source and habitat for frugivores and non-frugivores and that interspecific interactions are mediated by niche differentiation. Our findings underscore the potential of Ficus nota as a species in restoration efforts to support seed-dispersing frugivores and other wildlife species, as well as the utility of camera trapping to survey frugivores in understudied habitats.

Exploring Kinematic Bifurcations and Hinge Compliance for In‐Hand Manipulation: How Could Thick‐Panel Origami Contribute?

Origami‐inspired mechanisms have found significant applications in end effector design. So far, the exploration of thick‐panel origami has been relatively limited, but it is worth noting that the incorporation of rigid thick panels can introduce unique mechanical properties, showcasing great potential in addressing manipulation challenges. Our previous work has developed a gripper from thick‐panel waterbomb origami, which can pick up a variety of daily objects. Based on the same prototype, this article extends the gripper's function from grasping to in‐hand manipulation, which is attributed to the kinematic bifurcations and compliance of thick‐panel origami. A kinematic study is carried out to investigate the gripper's bifurcated motion modes. The hinge compliance is also taken into account to enhance the gripper's motion dexterity. Theoretical analysis and experiments are conducted to demonstrate both features, thereby paving the foundation for achieving dexterous motions with a simplified control strategy. Aided by a differential mechanism, the gripper can effectively interact with objects with the actuation inputs from only two motors. Objects including balls, cuboids, and cones are explored for in‐hand manipulation under different motion modes, showing varied trajectories. With the integration of tactile sensors at the fingertips, we have also revealed the gripper's potential for classification tasks.

Concordant B and T Cell Heterogeneity Inferred from the Multiomic Landscape of Peripheral Blood Mononuclear Cells in a Crohn's Disease Cohort.

Crohn's disease is characterized by inflammation in the gastrointestinal tract due to a combination of genetic, immune, and environmental factors. Transcriptomic and epigenomic profiling of intestinal tissue of Crohn's disease patients have revealed valuable insights into pathology, however have not been conducted jointly on less invasive peripheral blood mononuclear cells (PBMCs). Furthermore, the heterogeneous responses to treatments among individuals with Crohn's disease imply hidden diversity of pathological mechanisms. We employed single nucleus multiomic analysis, integrating both snRNA-seq and snATAC-seq of PBMCs with a variety of open source bioinformatics applications. Our findings reveal a diverse range of transcriptional signatures among individuals, highlighting the heterogeneity in PBMC profiles. Nevertheless, striking concordance between three heterogeneous groups was observed across B cells and T cells. Differential gene regulatory mechanisms partially explain these profiles, notably including a signature involving TGFß signaling in two individuals with Crohn's disease. A mutation mapped to a transcription factor binding site within a differentially accessible peak associated with the expression of this pathway, with implications for a personalized approach to understanding disease pathology. This study highlights how multiomic analysis can reveal common regulatory mechanisms that underlie heterogeneity of PBMC profiles, one of which may be specific to inflammatory disease.

Development, modeling and analysis of a differential lever-bridge amplification mechanism

The displacement amplification mechanism is commonly utilized in micro/nano-manipulating systems to enhance the output stroke of piezoelectric actuators. Aiming at large amplification ratio, this paper proposes a symmetrical dual-stage amplification mechanism consisting of a differential lever mechanism and a half-bridge mechanism. With consideration of the coupling effect between the dual-stage amplification mechanism, a kinematic modeling method is developed for the symmetrical differential lever-bridge hybrid (SDLBH) mechanism on top of the static balance and constraint conditions of the branch chain. In particular, the force-deformation relationship of the flexible hinge is derived according to the flexibility matrix method. Based on the path constraint conditions of the branch chain, the static equilibrium equation as well as the displacement constraint conditions are obtained. Consequently, the input-output model of the SDLBH mechanism is established, which is capable of accurately predicting the amplification ratio and the mechanical stiffness. Finite element simulations and real time experiments on the SDLBH prototype effectively validate the mechanical performance as well as the accuracy of proposed modeling method. The performance sensitivity of the developed SDLBH mechanism is further analyzed by the Taguchi method, aiming to offer the optimization guideline for real applications.

