Stable Cycling of All-Solid-State Lithium Batteries Enabled by Cyano-Molecular Diamond Improved Polymer Electrolytes.

The interfacial instability of the poly(ethylene oxide) (PEO)-based electrolytes impedes the long-term cycling and further application of all-solid-state lithium metal batteries. In this work, we have shown an effective additive 1-adamantanecarbonitrile, which contributes to the excellent performance of the poly(ethylene oxide)-based electrolytes. Owing to the strong interaction of the 1-Adamantanecarbonitrile to the polymer matrix and anions, the coordination of the Li+-EO is weakened, and the binding effect of anions is strengthened, thereby improving the Li+ conductivity and the electrochemical stability. The diamond building block on the surface of the lithium anode can suppress the growth of lithium dendrites. Importantly, the 1-Adamantanecarbonitrile also regulates the formation of LiF in the solid electrolyte interface and cathode electrolyte interface, which contributes to the interfacial stability (especially at high voltages) and protects the electrodes, enabling all-solid-state batteries to cycle at high voltages for long periods of time. Therefore, the Li/Li symmetric cell undergoes long-term lithium plating/stripping for more than 2000 h. 1-Adamantanecarbonitrile-poly(ethylene oxide)-based LFP/Li and 4.3 V Ni0.8Mn0.1Co0.1O2/Li all-solid-state batteries achieved stable cycles for 1000 times, with capacity retention rates reaching 85% and 80%, respectively.

Direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension patients: A retrospective cohort study.

INTRODUCTION: Direct oral anticoagulants (DOACs) are increasingly prescribed for life-long anticoagulation in chronic thromboembolic pulmonary hypertension (CTEPH) patients, despite not being recommended in the guidelines. This study aims to evaluate the efficacy and safety of DOACs in CTEPH patients. METHODS: From May 2013 to December 2022, patients who were first diagnosed with CTEPH in Fuwai Hospital and started long-term anticoagulation treatment with warfarin or DOACs were retrospectively included and followed up until (1) death, (2) transition to other kinds of anticoagulants, or (3) discontinuation of anticoagulation. Propensity score matching was used to balance confounding bias of baseline characteristics. All-cause death, major bleeding, clinically relevant nonmajor bleeding and venous thromboembolism (VTE) recurrence were obtained and analysed. RESULTS: After propensity score matching, 115 patients taking warfarin and 206 patients taking DOACs were included in our study and followed up for 5.5 [3.4, 7.1] years. There was no significant difference of survival between the warfarin and the DOAC group (p = 0.77). The exposure adjusted event rate of major bleeding (0.3 %/person-year vs 0.4 %/person-year, p = 0.705) and clinically relevant nonmajor bleeding (3.1 %/person-year vs 3.2 %/person-year, p > 0.999) was similar between two groups. The exposure adjusted rate of VTE recurrence was significantly higher in the DOAC group (1.5 %/person-year vs 0.3 %/person-year, p = 0.030). CONCLUSION: In anticoagulation of CTEPH patients, DOACs have similar survival rate, similar risk of bleeding but higher risk of VTE recurrence than warfarin.

Diarylheptanoid glycosides from Dioscorea nipponica rhizomes.

A group of previously undescribed diarylheptanoids with mono/di-glucose substitution, diodiarylheptosides A-F (1-6), together with six known diarylheptanoids (7-12) were isolated from the rhizomes of Dioscorea nipponica. Their structures were established by comprehensive UV, IR, HR-ESI-MS and NMR analyses, and their absolute configurations were determined by a comparison of calculated and experimental ECD, some with optical rotations, after acid-hydrolysis. Moreover, bioassay results showed that compounds 3 and 11 exhibited stronger NO inhibitions on lipopolysaccharides-induced RAW 264.7 cells, with the IC50 values of 14.91 ± 0.62 and 12.78 ± 1.12 µM.

Structural basis of tolvaptan binding to the vasopressin V2 receptor.

