How mesenchymal stem cells transform into adipocytes: Overview of the current understanding of adipogenic differentiation.

Mesenchymal stem cells (MSCs) are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts, chondrocytes and adipocytes. The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes, in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes. Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis. However, the mechanism underlying the adipogenic differentiation of MSCs is not fully understood. Here, the current knowledge of adipogenic differentiation in MSCs is reviewed, focusing on signaling pathways, noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation. Finally, the relationship between maladipogenic differentiation and diseases is briefly discussed. We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.

Evaluation of the Optimal Duration of Thumb Cupping Therapy for Frozen Shoulder by Thermal Metabolic Imaging.

Objective: To evaluate the optimal duration of thumb cupping therapy for frozen shoulder (FS) by thermal metabolic imaging (TMI) and to provide clinical evidence. Methods: From April 2022 to August 2023, 120 patients with FS who received thumb cupping therapy at our hospital were randomized into groups A, B, and C for 5, 10, and 15 minutes of cupping, respectively. The clinical efficacy, Visual Analogue Scale (VAS) score, and shoulder range of motion (ROM) of the three groups were compared, and the skin blood flow and the incidence of adverse reactions during treatment were analyzed. Finally, the temperature difference improvement efficiency (i.e., higher TMI after treatment than before treatment) was compared among the three groups. Results: Groups B and C showed higher overall clinical efficacy than group A (P < .05). After treatment, lower VAS scores were determined in groups B and C compared with group A, whereas the ROM values of groups A and C were smaller than those of group B Group C had the greatest skin blood flow and the highest incidence of adverse reactions (P < .05), while group B had the highest temperature difference improvement efficiency (P < .05). Conclusions: Through TMI, it is confirmed that thumb cupping therapy with a duration of 10 min contributes to the highest efficacy and safety for patients with FS.

Enhancing the Cooling Efficiency of Aluminum-Filled Epoxy Resin Rapid Tool by Changing Inner Surface Roughness of Cooling Channels.

In low-pressure wax injection molding, cooling time refers to the period during which the molten plastic inside the mold solidifies and cools down to a temperature where it can be safely ejected without deformation. However, cooling efficiency for the mass production of injection-molded wax patterns is crucial. This work aims to investigate the impact of varying surface roughness on the inner walls of the cooling channel on the cooling efficiency of an aluminum-filled epoxy resin rapid tool. It was found that the cooling time for the injection-molded products can be determined by the surface roughness according to the proposed prediction equation. Employing fiber laser processing on high-speed steel rods allows for the creation of microstructures with different surface roughness levels. Results demonstrate a clear link between the surface roughness of cooling channel walls and cooling time for molded wax patterns. Employing an aluminum-filled epoxy resin rapid tool with a surface roughness of 4.9 µm for low-pressure wax injection molding can save time, with a cooling efficiency improvement of approximately 34%. Utilizing an aluminum-filled epoxy resin rapid tool with a surface roughness of 4.9 µm on the inner walls of the cooling channel can save the cooling time by up to approximately 60%. These findings underscore the significant role of cooling channel surface roughness in optimizing injection molding processes for enhanced efficiency.

Isobaric Tags for Relative and Absolute Quantitation-Based Proteomics Analysis Revealed Proteins Involved in Drought Response during the Germination Stage in Faba Bean.

