Biomaterials-Based Technologies in Skeletal Muscle Tissue Engineering.

For many clinically prevalent severe injuries, the inherent regenerative capacity of skeletal muscle remains inadequate. Skeletal muscle tissue engineering (SMTE) seeks to meet this clinical demand. With continuous progress in biomedicine and related technologies including micro/nanotechnology and 3D printing, numerous studies have uncovered various intrinsic mechanisms regulating skeletal muscle regeneration and developed tailored biomaterial systems based on these understandings. Here, the skeletal muscle structure and regeneration process are discussed and the diverse biomaterial systems derived from various technologies are explored in detail. Biomaterials serve not merely as local niches for cell growth, but also as scaffolds endowed with structural or physicochemical properties that provide tissue regenerative cues such as topographical, electrical, and mechanical signals. They can also act as delivery systems for stem cells and bioactive molecules that have been shown as key participants in endogenous repair cascades. To achieve bench-to-bedside translation, the typical effect enabled by biomaterial systems and the potential underlying molecular mechanisms are also summarized. Insights into the roles of biomaterials in SMTE from cellular and molecular perspectives are provided. Finally, perspectives on the advancement of SMTE are provided, for which gene therapy, exosomes, and hybrid biomaterials may hold promise to make important contributions.

Effect and pharmacological mechanism of Salvia miltiorrhiza and its characteristic extracts on diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is a severe diabetic microvascular complication with an increasing prevalence rate and lack of effective treatment. Traditional Chinese medicine has been proven to have favorable efficacy on DN, especially Salvia miltiorrhiza Bunge (SM), one of the most critical and conventional herbs in the treatment. Over the past decades, studies have demonstrated that SM is a potential treatment for DN, and the exploration of the underlying mechanism has also received much attention. AIM OF THIS REVIEW: This review aims to systematically study the efficacy and pharmacological mechanism of SM in the treatment of DN to understand its therapeutic potential more comprehensively. MATERIALS AND METHODS: Relevant information was sourced from Google Scholar, PubMed, Web of Science, and CNKI databases. RESULTS: Several clinical trials and systematic reviews have indicated that SM has definite benefits on the kidneys of diabetic patients. And many laboratory studies have further revealed that SM and its characteristic extracts, mainly including salvianolic acids and tanshinones, can exhibit pharmacological activity against DN by the regulation of metabolism, renal hemodynamic, oxidative stress, inflammation, fibrosis, autophagy, et cetera, and several involved signaling pathways, thereby preventing various renal cells from abnormal changes in DN, including endothelial cells, podocytes, epithelial cells, and mesangial cells. CONCLUSION: As a potential drug for the treatment of DN, SM has multi-component, multi-target, and multi-pathway pharmacological effects. This work will not only verify the satisfactory curative effect of SM in the treatment of DN but also provide helpful insights for the development of new anti-DN drugs and the application of traditional Chinese medicine.

Preliminary study of finger temperature recovery in patients with diabetes mellitus following cold stimulation.

OBJECTIVE: To explore the difference in temperature recovery following cold stimulation between participants with and without diabetes mellitus (DM). MATERIALS AND METHODS: The participants without (control group; n = 25) and with (DM group; n = 26) DM were subjected to local cold stimulation (10º C for 90 s). The thermal images of their hands were continuously captured using a thermal camera within 7 min following cold stimulation, and the highest temperature of each fingertip was calculated. According to the temperature values at different timepoints, the temperature recovery curves were drawn, and the baseline temperature (T-base), initial temperature after cooling (T0), temperature decline amplitude (T-range), and area under the temperature recovery curve > T0 (S) were calculated. Finally, symmetry differences between the two groups were analysed. RESULTS: No statistical differences in the T-base, T0, and T-range were observed between the DM and control groups. After drawing the rewarming curve according to the temperature of the fingertips of the patients following cold stimulation, the S in the DM group was significantly lower than that in the control group (p < 0.05). Furthermore, the asymmetry of the base temperature of the hand was observed in the DM group. CONCLUSIONS: Following cold stimulation, the patients with DM exhibited a different rewarming pattern than those without DM. Thus, cold stimulation tests under infrared thermography may contribute to the early screening of diabetic peripheral neuropathy in future.

