Cytosolic Cadherin 4 promotes angiogenesis and metastasis in papillary thyroid cancer by suppressing the ubiquitination/degradation of ß-catenin.

BACKGROUND: Although the long-term prognosis of papillary thyroid cancer (PTC) is favorable, distant metastasis significantly compromises the prognosis and quality of life for patients with PTC. The Cadherin family plays a pivotal role in tumor metastasis; however, the involvement of Cadherin 4 (CDH4) in the metastatic cascade remains elusive. METHODS: The expression and subcellular localization of CDH4 were determined through immunohistochemistry, immunofluorescence, and western blot analyses. The impact of CDH4 on cell migration, invasion, angiogenesis, and metastasis was assessed using transwell assays, tube formation assays, and animal experiments. Immunoprecipitation assay and mass spectrometry were employed to examine protein associations. The influence of CDH4 on the subcellular expression of ß-catenin and active ß-catenin was investigated via western blotting and immunofluorescence. Protein stability and ubiquitination assay were employed to verify the impact of CDH4 on ß-catenin degradation. Rescue experiments were performed to ensure the significance of CDH4 in regulating nuclear ß-catenin signaling. RESULTS: CDH4 was found to be significantly overexpressed in PTC tissues and predominantly localized in the cytoplasm. Furthermore, the overexpression of CDH4 in tumor tissues is associated with lymph node metastasis in PTC patients. Cytosolic CDH4 promoted the migration, invasion, and lung metastasis of PTC cells and stimulated the angiogenesis and tumorigenesis of PTC; however, this effect could be reversed by Tegavivint, an antagonist of ß-catenin. Mechanistically, cytosolic CDH4 disrupted the interaction between ß-catenin and ß-TrCP1, consequently impeding the ubiquitination process of ß-catenin and activating the nuclear ß-catenin signaling. CONCLUSIONS: CDH4 induces PTC angiogenesis and metastasis via the inhibition of ß-TrCP1-dependent ubiquitination of ß-Catenin.

Groundwater resistant gene accumulation in mining-agriculture complex zones: Insights from metagenomic analysis of subterranean mineral and terrestrial agricultural interactions.

During the Mining-Agriculture Complex Areas, the mining and agriculture activities could lead to an excessive presence of sulfate content in the regional groundwater. Sulfate exhibits the potential to influence the positive accumulation of RGs, although its mechanisms remain inadequately explored. To address this gap, this study analyzed the RGs buildup mechanisms in the groundwater of the mining-agriculture complex area. Results showed a widespread presence of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs), especially in coal-seams crevice groundwater. And iron and sulfur are primary environmental factors conducive to RGs accumulation through a synergistic interaction. Microbial annotation of gene sets sourced from coal-seams crevice groundwater samples unveiled part of sulfur-metabolizing microorganisms that were hosts of both ARGs and MRGs. Mechanistic insights revealed that iron may stimulates reactive oxygen species (ROS) generation, facilitating RGs accumulation, while adjusting sulfur metabolism and the synthesis of iron-sulfur clusters, thereby augmenting microbial growth which as predominant hosts of RGs, thereby intensifying the buildup of RGs.

The application of autofluorescence system contributes to the preservation of parathyroid function during thyroid surgery.