The faba bean, a significant cool-season edible legume crop, is susceptible to drought during the germination stage. Research regarding the genetic regulation of drought tolerance throughout this stage in the faba bean is limited. The differentially expressed proteins (DEPs) in faba beans between the drought-tolerant variety C105 and the drought-sensitive variant E1 during seed germination were identified in this work, accomplished through isobaric tags for relative and absolute quantitation (iTRAQ) analysis. A total of 3827 proteins were identified in the two varieties of germinating seeds. Compared to those of variety E1, an increase in 108 DEPs and a decrease in 61 DEPs were observed in variety C105 under drought. Conversely, in the control group, variety C105 showed 108 significantly upregulated DEPs and 55 significantly downregulated DEPs. GO and KEGG analyses showed that the DEPs associated with glutathione metabolism and protein processing demonstrated significant increases in response to drought stress. Protein-protein interaction (PPI) analysis unveiled three closely connected functional modules of protein translation, DNA replication, and post-translational modification, originating from 22 DEPs derived from the germination period of two varieties under drought stress. To verify the proteomic function, we selected three differentially expressed protein coding genes, which were overexpressed or silenced in tobacco, thereby enhancing the drought resistance of tobacco. This was accompanied via altered levels of superoxide dismutase or peroxidase in transgenic plants under drought stress. The possible mechanism for drought tolerance in germinating seeds of faba bean involves increasing protein translation, decreasing DNA replication, and modifying chromatin. These findings offer invaluable insights into the reaction mechanism in response to drought stress in faba beans. The identified DEPs could be utilized in faba bean breeding initiatives to manage drought.

A Review on Material Selection Benchmarking in GeTe-Based RF Phase-Change Switches for Each Layer.

The global demand for radio frequency (RF) modules and components has grown exponentially in recent decades. RF switches are the essential unit in RF front-end and reconfigurable systems leading to the rapid development of novel and advanced switch technology. Germanium telluride (GeTe), as one of the Chalcogenide phase-change materials, has been applied as an RF switch due to its low insertion loss, high isolation, fast switching speed, and low power consumption in recent years. In this review, an in-depth exploration of GeTe film characterization is presented, followed by a comparison of the device structure of directly heated and indirectly heated RF phase-change switches (RFPCSs). Focusing on the prototypical structure of indirectly heated RFPCSs as the reference, the intrinsic properties of each material layer and the rationale behind the material selection is analyzed. Furthermore, the design size of each material layer of the device and its subsequent RF performance are summarized. Finally, we cast our gaze toward the promising future prospects of RFPCS technology.

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk in vitro and in vivo. ACNVax, combined with anti-PD-1, achieved long-term tumor remission (>200 days) with 80% complete response in mice with HER2+ breast cancer. ACNVax not only remodeled the tumor immune microenvironment but also induced a long-term immune memory, as evidenced by complete rejection of tumor rechallenge and a high level of antigen-specific memory B, CD4, and CD8 cells in mice (>200 days). This study provides a cancer vaccine design strategy, using B/CD4 T cell epitopes in an antigen clustered topography, to achieve long-term durable anticancer efficacy through promoting B/CD4 T cell crosstalk.

Dynamic coordinated control strategy of a dual-motor hybrid electric vehicle based on clutch friction torque observer.

The hybrid power system with dual motors and multiple clutches experiences significant torque fluctuation during mode switching process due to the different torque response characteristics of the motor and engine. To address this issue, this paper focuses on the estimation of clutch friction torque and the development of dynamic coordinated control strategies for the components. Firstly, based on the dynamic model of the novel dual-motor hybrid electric vehicle, a torque observer based on the Kalman filter algorithm is developed to predict the friction torque generated in the clutch sliding friction stage. Secondly, the control strategies are developed for the mode switching process from single-motor to dual-motor and from dual-motor to parallel drive on a co-simulation platform. Thirdly, a power level Hardware-In-the-Loop test platform is built, and the performance of the designed control strategies is verified by the HIL platform. The results show that for the mode switching process from dual-motor to parallel drive, compared with the control strategy using the engine target speed, the control strategy based on engine idle speed proposed in this paper reduces the clutch sliding friction work and the maximum longitudinal jerk of the vehicle by 42.5% and 25.4%, respectively.

Molecular and metabolic responses to immune stress in the jejunum of broiler chickens: transcriptomic and metabolomic analysis.