Sustained adenosine release: Revealing its impact on osteogenic signalling pathways of human mesenchymal stromal cells

Non-healing fractures, a global health concern arising from trauma, osteoporosis, and tumours, can lead to severe disabilities. Adenosine, integral to cellular energy metabolism, gains prominence in bone regeneration via adenosine A2B receptor activation. This study introduces a controlled-release system for localized adenosine delivery, fostering human mesenchymal stromal cell (hMSC) differentiation into functional bone cells. The study investigates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive media. Insights into adenosine-modulated signalling pathways during MSC differentiation, with osteogenic factors, provide a comprehensive understanding of the pathways involved. Analysing gene expression and metabolic profiles unravels adenosine's regulatory mechanisms in MSC differentiation. Sustained adenosine release from microparticles induces mineralization, synergizing with osteogenic media supplements, showcasing the potential of adenosine for treating critical bone defects and metabolic disorders. This study highlights the efficacy of a polymeric microparticle-based delivery system, offering novel strategies for bone repair. Unveiling adenosine's roles and associated signalling pathways advances our comprehension of molecular mechanisms steering bone regeneration, propelling innovative biomaterial, combined with metabolites, approaches for clinical use.

Integrative Metabolomic and Transcriptomic Analysis Elucidates That the Mechanism of Phytohormones Regulates Floral Bud Development in Alfalfa.

Floral bud growth influences seed yield and quality; however, the molecular mechanism underlying the development of floral buds in alfalfa (Medicago sativa) is still unclear. Here, we comprehensively analyzed the transcriptome and targeted metabolome across the early, mid, and late bud developmental stages (D1, D2, and D3) in alfalfa. The metabolomic results revealed that gibberellin (GA), auxin (IAA), cytokinin (CK), and jasmonic acid (JA) might play an essential role in the developmental stages of floral bud in alfalfa. Moreover, we identified some key genes associated with GA, IAA, CK, and JA biosynthesis, including CPS, KS, GA20ox, GA3ox, GA2ox, YUCCA6, amid, ALDH, IPT, CYP735A, LOX, AOC, OPR, MFP2, and JMT. Additionally, many candidate genes were detected in the GA, IAA, CK, and JA signaling pathways, including GID1, DELLA, TF, AUX1, AUX/IAA, ARF, GH3, SAUR, AHP, B-ARR, A-ARR, JAR1, JAZ, and MYC2. Furthermore, some TFs related to flower growth were screened in three groups, such as AP2/ERF-ERF, MYB, MADS-M-type, bHLH, NAC, WRKY, HSF, and LFY. The findings of this study revealed the potential mechanism of floral bud differentiation and development in alfalfa and established a theoretical foundation for improving the seed yield of alfalfa.

Integrated transcriptomic and lipidomic analysis provides key insights into lipid content changes during pecan (Carya illinoensis) fruit development.

Pecans [Carya illinoinensis (Wangenh.) K. Koch] are highly valued for their abundance of quality healthy lipids, positively impacting human health and making themselves a preferred choice for nutritionally rich foods. However, a comprehensive understanding of the high-resolution characteristics of pecan fruit lipid composition and its dynamic changes, as well as the transfer between embryo and pericarp during development, remains incomplete. In this study, through integrated multi-omics analysis, we observed significant spatiotemporal heterogeneity in lipid changes between the pericarp and embryo. It showed smaller fluctuations and more stable lipid levels in the pericarp while exhibiting a dynamic pattern of initially increasing and then decreasing lipid content in the embryo. In this study, a total of 52 differentially expressed genes were identified, related to fatty acid synthesis and metabolism pathways in the two tissues, with changes in oleic acid and linoleic acid composition being the primary features of the embryo. This research lays the foundation for further understanding the differential regulation mechanisms of lipid metabolism between embryo and pericarp. Overall, this study filled the knowledge gap regarding dynamic changes in pericarp lipid metabolites, provided crucial insights into the lipid metabolism network during pecan fruit development, and established a scientific basis for the genetic improvement of pecan crops.