PURPOSE: The purpose of this study was to investigate the impact of autofluorescence technology on postoperative parathyroid function and short-term outcomes in patients undergoing thyroid surgery. METHODS: A total of 546 patients were included in the study, with 287 in the conventional treatment group and 259 in the autofluorescence group. Both groups underwent central lymph node dissection, which is known to affect parathyroid function. Short-term outcomes, including rates of postoperative hypocalcemia and parathyroid dysfunction, serum calcium and PTH levels on the first postoperative day, as well as the need for calcium supplementation, were analyzed. A multivariable analysis was also conducted to assess the impact of autofluorescence on postoperative parathyroid dysfunction, considering factors such as age, BMI, and preoperative calcium levels. RESULTS: The autofluorescence group demonstrated significantly lower rates of postoperative hypocalcemia and parathyroid dysfunction compared to the conventional treatment group. The autofluorescence group also had better serum calcium and PTH levels on the first postoperative day, and a reduced need for calcium supplementation. Surprisingly, the use of autofluorescence technology did not prolong surgical time; instead, it led to a shorter hospitalization duration. The multivariable analysis showed that autofluorescence significantly reduced the risk of postoperative parathyroid dysfunction, while factors such as age, BMI, and preoperative calcium levels did not show a significant correlation. CONCLUSION: This study provides evidence that autofluorescence technology can improve the preservation of parathyroid function during thyroid surgery, leading to better short-term outcomes and reduced postoperative complications. The findings highlight the potential of autofluorescence as a valuable tool in the management of parathyroid hypofunction. Further research and validation are needed to establish the routine use of autofluorescence technology in the thyroid.

Response of seed germination, seedling growth and physiological characteristics to alkali stress in halophyte Suaeda liaotungensis.

Soil salinization has been considered as a major environmental threat to plant growth. Different types of salt in saline soil have different effects on germination and seedling growth. Effect of NaCl on germination and seedling establishment in Suaeda liaotungensis have been reported, but its response to alkali stress remains unclear. Our results showed that brown seeds had higher germination rate, however, black seeds had higher germination recovery percentage under alkali stress. Na2CO3 had stronger inhibitory effect on germination and seedling growth than NaHCO3. As the concentration of alkali stress increased, the ROS level of brown seeds gradually ascended, while that of black seeds decreased first and then ascended. MDA content of dimorphic seeds significantly increased under alkali stress. The trend of SOD, POD and CAT activity between dimorphic seeds was similar under the same type of alkali stress. Alkali stress enhanced proline content of dimorphic seeds, and dimorphic seeds in NaHCO3 solution had higher proline content than Na2CO3 solution. Moreover, radicle and shoot tolerance indexes of seedlings in NaHCO3 solution were significantly higher than that of Na2CO3 solution. Under strong alkali stress, seedlings in NaHCO3 solution had significantly lower ROS level and MDA content as well as higher antioxidant enzyme activity than Na2CO3 solution. This study comprehensively compared the morphological and physiological characteristics in germination and seedlings to better reveal the saline-alkali tolerance mechanisms in S. liaotungensis.

Degradation of Nitrobenzene by Mackinawite through a Sequential Two-Step Reduction and Oxidation Process.

Mackinawite (FeS) has gained increasing interest due to its potential application in contaminant removal by either reduction or oxidation processes. This study further demonstrated the efficiency of FeS in degrading nitrobenzene (ArNO2) via a sequential two-step reduction and oxidation process under neutral conditions. In the reduction stage, FeS rapidly reduced ArNO2 to aniline (ArNH2), with nitrosobenzene (ArNO) and phenylhydroxylamine (ArNHOH) serving as the intermediates. X-ray photoelectron spectroscopy (XPS) analysis indicated that both Fe(II) and S(II) in FeS contributed electrons to the reduction of ArNO2. In the subsequent oxidation stage with oxygen, by addition of 0.5 mM tripolyphosphate (TPP), ArNH2 generated in the reduction process could be effectively oxidized to aminophenols by hydroxyl radicals (•OH), which would undergo eventual mineralization via ring-cleavage reactions. TPP exerted a favorable role in enhancing •OH production for ArNH2 degradation by promoting the formation of the dissolved Fe(II)-TPP complex, thus enhancing the homogeneous Fenton reaction. Additionally, TPP adsorption inhibited the surface oxidation reactivity of FeS due to the change of Fe(II) coordination. Finally, the effective degradation of ArNO2 by FeS in actual groundwater was demonstrated by using this sequential reduction and oxidation approach. These research findings provide a theoretical basis for a new FeS-based remediation approach, offering an alternative way for comprehensive removal of ArNO2.

The Evolution of Single-Cell RNA Sequencing Technology and Application: Progress and Perspectives.

