Theoretical study on the role of magnesium chloride complexes induced by different magnesium-to-chlorine ratios in magnesium-sulfur batteries.

In magnesium-sulfur batteries, electrolyte exploration is vital for developing high-energy-density, safe, and reliable batteries. This study focused on cyclic THF and chain DME, representative solvents in ether electrolytes. MgCl2, an ideal anionic salt, forms mono-nuclear (MgCl2(DME)2), bi-nuclear ([Mg2(µ-Cl)2(DME)4]2+), and tri-nuclear ([Mg3(µ-Cl)4(DME)5]2+) complexes in DME. With increasing salt concentration, these complexes sequentially form. Under lower salt concentrations, THF and MgCl2 form mono-nuclear complexes ([MgCl2(THF)4]) and continue to form bi-nuclear complexes ([Mg2(µ-Cl)3(THF)6]+). However, at higher salt concentrations, bi-nuclear complexes ([Mg2(µ-Cl)3(THF)6]+) directly form in THF. Comparing HOMO-LUMO values, [Mg(DME)3]2+ is easily oxidized. Energy gaps decrease with Cl- ion addition, enhancing solution conductivity. Ratios of Mg2+ and Cl- in S-reduction complexes differ, suggesting DME is better at a low Mg/Cl ratio, and THF at a high Mg/Cl ratio. This study contributes to understanding complexes and enhancing Mg-S battery performance.

Kdm6a-CNN1 axis orchestrates epigenetic control of trauma-induced spinal cord microvascular endothelial cell senescence to balance neuroinflammation for improved neurological repair.

Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory factors. Despite extensive investigations into vascular senescence associated with aging and degenerative diseases, the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress, particularly its involvement in senescence-induced inflammation, remain insufficiently elucidated. In this study, we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury (SCI). Lysine demethylase 6A (Kdm6a), commonly known as UTX, emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells (SCMECs). Upregulation of UTX induces senescence in SCMECs, leading to an amplified release of proinflammatory factors, specifically the senescence-associated secretory phenotype (SASP) components, thereby modulating the inflammatory microenvironment. Conversely, the deletion of UTX in endothelial cells shields SCMECs against senescence, mitigates the release of proinflammatory SASP factors, and promotes neurological functional recovery after SCI. UTX forms an epigenetic regulatory axis by binding to calponin 1 (CNN1), orchestrating trauma-induced SCMECs senescence and SASP secretion, thereby influencing neuroinflammation and neurological functional repair. Furthermore, local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion, reinstating a local regenerative microenvironment and enhancing functional repair after SCI. In conclusion, targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion, alleviate neuroinflammation, and provide a novel treatment strategy for SCI repair.

Transcranial ultrasound estimation of viscoelasticity and fluidity in brain tumors aided by transcranial shear waves.

Cerebral diseases, such as brain tumors, are intricately linked to the mechanical properties of brain tissues. Estimating the mechanical properties of brain tumors using transcranial ultrasound is a promising approach. However, the complexity of cranial features introduces challenges, such as ultrasound attenuation and interference from multidirectional transcranial shear waves induced by impact vibrations. To address these issues, this study proposes a transcranial ultrasound estimation method assisted by transcranial shear vibrations. Transcranial vibrations apply shear forces on the parietal bone, inducing unidirectional transcranial shear waves within brain tissue, as validated through simulations. Shear waves at different frequencies were captured via transcranial ultrasound, which were used to assess the viscoelasticity and fluidity of brain tumors. Transcranial experimental validations were conducted in 3D-printed models with tumor phantoms and ex vivo animal tumors. Vibration safety assessments were also performed. The results demonstrate that transcranial ultrasound can detect micron displacements induced by transcranial shear waves. In phantom and ex vivo animal experiments, speed distribution maps were employed to determine the size and location of one or two tumors enclosed in the skull model. The results revealed that the proposed approach could detect tumors with a minimum diameter of 0.8 cm and an inter-tumor distance of 0.8 cm. Notably, significant differences in viscoelasticity and fluidity between normal brain tissue and brain tumors were found (p<0.001). The maximum assessment errors for the elasticity, viscosity, and fluidity using transcranial ultrasound were 11.90%, 4.82%, and 0.73%, respectively, indicating that fluidity was more robust than viscoelasticity. The maximum accelerations of the skull were only 3.21 ms-2.