Long head of biceps tendon transposition for massive and irreparable rotator cuff tears: A systematic review and meta-analysis.

BACKGROUND: Superior capsular reconstruction (SCR) with long head of biceps tendon (LHBT) transposition was developed to massive and irreparable rotator cuff tears (MIRCTs); however, the outcomes of this technique remain unclear. AIM: To perform a systematic review of biomechanical outcomes and a meta-analysis of clinical outcomes after LHBT transposition for MIRCTs. METHODS: We performed a systematic electronic database search on PubMed, EMBASE, and Cochrane Library. Studies of SCR with LHBT transposition were included according to the inclusion and exclusion criteria. Biomechanical studies were assessed for main results and conclusions. Included clinical studies were evaluated for quality of methodology. Data including study characteristics, cohort demographics, and outcomes were extracted. A meta-analysis was conducted of the clinical outcomes. RESULTS: According to our inclusion and exclusion criteria, a total of six biomechanical studies were identified and reported an overall improvement in subacromial contact pressures and prevention of superior humeral migration without limiting range of motion (ROM) after LHBT transposition for MIRCTs. A total of five clinical studies were included in the meta-analysis of LHBT transposition outcomes, consisting of 253 patients. The results indicated that compared to other surgical methods for MIRCTs, LHBT transposition had advantages of more significant improvement in ROM (forward flexion mean difference [MD] = 6.54, 95% confidence interval [CI]: 3.07-10.01; external rotation [MD = 5.15, 95%CI: 1.59-8.17]; the acromiohumeral distance [AHD] [MD = 0.90, 95%CI: 0.21-1.59]) and reducing retear rate (odds ratio = 0.27, 95%CI: 0.15-0.48). No significant difference in American Shoulder and Elbow Surgeons score, visual analogue scale score, and University of California at Los Angles score was demonstrated between these two groups for MIRCTs. CONCLUSION: In general, SCR with LHBT transposition was a reliable and economical technique for treating MIRCTs, both in terms of biomechanical and clinical outcomes, with comparable clinical outcomes, improved ROM, AHD, and reduced the retear rates compared to conventional SCR and other established techniques. More high-quality randomized controlled studies on the long-term outcomes of SCR with LHBT transposition are required to further assess.

Transtendon technique versus repair after completion of the tear for articular-sided partial rotator cuff tear: a meta-analysis of comparative studies.

BACKGROUND: Transtendon repair and repair after completion of the tear have been widely used to treat partial-thickness rotator cuff tears (PT-RCTs). The present study was aimed to compare the clinical outcomes and tendon integrity following arthroscopic repair of articular PT-RCTs using transtendon repair or repair after completion of the tear. METHODS: We performed a systematic electronic database search on Cochrane Central Register of Controlled Trials, PubMed and Embase to identify articles equating articular-sided PT-RCTs repair. The randomized controlled clinical trials that met our criteria were evaluated for quality of methodology. The results obtained were further analyzed and correlated to present the benefits and drawbacks comparing the two surgical procedures. RESULT: According to our inclusion and exclusion criteria, six articles were included in the present study. A total of 501 patients were analyzed as part of this study. The results indicated that both the surgical treatments provided excellent functional improvements and tendon integrity. However, no significant differences for the visual analogue scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, constant score, range of motion, postoperative adhesive capsulitis, tendon integrity and patient satisfaction were found between the two cohorts (p > 0.05). CONCLUSIONS: Both transtendon technique and repair after completion of the tear for articular-sided partial rotator cuff tear provide improvements in clinical outcome with a low complication rate and a high rate of healing.

Anti-Aging Effects of Anthocyanin Extracts of Sambucus canadensis Caused by Targeting Mitochondrial-Induced Oxidative Stress.

Anthocyanin is a natural antioxidant agent extracted from the fruits of Sambucus canadensis, which has been considered to have potential anti-aging effects. Cell senescence is the primary cause of aging and related diseases. Recently, research on the development of compounds for eliminating senescent cells or damaged organs have shown prospects. The compounds which promote the clearing of senescent cells are called "senolytics". Though anthocyanin is considered to have potential anti-aging effects owing to its anti-inflammatory and antioxidant activities, the mechanism of the elimination of senescent cells remains unclear. In this study, we prepared anthocyanins extracted from the fruits of Sambucus canadensis and evaluated their anti-aging effects in vivo and in vitro. We found that anthocyanin could significantly reduce cell senescence and aging of the lens by inhibiting the activity of the PI3K/AKT/mTOR signaling pathway, consequently promoting the apoptosis of senescent cells, increasing the autophagic and mitophagic flux, and enhancing the renewal of mitochondria and the cell to maintain cellular homeostasis, leading to attenuating aging. Therefore, our study provided a basis for anthocyanin to be used as new "senolytics" in anti-aging.