As an emerging sequencing technology, single-cell RNA sequencing (scRNA-Seq) has become a powerful tool for describing cell subpopulation classification and cell heterogeneity by achieving high-throughput and multidimensional analysis of individual cells and circumventing the shortcomings of traditional sequencing for detecting the average transcript level of cell populations. It has been applied to life science and medicine research fields such as tracking dynamic cell differentiation, revealing sensitive effector cells, and key molecular events of diseases. This review focuses on the recent technological innovations in scRNA-Seq, highlighting the latest research results with scRNA-Seq as the core technology in frontier research areas such as embryology, histology, oncology, and immunology. In addition, this review outlines the prospects for its innovative application in traditional Chinese medicine (TCM) research and discusses the key issues currently being addressed by scRNA-Seq and its great potential for exploring disease diagnostic targets and uncovering drug therapeutic targets in combination with multiomics technologies.

Rapid classification and identification of chemical components of Astragali radix by UPLC-Q-TOF-MS.

INTRODUCTION: Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. OBJECTIVE: To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. METHODS: The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. Firstly, fragmentation information was obtained in the positive and negative ion modes. Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. RESULTS: A total of 45 chemical constituents were successfully screened out, including 22 flavonoids, 13 saponins, and 10 amino acids. CONCLUSION: The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR.

[Establishment and verification of quality evaluation method of Jizhi Syrup based on quantitative analysis of multi-components by single marker].

A quantitative analysis of multi-components by single marker(QAMS) method was established for the simultaneous determination of ephedrine hydrochloride, protocatechuic acid, 5-caffeoylquinic acid, 4-hydroxybenzoic acid, naringin, neohesperidin, glycyrrhizic acid, and praeruptorin A in Jizhi Syrup by high performance liquid chromatography(HPLC) with ultraviolet multi-wavelength detection system, and its feasibility in quality evaluation of Jizhi syrup was verified. With naringin as the internal reference substance, the relative correction factors and chromatographic peak localization methods of other seven components were respectively established at 210, 254, 280, and 320 nm. The method reproducibility was validated, and the result of QAMS were compared with those obtained by the external standard method(ESM) to verify the accuracy and feasibility of the method. The relative correction factors of ephedrine hydrochloride, protocatechuic acid, 5-caffeoylquinic acid, 4-hydroxybenzoic acid, neohesperidin, glycyrrhizic acid, and praeruptorin A with naringin as reference were 0.846, 0.582, 0.608, 0.293, 0.913, 2.207, and 0.940, respectively, which presented excellent reproducibility under different experimental conditions. Furthermore, QAMS and ESM showed no significant difference in the results for 15 batches of samples. Except protocatechuic acid and 5-caffeoylquinic acid, other six compounds were the exclusive components of single medicinal materials. In addition, glycyrrhizic acid and praeruptorin A were identified in the Jizhi Syrup for the first time, filling up the blank of no component detected in Glycyrrhizae Radix et Rhizoma and Peucedani Radix. The method established in this study is convenient, efficient, specific, accurate, and reliable, which can comprehensively and effectively evaluate the quality of Jizhi Syrup to ensure the safety and efficacy of this drug in clinical application.

Computational methods to automate the initial interpretation of lower extremity arterial Doppler and duplex carotid ultrasound studies.