Salt Tolerance in Machilus faberi: Elucidating Growth and Physiological Adaptations to Saline Environments.

Adversity stress is the main environmental factor limiting plant growth and development, including salt and other stress factors. This study delves into the adaptability and salt tolerance mechanisms of Machilus faberi Hemsl, a species with potential for cultivation in salinized areas. We subjected the plants to various salt concentrations to observe their growth responses and to assess key physiological and biochemical indicators. The results revealed that under high salt concentrations (500 and 700 mmol-1/L), symptoms such as leaf yellowing, wilting, and eventual death were observed. Notably, plant height and shoot growth ceased on the 14th day of exposure. Chlorophyll content (a, b, total a + b, and the a/b ratio) initially increased but subsequently decreased under varying levels of salt stress. Similarly, the net photosynthetic rate, stomatal conductance, leaf water content, and root activity significantly declined under these conditions. Moreover, we observed an increase in malondialdehyde levels and relative conductivity, indicative of cellular damage and stress. The activity of superoxide dismutase and ascorbate peroxidase initially increased and then diminished with prolonged stress, whereas peroxidase activity consistently increased. Levels of proline and soluble protein exhibited an upward trend, contrasting with the fluctuating pattern of soluble sugars, which decreased initially but increased subsequently. In conclusion, M. faberi exhibits a degree of tolerance to salt stress, albeit with growth limitations when concentrations exceed 300 mmol-1/L. These results shed light on the plant's mechanisms of responding to salt stress and provide a theoretical foundation for its cultivation and application in salt-affected regions.

Risk Factors and Patient-Reported Outcomes in Chinese Women with Postpartum Diastasis Recti Abdominis: An Observational Study.

Purpose: Diastasis recti abdominis (DRA) is a condition in which the linea alba is stretched and widened, and the abdominal muscles are separated from each other. DRA typically occurs in pregnant and postpartum women. We aimed to determine the risk factors and patient-reported outcomes (PROs) of DRA in Chinese postpartum women. Methods: This observational study was conducted in Hangzhou Hospital of Traditional Chinese Medicine, and involved 534 women who filled out the following risk-factor and PRO questionnaires: SF-MPQ-2, SF-ICIQ, LDQ, EPDS, MBIS, HerQles, and SF-36 (all Chinese versions). The inter-recti distance was measured by palpation. Statistical analyses were performed using SPSS v25.0 software and the Mann-Whitney U-test, chi-square test, binary logistic regression analysis (for risk factors of DRA), and the Kendall and Spearman tests (for correlation analysis). Results: After childbirth, 78.1% (417/534) of the enrolled women had DRA. Abdominal surgery (P = 0.002), number of pregnancies (P = 0.035), parity (P = 0.012), number of births (P = 0.02), fetal birth weight (P = 0.014), and waist-to-hip ratio in the supine position (P = 0.045) significantly differed between the DRA and non-DRA groups. Caesarean delivery was an independent risk factor for DRA. The PROs were significantly worse in the DRA group than in the non-DRA group. Conclusion: Caesarean delivery was an independent risk factor for DRA. Women with DRA are more likely to have limited physical activity or function after childbirth, lower self-confidence, and a decreased quality of life.

Exploration of a Predictive Model for Keloid and Potential Therapeutic Drugs based on Immune Infiltration and Cuproptosis-Related Genes.