Deuterohemin-Ala-His-Thr-Val-Glu-Lys (DhHP-6) Mimicking Enzyme as Synergistic Antioxidant and Anti-Inflammatory Material for Periodontitis Therapy.

Periodontitis is an inflammatory disease induced by plaque microorganisms. In the clinic, antibiotic assistant periodontal mechanical therapy is the most effective therapy for the treatment of periodontitis. However, the drug resistance of the antibiotics and the repeated coming and diminishing of the disorder of oxidation-reduction balance in the inflammatory tissue could not meet the high requirements for periodontic health control in long periods. Deuterohemin-ala-his-thr-val-glu-lys (DhHP-6) is a biomimetic oxidase-mimicking enzyme that simulates the reactive oxygen radical scavenger function of heme by synthesizing the new molecular material following the key structure and amino acid sequence of heme. In this article, we report the antioxidant and anti-inflammatory properties of DhHP-6 by building a inflammatory model for human gingival fibroblasts (HGFs) stimulated by lipolysaccharide (LPS) and its effects on periodontitis in Wistar rats. DhHP-6 reduced the oxidative stress of HGFs by increasing the amount of the reductase species of glutathione (GSH) and catalase (CAT) while decreasing the amount of oxidase species of malonaldehyde (MDA) and reactive oxygen species (ROS). DhHP-6 had a dose-dependent protective effect on alveolar bone absorption in rats with periodontitis, enhanced antioxidant capacity, and reduced inflammation. As determined by Micro-CT scanning, DhHP-6 reduced alveolar bone loss and improved the bone structure of the left maxillary first molar of rats. There were no obvious morphological and histological differences in the rat organs with or without DhHP-6 treatment. These results suggest that DhHP-6 can be used to treat periodontitis by increasing the expression levels of antioxidant enzymes and antioxidants in systemic and local tissues, thereby reducing levels of oxidation products and cyto-inflammatory factors. The synergistic antioxidant and anti-inflammatory effects of DhHP-6 suggest that there are promising applications of this biomimetic enzyme molecular material for the next generation of agents for periodontitis therapy.

Hyaluronic Acid-Enwrapped Polyoxometalate Complex for Synergistic Near Infrared-II Photothermal/Chemo-Therapy and Chemodynamic Therapy.

To enhance the efficacy of tumor therapy, the collection of functional components into a targeting system shows advantages over most homogeneous materials in inducing apoptosis of cancer cells. The security and targeting of therapeutic agents also require the effect combination of additional components. However, the construction of multifunctional composites in a simple system with intelligent cooperative responsiveness remains a challenge. Herein, a reduced polyanionic cluster (rP2W18) bearing the absorption at the near infrared (NIR) II region is used as a core carrier to bind the positively charged doxorubicin hydrochloride (DOX) through ionic interaction. To reduce the physiological toxicity, hyaluronic acid grafting ß-cyclodextrin side chains is used to cover the ionic complex through host-guest inclusion to DOX. When the nanocomposite is activated by local laser exposure, the final three-component therapeutic agent is demonstrated to present targeted photothermal conversion capability and chemodynamic activity together with chemotherapy. With the controlled release of DOX under the stimulation of mild acidity in the tumor region and photothermal effect, the exposed rP2W18 is aroused by hydrogen peroxide overexpressed in a tumor microenvironment to produce toxic reactive oxygen species, 1O2. This work presents an opportunity for the development of a nanocomposite in NIR-II photothermal/chemo-therapy and chemodynamic synergistic therapy.

Metformin Attenuates UVA-Induced Skin Photoaging by Suppressing Mitophagy and the PI3K/AKT/mTOR Pathway.