In the large poultry industry, where farmed chickens are fed at high density, the prevalence of pathogens and repeated vaccinations induce immune stress, which can significantly decrease the production performance and increase the mortality. This study was designed to shed light on the molecular mechanisms and metabolic pathways involved in immune stress through an in-depth analysis of transcriptomic and metabolomic changes in jejunum samples from the broilers. Two groups were established for the experiment: a control group and an LPS group. LPS group received an intraperitoneal injection of LPS solution at a dose of 250 µg per kg at 12, 14, 33, and 35 d of age, whereas the control group received a sterile saline injection. The severity of immune stress was assessed using the Disease Activity Index. A jejunal section was collected to measure the intestinal villus structure (villus length and crypt depth). RNA sequencing and metabolomics data analysis were conducted to reveal differentially expressed genes and metabolites. The results showed that the DAI index was increased and jejunal villus height/crypt depth was decreased in the LPS group. A total of 96 differentially expressed genes and 672 differentially accumulating metabolites were detected in the jejunum by LPS group compared to the control group. The comprehensive analysis of metabolomic and transcriptomic data showed that 23 pathways were enriched in the jejunum and that appetite, nutrient absorption, energy and substance metabolism disorders and ferroptosis play an important role in immune stress in broilers. Our findings provide a deeper understanding of the molecular and metabolic responses in broilers to LPS-induced immune stress, suggesting potential targets for therapeutic strategies to improve the production performance of broiler chickens.

YAP1/TAZ Mediates Rumen Epithelial Cell Proliferation but Not Short-Chain Fatty Acid Metabolism In Vitro.

Promoting rumen development is closely related to the health and efficient growth of ruminants. The transcriptional co-activators Yes1-associated protein (YAP1) and WW domain-containing transcription regulator protein 1 (TAZ) are key regulators of the mammalian epithelium. In the present study, we assessed the impact of YAP1/TAZ on rumen epithelial (RE) cell proliferation using their activator GA-017 (GA) and inhibitor verteporfin (VP). We also investigated whether YAP1/TAZ-dependent alteration was involved in the RE developmental process induced by sodium butyrate (SB). The results indicated that GA promoted RE cell proliferation, while VP disrupted RE cell proliferation. The Hippo, Wnt, and calcium signaling pathways were altered following the regulation of YAP1/TAZ. Upon YAP1/TAZ activation, the expression of CCN1/2 increased. However, when YAP1/TAZ was inhibited, the expression of BIRC3 decreased. In the SB-treated cells, YAP1/TAZ-induced changes were not observed. SB increased the expressions of differentiated cell marker genes and genes involved in short-chain fatty acid (SCFA) metabolism, while YAP1/TAZ did not. Thus, YAP1/TAZ could be potential targets for regulating RE cell proliferation but not for SCFA metabolism. SB could not affect YAP1/TAZ. These findings broaden our understanding of the role of YAP1/TAZ and their regulators in RE development.

Erratum: [Corrigendum] Pien Tze Huang inhibits hypoxia­induced epithelial­mesenchymal transition in human colon carcinoma cells through suppression of the HIF­1 pathway.

[This corrects the article DOI: 10.3892/etm.2014.1549.].

Recent Advances in Nanotechnology-Based Strategies for Bone Tuberculosis Management.

Bone tuberculosis, an extrapulmonary manifestation of tuberculosis, presents unique treatment challenges, including its insidious onset and complex pathology. While advancements in anti-tubercular therapy have been made, the efficacy is often limited by difficulties in achieving targeted drug concentrations and avoiding systemic toxicity. The intricate bone structure and presence of granulomas further impede effective drug delivery. Nano-drug delivery systems have emerged as a promising alternative, offering the enhanced targeting of anti-tubercular drugs. These systems, characterized by their minute size and adaptable surface properties, can be tailored to improve drug solubility, stability, and bioavailability, while also responding to specific stimuli within the bone TB microenvironment for controlled drug release. Nano-drug delivery systems can encapsulate drugs for precise delivery to the infection site. A significant innovation is their integration with prosthetics or biomaterials, which aids in both drug delivery and bone reconstruction, addressing the infection and its osteological consequences. This review provides a comprehensive overview of the pathophysiology of bone tuberculosis and its current treatments, emphasizing their limitations. It then delves into the advancements in nano-drug delivery systems, discussing their design, functionality, and role in bone TB therapy. The review assesses their potential in preclinical research, particularly in targeted drug delivery, treatment efficacy, and a reduction of side effects. Finally, it highlights the transformative promise of nanotechnology in bone TB treatments and suggests future research directions in this evolving field.