The aim of this study was to investigate the correlation between CRGs and immunoinfiltration in keloid, develop a predictive model for keloid occurrence, and explore potential therapeutic drugs. The microarray datasets (GSE7890 and GSE145725) were obtained from Gene Expression Omnibus database to identify the differentially expressed genes (DEGs) between keloid and non-keloid samples. Key genes were identified through immunoinfiltration analysis and DEGs, then analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, followed by the identification of protein-protein interaction networks, transcription factors, and miRNAs associated with key genes. Additionally, a logistic regression analysis was performed to develop a predictive model for keloid occurrence, and potential candidate drugs for keloid treatment were identified. Three key genes (FDX1, PDHB, DBT) were identified, showing involvement in acetyl-CoA biosynthesis, mitochondrial matrix, oxidoreductase activity, and the tricarboxylic acid cycle. Immune infiltration analysis suggested the involvement of B cells, Th1 cells, DCs, T helper cells, APC co-inhibition, and T cell co-inhibition in keloid. These genes were used to develop a logistic regression-based nomogram for predicting keloid occurrence with an AUC of 0.859 and good calibration.We identified 32 potential drug molecules and extracted the top 10 compounds based on their P-values, showing promise in targeting key genes and potentially effective against keloid. Our study identified some genes in keloid pathogenesis and potential therapeutic drugs. The predictive model enhance early diagnosis and management. Further research is needed to validate and explore clinical implications.

Extracellular vesicles from UTX-knockout endothelial cells boost neural stem cell differentiation in spinal cord injury.

BACKGROUND: Vascular endothelial cells are pivotal in the pathophysiological progression following spinal cord injury (SCI). The UTX (Ubiquitously Transcribed Tetratripeptide Repeat on Chromosome X) serves as a significant regulator of endothelial cell phenotype. The manipulation of endogenous neural stem cells (NSCs) offers a compelling strategy for the amelioration of SCI. METHODS: Two mouse models were used to investigate SCI: NSCs lineage-traced mice and mice with conditional UTX knockout (UTX KO) in endothelial cells. To study the effects of UTX KO on neural differentiation, we harvested extracellular vesicles (EVs) from both UTX KO spinal cord microvascular endothelial cells (SCMECs) and negative control SCMECs. These EVs were then employed to modulate the differentiation trajectory of endogenous NSCs in the SCI model. RESULTS: In our NSCs lineage-traced mice model of SCI, a marked decrease in neurogenesis was observed post-injury. Notably, NSCs in UTX KO SCMECs mice showed enhanced neuronal differentiation compared to controls. RNA sequencing and western blot analyses revealed an upregulation of L1 cell adhesion molecule (L1CAM), a gene associated with neurogenesis, in UTX KO SCMECs and their secreted EVs. This aligns with the observed promotion of neurogenesis in UTX KO conditions. In vivo administration of L1CAM-rich EVs from UTX KO SCMECs (KO EVs) to the mice significantly enhanced neural differentiation. Similarly, in vitro exposure of NSCs to KO EVs resulted in increased activation of the Akt signaling pathway, further promoting neural differentiation. Conversely, inhibiting Akt phosphorylation or knocking down L1CAM negated the beneficial effects of KO EVs on NSC neuronal differentiation. CONCLUSIONS: In conclusion, our findings substantiate that EVs derived from UTX KO SCMECs can act as facilitators of neural differentiation following SCI. This study not only elucidates a novel mechanism but also opens new horizons for therapeutic interventions in the treatment of SCI. Video Abstract.

Efficacy and Safety of Endoscopic Retrograde Cholangiopancreatography in Children of Pancreaticobiliary Maljunction Without Obvious Biliary Dilatation.