BACKGROUND: Lower extremity arterial Doppler (LEAD) and duplex carotid ultrasound studies are used for the initial evaluation of peripheral arterial disease and carotid stenosis. However, intra- and inter-laboratory variability exists between interpreters, and other interpreter responsibilities can delay the timeliness of the report. To address these deficits, we examined whether machine learning algorithms could be used to classify these Doppler ultrasound studies. METHODS: We developed a hierarchical deep learning model to classify aortoiliac, femoropopliteal, and trifurcation disease in LEAD ultrasound studies and a random forest machine learning algorithm to classify the amount of carotid stenosis from duplex carotid ultrasound studies using experienced physician interpretation in an active, credentialed vascular laboratory as the reference standard. Waveforms, pressures, flow velocities, and the presence of plaque were input into a hierarchal neural network. Artificial intelligence was developed to automate the interpretation of these LEAD and carotid duplex ultrasound studies. Statistical analysis was performed using the confusion matrix. RESULTS: We extracted 5761 LEAD ultrasound studies from 2015 to 2017 and 18,650 duplex carotid ultrasound studies from 2016 to 2018 from the Indiana University Health system. The results showed the ability of artificial intelligence algorithms and method, with 97.0% accuracy for predicting normal cases, 88.2% accuracy for aortoiliac disease, 90.1% accuracy for femoropopliteal disease, and 90.5% accuracy for trifurcation disease. For internal carotid artery stenosis, the accuracy was 99.2% for predicting 0% to 49% stenosis, 100% for predicting 50% to 69% stenosis, 100% for predicting >70% stenosis, and 100% for predicting occlusion. For common carotid artery stenosis, the accuracy was 99.9% for predicting 0% to 49% stenosis, 100% for predicting 50% to 99% stenosis, and 100% for predicting occlusion. CONCLUSIONS: The machine learning models using LEAD data, with the collected blood pressure and waveform data, and duplex carotid ultrasound data with the flow velocities and the presence of plaque, showed that novel machine learning models are reliable in differentiating normal from diseased arterial systems and accurate in classifying the extent of vascular disease.

Mesenchymal stem cells increase heme oxygenase 1-activated autophagy in treatment of acute liver failure.

In recent years, transplantation of mesenchymal stem cells (MSCs) has attracted much attention as a potential cell-based therapy for acute liver failure (ALF). As an inducible enzyme, heme oxygenase 1 (HO-1) has been reported to have cytoprotective, anti-apoptotic and immunoregulatory effects. Autophagy, a conserved catabolic process in cells, may be an important pathway for MSCs to treat ALF. In this study, we aimed to explore whether MSCs treat ALF by regulating autophagy and whether HO-1 was involved in the same pathway. Bone marrow-derived MSCs were isolated from Sprague-Dawley rats and cultured according to an established protocol. Co-culture systems of MSCs and hepatocytes were used to assess autophagy in the treatment of ALF. Meanwhile, MSCs were transplanted into rats with d-galactosamine (Gal)-induced ALF. Autophagy inhibitor (3-methyladenine, 3-MA), HO-1 inhibitor (zinc protoporphyrin, ZnPP) and PI3K specific inhibitor (LY294002) were employed in the study. Blood samples and liver tissues were collected before euthanasia. Survival rate, liver function, inflammatory factors, histology, Ki67 and TUNEL staining were determined. MSCs transplantation alleviated ALF both in vivo and in vitro. Autophagy and autophagy-related proteins were significantly up-regulated during MSCs treatment. 3-MA attenuated the therapeutic effect of MSCs. Administration of LY294002 before ALF induction inhibited hepatocyte autophagy. During the MSCs treatment, the HO-1 expression was increased, while inhibiting HO-1 attenuated the therapeutic effect of MSCs as well as hepatocyte autophagy. These findings suggested MSCs could alleviate ALF by increasing the HO-1 expression, which played an important role in activating autophagy through PI3K/AKT signaling pathway.

[Relationship between Autophagy and Curcumin-induced Anticancer Effect].

Curcumin is a polyphenol extracted from turmeric rhizome and has multiple pharmacological roles. Recently,its anticancer properties have been recognized. Also,curcumin regulates autophagy in tumor cells via signaling pathways including AMP-activated protein kinase,mammalian target of rapamycin,transcription factor EB,Beclin-1,B-cell lymphoma 2,and endoplasmic reticulum stress. Considering the complicated crosstalk between autophagy and apoptosis,in this article we summaize the mechanism of curcumin-induced autophagy and its effect on apoptosis,with an attempt to provide insights on tumor therapy.

[Effects of Pogostemon cablin on gastrointestinal function of rats with syndrome of damp retention in middle-jiao].