The vasopressin V2 receptor (V2R) is a validated therapeutic target for autosomal dominant polycystic kidney disease (ADPKD), with tolvaptan being the first FDA-approved antagonist. Herein, we used Gaussian accelerated molecular dynamics simulations to investigate the spontaneous binding of tolvaptan to both active and inactive V2R conformations at the atomic-level. Overall, the binding process consists of two stages. Tolvaptan binds initially to extracellular loops 2 and 3 (ECL2/3) before overcoming an energy barrier to enter the pocket. Our simulations result highlighted key residues (e.g., R181, Y205, F287, F178) involved in this process, which were experimentally confirmed by site-directed mutagenesis. This work provides structural insights into tolvaptan-V2R interactions, potentially aiding the design of novel antagonists for V2R and other G protein-coupled receptors.

How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's dis-ease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disas-sembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find as-sembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by the disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

Cervical extracellular matrix hydrogel optimizes tumor heterogeneity of cervical squamous cell carcinoma organoids.

Cervical cancer, primarily squamous cell carcinoma, is the most prevalent gynecologic malignancy. Organoids can mimic tumor development in vitro, but current Matrigel inaccurately replicates the tissue-specific microenvironment. This limitation compromises the accurate representation of tumor heterogeneity. We collected para-cancerous cervical tissues from patients diagnosed with cervical squamous cell carcinoma (CSCC) and prepared uterine cervix extracellular matrix (UCEM) hydrogels. Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase-AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor κB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.

Floating MIL-88A(Fe)@expanded perlites catalyst for continuous photo-Fenton degradation toward tetracyclines under artificial light and real solar light.

In this work, MIL-88A(Fe) was immobilized onto the expanded perlites to fabricate the floating MIL-88A(Fe)@expanded perlites (M@EP) catalyst via high throughput batch synthesis method under room temperature. The as-prepared M@EP could efficiently activate H2O2 to achieve 100% tetracycline antibiotics (TCs) removal under both artificial low power UV light (UVL) and real sunlight (SL) irradiation. The toxicological evaluation, growth experiment of mung beans and antimicrobial estimation revealed the decreasing aquatic toxicity of the TCs intermediates compared to those of the pristine TCs. A self-designed continuous bed reactor was employed to investigate the long-term operation of the M@EP. The findings demonstrated that the antibiotics mixture can be continuously degraded up to 7 days under UVL and 5 daytimes under SL irradiation, respectively. More importantly, ca. 76.9% and 81.6% of total organic carbon (TOC) removal efficiencies were accomplished in continuous bed reactor under UVL and SL irradiation, respectively. This work advances the immobilized MOFs on floating supports for their practical application in large-scale wastewater purification through advanced oxidation processes. ENVIRONMENTAL IMPLICATION: This work presented the high throughput production and photo-Fenton degradation application of floating MIL-88A(Fe)@expanded perlites (M@EP). Three tetracycline antibiotics (TCs) were selected as model pollutants to test the degradation ability of M@EP in batch experiment and continuous operation under artificial light and solar light. The complete TCs degradation could be accomplished in self-designed device up to 7 d under UV light and 5 d under real solar light. This work tapped a new door to push MOFs-based functional materials in the real water purification.

Associations between dietary macronutrient quality and asthenozoospermia risk: a hospital-based case-control study.