PURPOSE: There is no standard surgical approach for pancreaticobiliary maljunction (PBM) without congenital biliary dilatation (CBD). This study aimed to compare outcomes between therapeutic endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic hepaticojejunostomy (LH) for pediatric patients of PBM without obvious biliary dilatation (PBM-nonOBD). METHODS: We retrospectively reviewed demographic and clinical data of pediatric patients with PBM-nonOBD from 2015 to 2021. There were 33 patients in ERCP group and 35 patients in LH group. Primary outcomes included treatment efficiency, postoperative recovery, and postoperative complications. Univariate analysis was further used to explore prognostic factors for ERCP. RESULTS: The mean diameter of the common bile duct in LH group was larger than that in ERCP group (8.6 ± 1.3 mm vs. 6.9 ± 2.1 mm, p = 0.003), while there were no significant differences between the two groups in age, gender, clinical manifestations, complications, and other imaging findings. Compared with LH group, ERCP group had a shorter operation time and postoperative recovery time. The treatment effective rate of ERCP was inferior to that of LH (45.4 % vs. 85.7 %, p＜0.001). For postoperative adverse events, post-ERCP pancreatitis (15.1 %) was most common in the ERCP group. 30.3 % of patients eventually required LH. Intestinal obstruction (5.7 %), recurrent cholangitis (5.7 %), gastrointestinal bleeding (2.8 %), and anastomotic stenosis (2.8 %) were observed in LH group and 8.6 % of patients required a reoperation. A long common channel may be associated with poor prognosis after ERCP. CONCLUSIONS: ERCP is associated with less surgical trauma, shorter recovery time, and fewer serious complications than LH, while the treatment effective rate of ERCP is inferior to LH. The indications for endoscopic sphincterotomy and the timing of radical surgery need to be further explored. LEVEL OF EVIDENCE: Ⅲ STUDY TYPE: Retrospective Comparative Study.

Exosomes derived from CD271+CD56+ bone marrow mesenchymal stem cell subpopoulation identified by single-cell RNA sequencing promote axon regeneration after spinal cord injury.

Rationale: Spinal cord injury (SCI) results in neural tissue damage. However, the limited regenerative capacity of adult mammals' axons upon SCI leads to persistent neurological dysfunction. Thus, exploring the pathways that can enhance axon regeneration in injured spinal cord is of great significance. Methods: Through the utilization of single-cell RNA sequencing in this research, a distinct subpopulation of bone marrow mesenchymal stem cells (BMSCs) that exhibits the capacity to facilitate axon regeneration has been discovered. Subsequently, the CD271+CD56+ BMSCs subpopulation was isolated using flow cytometry, and the exosomes derived from this subpopulation (CD271+CD56+ BMSC-Exos) were extracted and incorporated into a hydrogel to create a sustained release system. The aim was to investigate the therapeutic effects of CD271+CD56+ BMSC-Exos and elucidate the underlying mechanisms involved in promoting axon regeneration and neural function recovery. Results: The findings indicate that CD271+CD56+ BMSC-Exos share similar physical and chemical properties with conventional exosomes. Importantly, in an SCI model, in situ implantation of CD271+CD56+ BMSC-Exos hydrogel resulted in increased expression of NF and synaptophysin, markers associated with axon regeneration and synapse formation, respectively. This intervention also contributed to improved neural function recovery. In vitro experiments demonstrated that CD271+CD56+ BMSC-Exos treatment significantly enhanced axon extension distance and increased the number of branches in dorsal root ganglion axons. Moreover, further investigation into the molecular mechanisms underlying CD271+CD56+ BMSC-Exos-mediated axon regeneration revealed the crucial involvement of the miR-431-3p/RGMA axis. Conclusion: In summary, the implantation of CD271+CD56+ BMSC-Exos hydrogel presents a promising and effective therapeutic approach for SCI.

Clutter filtering of angular domain data for contrast-free ultrafast microvascular imaging.