To investigate the effects of Pogostemon cablin(patchouli) on gastrointestinal function of rats with the syndrome of damp retention in middle-jiao, and explore its therapeutic mechanism. In this study, gastrointestinal function of rats with the syndrome of damp retention in middle-jiao was evaluated by multiple assays including gastric remnant rate, small intestine propelling rate, gastric juice quantity, pepsin activity and gastrointestinal tissue morphology. ELISA was used to detect gastrointestinal hormones including MTL, GAS, VIP and cytokines including TNF-α and interleukin 10 in rat serum. Real-time fluorescent quantitative PCR technique was used to detect relative mRNA expression of AQP3, AQP4 and AQP8 in gastric and colonic tissues to explore the mechanism of P. cablin in treatment of gastrointestinal functions. The results showed that middle and high dose of P. cablin (3.24, 6.48 g•kg⁻¹) could obviously decrease the gastric remnant rate, promote gastric emptying, increase the small intestine propelling rate(P<0.05), speed up the propulsive movement of gastrointestinal tract, increase the secretion and acidity of gastric juice, increase the activity of pepsin, and improve the injury of gastrointestinal tissue. All the doses of P. cablin could increase the concentration of MTL and GAS in serum, reduce the concentration of VIP, TNF-α and IL-10 in serum, decrease the mRNA expression of AQP3 in gastric and colonic tissues, and increase the expression levels of AQP4 and AQP8 in colonic tissues. The regulatory effects were better in middle and high dose groups. In conclusion, regulation of the levels of gastrointestinal hormones, inflammatory cytokines and aquaporins may be the paths for P. cablin to maintain normal gastrointestinal function of rats with the syndrome of damp retention in middle-jiao. The results of the study laid a foundation for clarifying the treatment mechanism of aromatic damp-resolving drugs for indications including damp retention in middle-jiao and transformation failure of spleen.

Correlation between body mass index and lymph node metastasis in papillary thyroid carcinoma: a retrospective clinical study.

Background: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland, with lymph node metastasis significantly affecting patient prognosis. In recent years, body mass index (BMI) has garnered widespread attention as a potential factor influencing cancer development. This study aimed to explore the relationship between BMI and lymph node metastasis in patients with PTC, particularly focusing on the risk of metastasis in the lateral and central neck compartments. Methods: This retrospective study comprised 993 patients who underwent surgical treatment and were pathologically confirmed to have PTC. Patient BMI data were collected, and their relationship with lymph node metastasis in the lateral and central neck compartments was analyzed. Logistic regression models were employed to analyze the correlation between BMI and lymph node metastasis. Results: The study found a significant correlation between BMI and the risk of lateral neck lymph node metastasis in patients (P=0.008), along with a corresponding increase in extrathyroidal extension risk (P=0.02). While elevated BMI did not directly increase the risk of central compartment metastasis, a significant increase was observed in the number of central compartment lymph node metastases (P=0.009) and their proportion among the total central compartment lymph nodes (P=0.01) in patients with higher BMI. Additionally, multifocality, age, and gender were identified as risk factors for lateral neck lymph node metastasis, whereas Hashimoto's thyroiditis did not exhibit a similar impact. Conclusions: This study highlights that higher BMI is an important risk factor for lateral neck lymph node metastasis in patients with PTC and may exacerbate the severity of central compartment lymph node metastasis. These findings underscore the importance of considering BMI in the management of thyroid cancer and provide data support for future prevention and intervention strategies.

A "Mesh Scaffold" that regulates the mechanical properties and restricts the phase transition-induced volume change of the PNIPAM-based hydrogel for wearable sensors.