Background & aims: Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and asthenozoospermia risk have not been reported to date. Thus, this study aimed to be the first to explore the associations between macronutrient quality and asthenozoospermia risk using the novel multidimensional macronutrient quality index (MQI). Methods: A case-control study was conducted at infertility clinics of Shengjing Hospital of China Medical University during June and December 2020, including 552 asthenozoospermia cases and 585 normozoospermia controls. Data on diet were collected using a validated food frequency questionnaire. MQI was estimated according to the carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Binary logistic regression models were performed to calculate the odds ratio (OR) with a 95% confidence interval (CI). Subgroup and interaction analyses were performed based on age, body mass index, physical activity, smoking, drinking, and education level. Dose-response relationships were evaluated by restricted cubic splines. Sensitivity analyses were performed in two ways. First, participants with a dietary change were excluded to lower potential reverse causation. Then, we used the healthy plate protein source quality index instead of PQI to redefine MQI. Results: No statistically significant association was observed between dietary MQI and asthenozoospermia risk (OR = 1.24, 95% CI: 0.88-1.73). The sub-indices of MQI, CQI, FQI, and PQI, failed to be identified as having a statistically significant association with asthenozoospermia risk (OR = 1.35, 95% CI: 0.92-1.97 for CQI; OR = 1.13, 95% CI: 0.84-1.53 for FQI; OR = 1.28, 95% CI: 0.92-1.78 for PQI). However, CQI showed a positive association with the risk of asthenozoospermia among non-drinkers (Ptrend < 0.05) and highly educated participants (OR = 1.82, 95% CI: 1.13-2.94; Ptrend < 0.05). Additionally, there was a multiplicative interaction between CQI and education level for asthenozoospermia risk (P < 0.05). Conclusions: Our findings demonstrated no association of MQI and its sub-indices with asthenozoospermia risk except for CQI. Although our findings are mostly non-significant, they contribute novel knowledge to this research field and lay the foundation for future studies.

How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's disease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disassembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find assembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

Antimicrobial peptide cecropin B functions in pathogen resistance of Mythimna separata.

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.

Evaluation of the inhibitory effects of antigout drugs on human carboxylesterases in vitro.

Gout is an immune-metabolic disease that frequently coexists with multiple comorbidities such as chronic kidney disease, cardiovascular disease and metabolic syndrome, therefore, it is often treated in combination with these complications. The present study aimed to evaluate the inhibitory effect of antigout drugs (allopurinol, febuxostat, topiroxostat, benzbromarone, lesinurad and probenecid) on the activity of the crucial phase I drug-metabolizing enzymes, carboxylesterases (CESs). 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) were utilized as the probe reactions to determine the activity of CES1 and CES2, respectively, through in vitro culturing with human liver microsomes. Benzbromarone and lesinurad exhibited strong inhibition towards CESs with Ki values of 2.16 and 5.15 µM for benzbromarone towards CES1 and CES2, respectively, and 2.94 µM for lesinurad towards CES2. In vitro-in vivo extrapolation (IVIVE) indicated that benzbromarone and lesinurad might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CESs. In silico docking showed that hydrogen bonds and hydrophobic interactions contributed to the intermolecular interactions of antigout drugs on CESs. Therefore, vigilant monitoring of potential drug-drug interactions (DDIs) is imperative when co-administering antigout drugs in clinical practice.

A bibliometric study on trends in chiropractic research from 1920 to 2023.

OBJECTIVE: An increasing body of evidence suggests a positive role of chiropractic in the treatment of neuro-musculoskeletal disorders. This study aims to explore current research hotspots and trends, providing insights into the broad prospects of this field. METHODS: A bibliometric review was conducted on all chiropractic articles included in the Web of Science Core Collection before December 31, 2023. RESULTS: Over the past century, the volume of research in the field of chiropractic has been fluctuating annually, with four peaks observed in total. The United States, Canada, Australia, and the United Kingdom are leading countries. Chu, Eric Chun-Pu is the author with the most publications, while Bronfort, Gert has the highest total citation count. The University of Southern Denmark has produced the most publications, while Queens University - Canada is the most central institution. The Journal of Manipulative and Physiological Therapeutics is the journal with the most publications and citations, while the Journal of the American Medical Association is the most central journal. The two most-cited articles were both authored by Eisenberg DM. Emerging keywords include "chronic pain" and "skills". The theoretical mechanisms and scientific basis of chiropractic, its clinical practice and safety, education and training, integration with other disciplines, and patient experiences and satisfaction are the frontiers and hotspots of research. CONCLUSION: This study integrates bibliometric analysis to summarize the current state of research and global network centers in the field of chiropractic, further highlighting the hotspots and trends in this field. However, Individual and national rankings should be interpreted with caution due to our focus on Web of Science rather than PubMed.