Ginsenoside Rk3 Ameliorates Obesity-Induced Colitis by Modulating Lipid Metabolism in C57BL/6 Mice.

Lipid metabolism is closely related to obesity and its complications. Our previous study found that ginsenoside Rk3 (Rk3), a natural bioactive substance derived from ginseng, can effectively alleviate obesity-induced colitis, while its impact on the improvement of the lipid metabolism disorder remains unclear. Here, we demonstrated that Rk3 significantly alleviated inflammation, oxidative stress, and lipid dysregulation in high-fat diet-induced colitis C57BL/6 mice. The potential mechanism by which Rk3 mitigated colon inflammation in the context of obesity may involve the modulation of polyunsaturated fatty acid metabolism with specific attention to n-6 fatty acids, linoleic acid, and arachidonic acid. Rk3 intervention markedly reduced the production of pro-inflammatory factors (PGE2, PGD2, TXB2, HETE, and HODE) by inhibiting cyclooxygenase and lipoxygenase pathways, while enhancing the production of anti-inflammatory factors (EET and diHOME) via cytochrome P450 pathways. Our findings suggest that Rk3 is a potential anti-inflammatory natural drug that can improve obesity-induced intestinal inflammation by regulating lipid metabolism.

The body mass index and the risk of ectopic pregnancy: a 5-year retrospective case-control study.

PURPOSE: Acknowledging the associated risk factors may have a positive impact on reducing the incidence of ectopic pregnancy (EP). In recent years, body mass index (BMI) has been mentioned in research. However, few studies are available and controversial on the relationship between EP and BMI. METHODS: We retrospectively studied the EP women as a case group and the deliveries as a control group in the central hospital of Wuhan during 2017 ~ 2021. χ2 test of variables associated with ectopic pregnancy was performed to find differences. Univariate and multivariate binary logistic regression analysis was conducted to analyze the association of the variables of age, parity, history of induced abortion, history of ectopic pregnancy, history of spontaneous abortion, history of appendectomy surgery and BMI (< 18.5 kg/m2, 18.5 ~ 24.9 kg/m2, 25 kg/m2 ~ 29.9 kg/m2, ≥ 30 kg /m2) with EP. RESULTS: They were 659 EP and 1460 deliveries. The variables of age, parity, history of induced abortion, history of ectopic pregnancy and BMI were different significantly(P < 0.05). Multivariate analysis showed that the variables of age > 35 years old [(OR (Odds Ratio), 5.415; 95%CI (Confidence Interval), 4.006 ~ 7.320, P < 0.001], history of ectopic pregnancy (OR, 3.944; 95%CI, 2.405 ~ 6.467; P < 0.001), history of induced abortion(OR, 3.365; 95%CI, 2.724 ~ 4.158, P < 0.001) and low BMI (< 18.5 kg/m2) (OR, 1.929; 95%CI, 1.416 ~ 2.628, P < 0.001])increased the risk of EP. CONCLUSION: The history of ectopic pregnancy, history of induced abortion and age > 35 years old were the risk factors with EP. In addition to these traditional factors, we found low BMI (< 18.5 kg/m2) with women may increase the risk to EP.