Objective. Contrast-free microvascular imaging is clinically valuable for the assessment of physiological status and the early diagnosis of diseases. Effective clutter filtering is essential for microvascular visualization without contrast enhancement. Singular value decomposition (SVD)-based spatiotemporal filter has been widely used to suppress clutter. However, clinical real-time imaging relies on short ensembles (dozens of frames), which limits the implementation of SVD filtering due to the large error of eigen-correlated estimations and high dependence on optimal threshold when used in such ensembles.Approach. To address the above challenges of imaging in short ensembles, two optimized filters of angular domain data are proposed in this paper: grouped angle SVD (GA-SVD) and angular-coherence-based higher-order SVD (AC-HOSVD). GA-SVD applies SVD to the concatenation of all angular data to improve clutter rejection performance in short ensembles, while AC-HOSVD applies HOSVD to the angular data tensor and utilizes angular coherence in addition to spatial and temporal features for filtering. Feasible threshold selection strategies in each feature space are provided. The clutter rejection performance of the proposed filters and SVD was evaluated with Doppler phantom andin vivostudies at different cases. Moreover, the robustness of the filters was explored under wrong singular value threshold estimation, and their computational complexity was studied.Main results. Qualitative and quantitative results indicated that GA-SVD and AC-HOSVD can effectively improve clutter rejection performance in short ensembles, especially AC-HOSVD. Notably, the proposed methods using 20 frames had similar image quality to SVD using 100 frames.In vivostudies showed that compared to SVD, GA-SVD increased the signal-to-noise-ratio (SNR) by 6.03 dB on average, and AC-HOSVD increased the SNR by 8.93 dB on average. Furthermore, AC-HOSVD remained better power Doppler image quality under non-optimal thresholds, followed by GA-SVD.Significance. The proposed filters can greatly enhance contrast-free microvascular visualization in short ensembles and have potential for different clinical translations due to the performance differences.

Inhibition of UTX/KDM6A improves recovery of spinal cord injury by attenuating BSCB permeability and macrophage infiltration through the MLCK/p-MLC pathway.

Spinal cord injury (SCI) can prompt an immediate disruption to the blood-spinal cord barrier (BSCB). Restoring the integrity of this barrier is vital for the recovery of neurological function post-SCI. The UTX protein, a histone demethylase, has been shown in previous research to promote vascular regeneration and neurological recovery in mice with SCI. However, it is unclear whether UTX knockout could facilitate the recovery of the BSCB by reducing its permeability. In this study, we systematically studied BSCB disruption and permeability at different time points after SCI and found that conditional UTX deletion in endothelial cells (ECs) can reduce BSCB permeability, decrease inflammatory cell infiltration and ROS production, and improve neurological function recovery after SCI. Subsequently, we used RNA sequencing and ChIP-qPCR to confirm that conditional UTX knockout in ECs can down-regulate expression of myosin light chain kinase (MLCK), which specifically mediates myosin light chain (MLC) phosphorylation and is involved in actin contraction, cell retraction, and tight junctions (TJs) protein integrity. Moreover, we found that MLCK overexpression can increase the ratio of p-MLC/MLC, further break TJs, and exacerbate BSCB deterioration. Overall, our findings indicate that UTX knockout could inhibit the MLCK/p-MLC pathway, resulting in decreased BSCB permeability, and ultimately promoting neurological recovery in mice. These results suggest that UTX is a promising new target for treating SCI.

Targeted Delivery of RGD-CD146+CD271+ Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Promotes Blood-Spinal Cord Barrier Repair after Spinal Cord Injury.

Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB), potentially exacerbating nerve damage and emphasizing the criticality of preserving the BSCB integrity during SCI treatment. This study explores an alternative therapeutic approach for SCI by identifying a subpopulation of exosomes with stable BSCB function and achieving a specific targeted delivery. Specific subpopulations of CD146+CD271+ umbilical cord mesenchymal stem cells (UCMSCs) were isolated, from which engineered exosomes (RGD-CD146+CD271+ UCMSC-Exos) with targeted neovascularization function were obtained through gene transfection. In vivo and in vitro experiments were performed to explore the targeting and therapeutic effects of RGD-CD146+CD271+ UCMSC-Exos and the potential mechanisms underlying BSCB stabilization and neural function recovery. The results demonstrated that RGD-CD146+CD271+ UCMSC-Exos exhibited physical and chemical properties similar to those of regular exosomes. Notably, following intranasal administration, RGD-CD146+CD271+ UCMSC-Exos exhibited enhanced aggregation at the SCI center and demonstrated the specific targeting of neovascular endothelial cells. In the SCI model, intranasal administration of RGD-CD146+CD271+ UCMSC-Exos reduced Evans blue dye leakage, increased tight junction protein expression, and improved neurological function recovery. In vitro testing revealed that RGD-CD146+CD271+ UCMSC-Exos treatment significantly reduced the permeability of bEnd.3 cells subjected to oxygen-glucose deprivation, thereby restoring the integrity of tight junctions. Moreover, further exploration of the molecular mechanism underlying BSCB stabilization by CD146+CD271+ UCMSC-Exos identified the crucial role of the miR-501-5p/MLCK axis in this process. In conclusion, targeted delivery of RGD-CD146+CD271+ UCMSC-Exos presents a promising and effective treatment option for SCI.