Use of 3D echocardiography facilitates analysis of thrombolytic efficacy in patients with persistent atrial fibrillation.

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation (AF). During follow-up after 9 to 24 weeks of Rivaroxaban treatment, patients were divided into 'effective group' (n = 143) and 'ineffective group' (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAADmean), angle between left atrial appendage and left atrial (LAA-A), velocity of blood flow in left atrial appendage (LAA-v) and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF and LAA-v values were greater and LAD and LAADmean values were lower in the effective (P<0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A and LAA-v with anticoagulant efficacy (P<0.05). The efficacy of Rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A and LAA-v. Multivariate logistic regression analysis further revealed LAEF (OR 1.7, 95% CI 0.45-16.9, P=0.008), 3D-EF (OR 6.4, 95% CI 1.06-16.9, P=0.039), and left ventricular global longitudinal strain (GLS) (OR 18.0, 95% CI 1.38-35.68, P=0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of Rivaroxaban as an anticoagulation agent.

Space-Confined Growth of Ultrathin P-Type GeTe Nanosheets for Broadband Photodetectors.

As p-type phase-change degenerate semiconductors, crystalline and amorphous germanium telluride (GeTe) exhibit metallic and semiconducting properties, respectively. However, the massive structural defects and strong interface scattering in amorphous GeTe films significantly reduce their performance. In this work, two-dimensional (2D) p-type GeTe nanosheets are synthesized via a specially designed space-confined chemical vapor deposition (CVD) method, with the thickness of the GeTe nanosheets reduced to 1.9 nm. The space-confined CVD method improves the crystallinity of ultrathin GeTe by lowering the partial pressure of the reactant gas, resulting in GeTe nanosheets with excellent p-type semiconductor properties, such as a satisfactory on/off ratio of 105 . Temperature-dependent electrical measurements demonstrate that variable-range hopping and optical-phonon-assisted hopping mechanisms dominate transport behavior at low and high temperatures, respectively. GeTe devices exhibit significantly high responsivity (6589 and 2.2 A W-1 at 633 and 980 nm, respectively) and detectivity (1.67 × 1011 and 1.3 × 108 Jones at 633 and 980 nm, respectively), making them feasible for broadband photodetectors in the visible to near-infrared range. Furthermore, the fabricated GeTe/WS2 diode exhibits a rectification ratio of 103 at zero gate voltage. These satisfactory p-type semiconductor properties demonstrate that ultrathin GeTe exhibits enormous potential for applications in optoelectronic interconnection circuits.

Electroacupuncture promotes macrophage/microglial M2 polarization and suppresses inflammatory pain through AMPK.

Inflammatory pain, the most prevalent disease globally, remains challenging to manage. Electroacupuncture emerges as an effective therapy, yet its underlying mechanisms are not fully understood. This study investigates whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-regulated silent information regulator 1 (SIRT1) contributes to electroacupuncture's antinociceptive effects by modulating macrophage/microglial polarization in the spinal dorsal horn of a mouse model of inflammatory pain. In this study, mice, introduced to inflammatory pain through subcutaneous injections of complete freund's adjuvant (CFA) in the plantar area, underwent electroacupuncture therapy every alternate day for 30-min sessions. The assessment of mechanical allodynia and thermal hyperalgesia in these subjects was carried out using paw withdrawal frequency and paw withdrawal latency measurements, respectively. Western blot analysis measured levels of AMPK, phosphorylation-adenosine 5'-monophosphate (AMP)-activated protein kinase, SIRT1, inducible nitric oxide synthase, cluster of differentiation 86, arginase 1, and interleukin 10. In contrast to the group treated solely with CFA, the cohort receiving both CFA and electroacupuncture demonstrated notable decreases in both thermal hyperalgesia and mechanical allodynia. This was accompanied by a marked enhancement in AMPK phosphorylation levels. AMPK knockdown reversed electroacupuncture's analgesic effects and reduced M2 macrophage/microglial polarization enhancement. Additionally, AMPK knockdown significantly weakened electroacupuncture-induced SIRT1 upregulation, and EX-527 injection attenuated electroacupuncture's facilitation of M2 macrophage/microglial polarization without affecting AMPK phosphorylation levels. Furthermore, combining electroacupuncture with SRT1720 enhanced the analgesic effect of SRT1720. Our findings suggest that AMPK regulation of SIRT1 plays a critical role in electroacupuncture's antinociceptive effect through the promotion of M2 macrophage/microglial polarization.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Investigating the Effect of Microwave Induction on the Polymerization Rate of Polycarboxylate Superplasticizers.