High expression of TBRG4 in relation to unfavorable outcome and cell ferroptosis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of malignant liver tumor with poor prognosis. In this study, we investigated the expression of transforming growth factor beta regulator 4 (TBRG4) in HCC and its effects on the proliferation, invasion, and metastasis of HCC cells, and analyzed the possible molecular mechanisms. METHOD: Downloading the expression and clinical information of HCC samples in the TCGA database, analyzing the expression differences of TBRG4 by bioinformatics methods, analyzing the clinical relevance and prognostic significance. Performing GO, KEGG and GSEA enrichment analysis on the TBRG4-related gene set in patient HCC tissues. Applying cell counting, scratch test and Transwell experiment to study the biological function of TBRG4 in HCC. Mitochondrial membrane potential, apoptosis and ROS levels were evaluated to assess cell iron death. Western blot, RT-PCR, laser confocal microscopy and co-immunoprecipitation were used to detect and analyze the downstream signaling pathways and interacting molecules of TBRG4. RESULTS: Bioinformatics analysis revealed that TBRG4 was abnormally highly expressed in HCC tumor tissues and was associated with poor prognosis and metastasis in HCC patients. GO and KEGG functional enrichment analysis showed that TBRG4 was related to oxidative stress and NADH dehydrogenase (ubiquinone) activity. GSEA enrichment analysis showed that TBRG4 was associated with Beta catenin independent wnt signaling and B cell receptor. Functional experiments confirmed that knocking down TBRG4 could inhibit the proliferation, migration, and invasion of HCC cells. Mechanistically, TBRG4 inhibited the function of HCC cells through the DDX56/p-AKT/GSK3ß signaling pathway. In addition, interference with TBRG4 expression could reduce the mitochondrial membrane potential and accumulate ROS in HCC cells, leading to increased ferroptosis. Co-IP analysis showed that TBRG4 specifically bound to Beclin1. CONCLUSION: TBRG4 is highly expressed in HCC tumor tissues and is associated with poor prognosis. It may regulate the proliferation, invasion, and metastasis of HCC cells through the DDX56/p-AKT/GSK3ß signaling pathway. TBRG4 may interact with Beclin1 to regulate the ferroptosis of HCC cells.

Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C.

Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV.

Hydrogen bond unlocking-driven pore structure control for shifting multi-component gas separation function.

Purification of ethylene (C2H4) as the most extensive and output chemical, from complex multi-components is of great significance but highly challenging. Herein we demonstrate that precise pore structure tuning by controlling the network hydrogen bonds in two highly-related porous coordination networks can shift the efficient C2H4 separation function from C2H2/C2H4/C2H6 ternary mixture to CO2/C2H2/C2H4/C2H6 quaternary mixture system. Single-crystal X-ray diffraction revealed that the different amino groups on the triazolate ligands resulted in the change of the hydrogen bonding in the host network, which led to changes in the pore shape and pore chemistry. Gas adsorption isotherms, adsorption kinetics and gas-loaded crystal structure analysis indicated that the coordination network Zn-fa-atz (2) weakened the affinity for three C2 hydrocarbons synchronously including C2H4 but enhanced the CO2 adsorption due to the optimized CO2-host interaction and the faster CO2 diffusion, leading to effective C2H4 production from the CO2/C2H2/C2H4/C2H6 mixture in one step based on the experimental and simulated breakthrough data. Moreover, it can be shaped into spherical pellets with maintained porosity and separation performance.

A light-driven enzymatic enantioselective radical acylation.

Enzymes are recognized as exceptional catalysts for achieving high stereoselectivities1-3, but their ability to control the reactivity and stereoinduction of free radicals lags behind that of chemical catalysts4. Thiamine diphosphate (ThDP)-dependent enzymes5 are well-characterized systems that inspired the development of N-heterocyclic carbenes (NHCs)6-8 but have not yet been proved viable in asymmetric radical transformations. There is a lack of a biocompatible and general radical-generation mechanism, as nature prefers to avoid radicals that may be harmful to biological systems9. Here we repurpose a ThDP-dependent lyase as a stereoselective radical acyl transferase (RAT) through protein engineering and combination with organophotoredox catalysis10. Enzyme-bound ThDP-derived ketyl radicals are selectively generated through single-electron oxidation by a photoexcited organic dye and then cross-coupled with prochiral alkyl radicals with high enantioselectivity. Diverse chiral ketones are prepared from aldehydes and redox-active esters (35 examples, up to 97% enantiomeric excess (e.e.)) by this method. Mechanistic studies reveal that this previously elusive dual-enzyme catalysis/photocatalysis directs radicals with the unique ThDP cofactor and evolvable active site. This work not only expands the repertoire of biocatalysis but also provides a unique strategy for controlling radicals with enzymes, complementing existing chemical tools.