First-principles investigation on multi-magnesium sulfide and magnesium sulfide clusters in magnesium-sulfide batteries.

Because of the abundance of magnesium and sulfur and their low cost, the development of magnesium sulfur batteries is very promising. In particular, the battery performance of nanoscale (MgS)n clusters is much better than that of bulk sized MgS. However, the structures, stability, and properties of MgxSy and (MgS)n clusters, which are very important to improve the performance of Mg-S batteries, are still unexplored. Herein, the most stable structures of MgxSy (x = 1-8, y = 1-8) and (MgS)n (n = 1-10) are reliably determined using the structure search method and density functional theory to calculate. According to calculation results, MgS3 and Mg6S8 may not exist in the actual charging and discharging products of magnesium sulfide batteries. The (MgS)n (n ≥ 5) clusters exhibit intriguing cage-like structures, which are favorable for eliminating dangling bonds and enhancing structural stability. Compared to the MgS monomer, each sulfur atom in the clusters is coordinated with more magnesium atoms, thus lengthening the Mg-S bond length and decreasing the Mg-S bond activation energy. Notably, with the increase of dielectric constant of electrolyte solvent, compared to the DME (ε = 7.2), THF (ε = 7.6) and C2H4Cl2 (ε = 10.0), MgxSy and (MgS)n clusters are most stable in the environment of C3H6O (ε = 20.7). It can delay the transformation of magnesium polysulfide to the final product MgS, which is conducive to improving the performance of Mg-S batteries. The predicted characteristic peaks of infrared and Raman spectra provide useful information for in situ experimental investigation. Our work represents a significant step towards understanding (MgS)n clusters and improving the performance of Mg-S batteries.

Quantitative biochemical phenotypic heterogeneity of macrophages after myelin debris phagocytosis at a single cell level by synchrotron radiation fourier transform infrared microspectroscopy.

During the immuno-inflammatory pathophysiological process of spinal cord injury, traumatic brain injury, and ischemic stroke, macrophages play an important role in phagocytizing and clearing degenerated myelin debris. After phagocytizing myelin debris, the biochemical phenotypes related to the biological function of macrophages show vast heterogeneity; however, it is not fully understood. Detecting biochemical changes after myelin debris phagocytosis by macrophages at a single-cell level is helpful to characterize phenotypic and functional heterogeneity. In this study, based on the cell model of myelin debris phagocytosis by macrophages in vitro, the biochemical changes in macrophages were investigated using Synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy. Infrared spectrum fluctuations, principal component analysis, and cell-to-cell Euclidean distance statistical analysis of specific spectrum regions revealed dynamic and significant changes in proteins and lipids within macrophages after myelin debris phagocytosis. Thus, SR-FTIR microspectroscopy is a powerful identification toolkit for exploring biochemical phenotype heterogeneity transformation that may be of great importance to providing an evaluation strategy for studying cell functions related to cellular substance distribution and metabolism.

Identification of Cathepsin B as a Therapeutic Target for Ferroptosis of Macrophage after Spinal Cord Injury.