Poly(N-isopropylacrylamide) (PNIPAM) is capable of improving the reversibility and responsiveness of flexible electronics. However, its phase transition-induced volume variation and poor adhesiveness remain limitations for expending its applications. Herein, a pressure-sensitive adhesive (PSA), which is a type of mesh scaffold, is constructed inside the network of PNIPAM, providing the hydrogel with a constant volume in response to different temperatures, in situ tunable mechanical properties, and superior adhesiveness. The reversible density of the mesh scaffold adjusts the aggregation state of the hydrogel chains, whereupon it is capable of changing its mechanical modulus from 6.7 kPa to 45.3 kPa. This mechanical mechanism contributes to hydrogel-based flexible devices for multiple applications, especially in pressure-related sensors. The mesh scaffold restricts the phase-transition-induced volume variation, which allows the hydrogel sensor to stably monitor the external pressure at various temperatures. The high adhesion enables the effective interfacial interaction with the skin, avoiding the loss of sensing signals during the detection of human body movements. When it is assembled into an electronic device, it can transmit information and recognize sign language via Morse code. Thus, herein, we report a hydrogel sensor that is promising for pressure detection in temperature-unstable environments, especially for managing the health of patients who require emergency medical care through sign language recognition.

Mesenchymal stem cells alleviate autoimmune thyroiditis by modulating macrophage phenotypes and through influencing the STING pathway.

BACKGROUND: Hashimoto's thyroiditis is a chronic autoimmune inflammatory disease with a high prevalence and currently lacks effective treatment options. Previous preclinical and clinical trials have established mesenchymal stem cells (MSCs) as a promising therapeutic approach; however, there is limited research on MSC treatment for Hashimoto's thyroiditis, and the underlying molecular mechanisms remain unclear. METHODS: MSCs isolated from 4 to 6-week-old Lewis rats were employed for thyroiditis treatment. The efficacy of MSCs was assessed through histological and serological parameters. Molecular mechanisms of MSC therapy for Hashimoto's thyroiditis were explored by examining macrophage presence within thyroid tissue and relevant pathways. RESULTS: In this study, we observed elevated oxidative stress and endoplasmic reticulum stress within the thyroid tissue of Hashimoto's thyroiditis patients, and MSC therapy effectively mitigated this process. Furthermore, we found that the therapeutic potential of MSCs in the EAT model depended on the STING pathway. MSCs reduced endoplasmic reticulum stress and inflammasome levels within the thyroid tissue by modulating the STING pathway. Additionally, MSCs inhibited the expression of IRE1α in thyroid tissue macrophages, thereby reducing the polarization of M1-type macrophages CONCLUSIONS: The STING pathway appears to be a crucial mechanism by which MSCs modulate macrophage polarization in thyroid tissue, offering a potential treatment for thyroiditis.

Antidehydration and Stable Mechanical Properties during the Phase Transition of the PNIPAM-Based Hydrogel for Body-Temperature-Monitoring Sensors.

Poly(N-isopropylacrylamide) (PNIPAM) enhances the reversibility and responsiveness of wearable temperature-sensitive devices. However, an open question is whether and how the hydrogel design can prevent adhesive performance loss caused by phase-transition-induced dehydration and unstable mechanical properties between devices and human skin and reduce interfacial failure. Herein, a gelatin-mesh scaffold-based hydrogel (NAGP-Gel) is constructed to inhibit dehydration and volume change, leading to stable mechanical properties, superior adhesiveness, and thermal sensing sensitivity during the phase transition. NAGP-Gel enhances the polymer chains-water interaction and weakens the degree of aggregation of polymer chains-chains, improving antidehydration properties under 45 °C conditions that are higher than the lower critical solution temperature (LCST; i.e., ∼32 °C). The mesh scaffold greatly restricts the phase-transition-induced polymer chain movement and maintains the mechanical performance. In a 60 °C environment, the maximum water loss and volume retention ratio of NAGP-Gel are only 3.58% and 97.3%, respectively. Additionally, NAGP-Gel serves as a temperature sensor, producing a stable thermal-electrical signal within the LCST range. It also can be assembled into an electronic device enabling the transmission of information and recognition of sign language via Morse code. This work broadens the application of PNIPAM in constructing intelligent hydrogels and opens the door to exploring emerging hydrogels for temperature-monitoring applications.

Impedance Sliding-Mode Control Based on Stiffness Scheduling for Rehabilitation Robot Systems.