As a transmission medium and heating energy, microwave is widely favored due to its high efficiency, strong selectivity, and easy control. Here, the effects of different heating methods (conventional thermal induction (CI) and microwave induction (MI)) on the polymerization rate of polycarboxylate superplasticizer (PCE) were investigated. Compared with CI, MI significantly boosted the polymerization rate (by approximately 51 times) and markedly decreased the activation energy (Ea), from 46.83 kJ mol-1 to 35.07 kJ mol-1. The polar of the monomers and initiators in the PCE synthesis contributes to varying permittivities and loss factors under the microwave field, which are influenced by their concentration and reaction temperature. The insights gained from the microwave thermal effects and the micro-kinetics of the PCE polymerization system are able to propose theoretical underpinnings for the industrial-scale application of microwave induction polymerization, potentially steering the synthesis of polymer materials towards a more efficient and cleaner process.

Schisandrin B promotes hepatic differentiation from human umbilical cord mesenchymal stem cells.

Human umbilical cord mesenchymal stem cells (UC-MSCs)-derived hepatocyte-like cells (HLCs) have shown great promise in the treatment of liver diseases. However, most current induction protocols yield hepatocyte-like cells with limited function as compared with primary hepatocytes. Schisandrin B (Sch B) is one of the main components of Schisandra chinensis, which can prevent fibrosis progression and promote liver cell regeneration. Herein, we investigated the effects of Sch B on hepatic differentiation of UC-MSCs. We found that treatment with 10 µM Sch B from the second stage of the differentiation process increased hepatic marker levels and hepatic function. Additionally, RNA-seq analysis revealed that Sch B promoted hepatic differentiation via activating the JAK2/STAT3 pathway. When transplanted HLCs into mice with CCL4-induced liver fibrosis, Sch B-treated HLCs exhibited significant therapeutic effects. This study provides an optimized hepatic differentiation protocol for UC-MSCs based on Sch B, yielding functioning cells for liver disease treatment.

Opportunities and Perspectives for Three Dimensional Culture of Mesenchymal Stem Cell-Derived Exosomes.

Exosomes are nanosized extracellular vesicles (EVs) that participate in intercellular communication through surface proteins and the delivery of internal cargo. The exosomes have gained attention for their potential as disease biomarkers and therapeutic agents. The therapeutic ability of exosomes has been verified by copious previous studies. Effective methods for extensive clinical applications are being researched for exosome-based regenerative therapies, including the application of 3D cultures to enhance exosome production and secretion, which can resolve limited exosome secretion from the parent cells. Cell culture has emerged as a crucial approach for biomedical research because of its many benefits. Both well-established continuous cell lines and primary cell cultures continue to be invaluable for basic research and clinical application. Previous studies have shown that three-dimensional cultured exosomes (3D-Exo) improve therapeutic properties and yields compared with traditional culture systems. Since the majority of studies have focused on exosomes derived from mesenchymal stem cells (MSC-Exo), this review will also concentrate on MSC-Exo. In this review, we will summarize the advantages of 3D-Exo and introduce the 3D culture system and methods of exosome isolation, providing scientific strategies for the diagnosis, treatment, and prognosis of a wide variety of diseases.