Hemorrhage and immune cell infiltration are the main pathological features of spinal cord injury (SCI). Excessive iron deposition is caused by leaking hemosiderin which may over-activate ferroptosis pathways, resulting in lipid peroxidation and mitochondrial dysfunction in cells. Inhibiting ferroptosis after SCI has been shown to aid functional recovery. However, the essential genes involved in cellular ferroptosis following SCI are still unknown. Here we show that Ctsb is a statistical significance gene by collecting multiple transcriptomic profiles and identifying differentially expressed ferroptosis-related genes, which are abundantly expressed in myeloid cells after SCI and widely distributed at the epicenter of the injury. The expression score of ferroptosis, calculated by ferroptosis driver/suppressor genes, was high in macrophages. Furthermore, we discovered that inhibiting cathepsin B (CTSB), specifically with a small-molecule drug, CA-074-methyl ester (CA-074-me), reduced lipid peroxidation and mitochondrial dysfunction in macrophages. We also found that alternatively activated M2-polarized macrophages are more susceptible to hemin-induced ferroptosis. Consequently, CA-074-me could reduce ferroptosis, induce M2 macrophage polarization, and promote the neurological function recovery of mice after SCI. Our study comprehensively analyzed the ferroptosis after SCI from the perspective of multiple transcriptomes and provided a novel molecular target for SCI treatment.

Microcarriers promote the through interface movement of mouse trophoblast stem cells by regulating stiffness.

Mechanical force is crucial in the whole process of embryonic development. However, the role of trophoblast mechanics during embryo implantation has rarely been studied. In this study, we constructed a model to explore the effect of stiffness changes in mouse trophoblast stem cells (mTSCs) on implantation: microcarrier was prepared by sodium alginate using a droplet microfluidics system, and mTSCs were attached to the microcarrier surface with laminin modifications, called T(micro). Compared with the spheroid, formed by the self-assembly of mTSCs (T(sph)), we could regulate the stiffness of the microcarrier, making the Young's modulus of mTSCs (367.70 ± 79.81 Pa) similar to that of the blastocyst trophoblast ectoderm (432.49 ± 151.90 Pa). Moreover, T(micro) contributes to improve the adhesion rate, expansion area and invasion depth of mTSCs. Further, T(micro) was highly expressed in tissue migration-related genes due to the activation of the Rho-associated coiled-coil containing protein kinase (ROCK) pathway at relatively similar modulus of trophoblast. Overall, our study explores the embryo implantation process with a new perspective, and provides theoretical support for understanding the effect of mechanics on embryo implantation.

Advanced Platelet-Rich Fibrin Extract Treatment Promotes the Proliferation and Differentiation of Human Adipose-Derived Mesenchymal Stem Cells through Activation of Tryptophan Metabolism.

BACKGROUND: Advanced platelet-rich fibrin extract (APRFE) contains a high concentration of various cytokines that are helpful for improving stem cells repair function. OBJECTIVE: However, the underlying mechanism of APRFE improving stem cell repairing is not clear. METHODS: We produced APRFE by centrifuging fresh peripheral blood samples and isolated and identified human adipose-derived mesenchymal stem cells (ADMSCs). The abundance of cytokines contained in APRFE was detected by the Enzyme-linked immunosorbent assay (ELISA). The ADMSCs treated with or without APRFE were collected for transcriptome sequencing. RESULTS: Based on the sequencing data, the expression profiles were contracted. The differentially expressed genes and lncRNA (DEGs and DElncRNAs) were obtained using for the differential expression analysis. The lncRNA-miRNA-mRNA network was constructed based on the miRNet database. The further enrichment analysis results showed that the biological functions were mainly related to proliferation, differentiation, and cell-cell function. To explore the role of APRFE, the protein-protein interaction network was constructed among the cytokines included in APRFE and DEGs. Furthermore, we constructed the global regulatory network based on the RNAInter and TRRUST database. The pathways in the global regulatory network were considered as the core pathways. We found that the DEGs in the core pathways were associated with stemness scores. CONCLUSION: In summary, we predicted that APRFE activated three pathways (tryptophan metabolism, mTOR signaling pathway, and adipocytokine signaling) to promote the proliferation and differentiation of ADMSCs. The finding may be helpful for guiding the application of ADMSCs in the clinic.

Pestalotiopols E-J, Six New Polyketide Derivatives from a Marine Derived Fungus Pestalotiopsis sp. SWMU-WZ04-1.