Rehabilitation robots can reproduce the rehabilitation movements of therapists by designed rehabilitation robot control methods to achieve the goal of training the patients' motion abilities. This paper proposes an impedance sliding-mode control method based on stiffness-scheduled law for the rehabilitation robot, which can be applied to rehabilitation training with both active and passive modes. A free-model-based sliding-mode control strategy is developed to avoid model dependence and reduce the system uncertainty caused by limb shaking. Additionally, the stiffness scheduling rule automatically regulates the impedance parameter of the rehabilitation robot based on the force exerted by the patient on the robot such that the rehabilitation training caters to the patient's health condition. The proposed method is compared with the fixed stiffness and variable stiffness impedance methods, and the superiority of the proposed method is proved. Rehabilitation training experiments on an actual rehabilitation robot are provided to demonstrate the feasibility and stability of the proposed method.

Manganese-facilitated dynamic active-site generation on Ni2P with self-termination of surface reconstruction for urea oxidation at high current density.

Electrochemical urea oxidation reaction (UOR) suffers from sluggish reaction kinetics due to its complex 6-electron transfer processes combined with conversion of complicated intermediates, severely retarding the overall energy conversion efficiency. Herein, manganese-doped nickel phosphide nanosheets (Mn-Ni2P) are constructed and employed for driving UOR. Comprehensive analysis deciphers that Mn doping could efficiently accelerate the surface reconstruction of Mn-Ni2P electrode, generating highly reactive NiOOH-MnOOH heterostructure with local nucleophilic and electrophilic regions. Such unique structure could accelerate the targeted adsorption and activation of C and N atoms, promoting fracture of CN bond in urea. In addition, moderate Mn doping could efficiently enhance the adsorption capacities of urea molecules and some key intermediates, and minish the energy barrier for *CO2 desorption, accelerating refreshing of the catalyst. Consequently, the Mn-Ni2P electrode exhibits excellent UOR catalytic activity, achieving an industrial-level current density of 1000 mA cm-2 at 1.46 V (vs. RHE).

Toll-like receptors in health and disease.

Toll-like receptors (TLRs) are inflammatory triggers and belong to a family of pattern recognition receptors (PRRs) that are central to the regulation of host protective adaptive immune responses. Activation of TLRs in innate immune myeloid cells directs lymphocytes to produce the most appropriate effector responses to eliminate infection and maintain homeostasis of the body's internal environment. Inappropriate TLR stimulation can lead to the development of general autoimmune diseases as well as chronic and acute inflammation, and even cancer. Therefore, TLRs are expected to be targets for therapeutic treatment of inflammation-related diseases, autoimmune diseases, microbial infections, and human cancers. This review summarizes the recent discoveries in the molecular and structural biology of TLRs. The role of different TLR signaling pathways in inflammatory diseases, autoimmune diseases such as diabetes, cardiovascular diseases, respiratory diseases, digestive diseases, and even cancers (oral, gastric, breast, colorectal) is highlighted and summarizes new drugs and related clinical treatments in clinical trials, providing an overview of the potential and prospects of TLRs for the treatment of TLR-related diseases.

Exosomal microRNA let-7c-5p enhances cell malignant characteristics by inhibiting TAGLN in oral cancer.

Background: Oral cancer, a malignancy that is prevalent worldwide, is often diagnosed at an advanced stage. MicroRNAs (miRNAs) in circulating exosomes have emerged as promising cancer biomarkers. The role of miRNA let-7c-5p in oral cancer remains underexplored, and its potential involvement in tumorigenesis warrants comprehensive investigation. Methods: Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content. Isolation of the exosomes was confirmed through transmission electron microscopy. Quantitative PCR was used to assess the miRNA profiles. The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability, migration, and invasion were analyzed via CCK-8 and Transwell assays. Moreover, we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes. Results: let-7c-5p was upregulated in serum-derived exosomes of patients with oral cancer. Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative, migratory, and invasive capacities, and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness. Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes. We further identified TAGLN as a direct target of let-7c-5p, which has been implicated in modulating the oncogenic potential of oral cancer cells. Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells. Conclusion: Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression, highlighting its potential as a diagnostic and therapeutic strategy.