Chemical epigenetic cultivation of the sponge-derived fungus Pestalotiopsis sp. SWMU-WZ04-1 contributed to the identification of twelve polyketide derivatives, including six new pestalotiopols E-J (1-6) and six known analogues (7-12). Their gross structures were deduced from 1D/2D NMR and HRESIMS spectroscopic data, and their absolute configurations were further established by circular dichroism (CD) Cotton effects and the modified Mosher's method. In the bioassay, the cytotoxic and antibacterial activities of all compounds were evaluated. Chlorinated benzophenone derivatives 7 and 8 exhibited inhibitory effects on Staphylococcus aureus and Bacillus subtilis, with MIC values varying from 3.0 to 50 µg/mL. In addition, these two compounds were cytotoxic to four types of human cancer cells, with IC50 values of 16.2~83.6 µM. The result showed that compound 7 had the probability of being developed into a lead drug with antibacterial ability.

Efficacy of electro-acupuncture in postpartum with diastasis recti abdominis: A randomized controlled clinical trial.

Background: Electro-acupuncture (EA) has promising effects on diastasis rectus abdominis (DRA), defined as a separation of the two muscle bellies of rectus abdominis. To study, there is scant knowledge or scarce high-quality evidence. Objective: We aimed to evaluate the long-term efficacy and safety of EA in treating DRA during postpartum. It was assumed that the improvement of DRA was more obvious in the EA group than in the control group. Design: Randomized, controlled, blinded trial (Clinical Trial Registration: ChiCTR2100041891). Setting: Hangzhou Hospital of Traditional Chinese Medicine in China. Participants: Females aged 20-45 years without a past medical history of pathological rectus abdominal dissection were recruited from DRA inclusion criteria from 42 days to 1 year postpartum. Intervention: 110 participants were randomly assigned in a 1:1 ratio to a control group with no EA intervention (n = 55), and EA group (n = 55). The EA group received ten sessions of EA combined with physical exercise or only physical exercise for 2 weeks with a 26-week follow-up. Measurements: Outcomes were assessed at baseline, week 2, and week 26. The primary outcome was the change of the inter recti distance (IRD) and electromyographic evaluation of the pelvic floor. Secondary outcomes included elasticity of linea alba (LA), paraumbilical subcutaneous adipose tissue (SAT) measurement, body mass index (BMI), percentage body fat (F%), dyspepsia symptoms, menstrual symptoms, quality of life (QoL), pain performance of patients with lower back pain, postnatal depression symptoms (PDS), postpartum self-image, and DRA-related symptom assessment including urine leakage, frequency, and urgency, constipation, sexual dysfunction, and chronic pelvic pain. Results: A total of 110 maternal (55 in each group) were recruited. The mean difference in IRD from baseline to week 2 and week 26 in all states of the two groups were reduced compared with those before treatment, with statistical significance (P < 0.05). The mean of IRD at the horizontal line of the umbilicus in the end-expiratory state was smaller in the EA group than in the control group, but the difference was not statistically significant (P > 0.05) at week 2. The mean of IRD at the horizontal line of the umbilicus in head-up and flexed knee state was smaller in the EA group than in the control group, and the difference was statistically significant (P < 0.05) at week 26. Five (9.1%) and thirteen (23.64%) adverse events were reported in EA and control groups, respectively. No serious adverse events were reported. Limitation: The frequency intensity of EA parameters was selected between 4 and 6 because of individual tolerance differences. Conclusion: EA is an effective approach to improve IRD, electromyographic evaluation of the pelvic floor, BMI, the elasticity of LA, paraumbilical SAT, and symptoms of DRA, with durable effects at 26 weeks. Primary funding source: The Construction Fund of Medical Key Disciplines of Hangzhou (Project Number: OO20200097), Hangzhou Medical and Health Science and Technology Project No. A20200483, and Zhejiang Traditional Chinese Medicine Science and Technology Plan Project (Project Number: 2021ZQ065). Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR2100041891.