Ultraviolet (UV) radiation is a major cause of photoaging that can induce DNA damage, oxidative stress, and cellular aging. Metformin (MF) can repair DNA damage, scavenge reactive oxygen species (ROS), and protect cells. However, the mechanism by which MF inhibits cell senescence in chronic skin damage induced by UVA is unclear. In this study, human foreskin fibroblasts (HFFs) treated with UVA were used as an in vitro model and UVA-induced skin photoaging in Kunming mice was used as an in vivo model to investigate the potential skin protective mechanism of MF. The results revealed that MF treatment attenuated UVA-induced cell viability, skin aging, and activation of the PI3K/AKT/mTOR signaling pathway. Furthermore, MF treatment alleviated the mitochondrial oxidative stress and decreased mitophagy. Knockdown of Parkin by siRNA increased the clearance of MF in senescent cells. The treatment of Kunming mice with MF at a dose of 10 mg/kg/day significantly reduced UVA-induced skin roughness, epidermal thinning, collagen degradation, and skin aging. In conclusion, our experimental results suggest that MF exerts anti-photoaging effects by inhibiting mitophagy and the PI3K/AKT/mTOR signaling pathway. Therefore, our study improves the current understanding of the protective mechanism of MF against photoaging.

Charge-Transfer Complex Combining Reduced Cluster with Enhanced Stability for Combined Near-Infrared II Photothermal Therapy.

In the search for materials with enhanced near-infrared (NIR) photothermal properties and capability of providing environment-sensitive therapy, a method that combines isolated components into one nanocomposite is developed. The technique simultaneously involves redox, charge-transfer formation, and ionic complexation. During the polyoxophosphomolybdate (PMo) cluster mixing with biosafe chromogen 3,3',5,5'-tetramethylbenzidine (TMB), the reduced state (rPMo) and the oxidized TMB in the state of charge-transfer complex (cTMB) emerge spontaneously. The two reduced and oxidized components with charges form a stable ionic complex that resists physiology, saline, broad pH, and elevated temperature. Both the rPMo and cTMB contribute to the total sustainable photothermal conversion efficiency of 48.4% in the NIR-II region. The ionic complex exhibits biocompatibility in in vitro cell viability evaluation and is demonstrated to enter tumor cells with sustained photothermal property and complexation stability. Due to the local acidity that triggers further interaction among rPMo clusters, a distinct accumulation of the ionic complex at the tumor position is observed after caudal vein injection. Moreover, a remarkable local NIR-II photothermal image appears. The diminishment of tumor in mice with maintained body weight demonstrates the comprehensive effect of this NIR-II photothermal therapeutic material.

First Indirect Drive Experiment Using a Six-Cylinder-Port Hohlraum.

The new hohlraum experimental platform and the quasi-3D simulation model are developed to enable the study of the indirect drive experiment using the six-cylinder-port hohlraum for the first time. It is also the first implosion experiment for the six laser-entrance-hole hohlraum to effectively use all the laser beams of the laser facility that is primarily designed for the cylindrical hohlraum. The experiments performed at the 100 kJ Laser Facility produce a peak hohlraum radiation temperature of ∼222 eV for ∼80 kJ and 2 ns square laser pulse. The inferred x-ray conversion efficiency η∼87% is similar to the cylindrical hohlraum and higher than the octahedral spherical hohlraum at the same laser facility, while the low laser backscatter is similar to the outer cone of the cylindrical hohlraum. The hohlraum radiation temperature and M-band (>1.6 keV) flux can be well reproduced by the quasi-3D simulation. The variations of the yield-over-clean and the hot spot shape can also be semiquantitatively explained by the calculated major radiation asymmetry of the quasi-3D simulation. Our work demonstrates the capability for the study of the indirect drive with the six-cylinder-port hohlraum at the cylindrically configured laser facility, which is essential for numerically assessing the laser energy required by the ignition-scale six-cylinder-port hohlraum.

Measurement of Time-Dependent Drive Flux on the Capsule for Indirectly Driven Inertial Confinement Fusion Experiments.

A new method for measuring the time-dependent drive flux at the hohlraum center is proposed as a better alternative to conventional wall-based techniques. The drive flux here is obtained by simultaneous measurement of the reemitted flux and shock velocity from a three-layered "cakelike" sample. With these two independent observables, the influence induced by the uncertainty of the material parameters of the sample can be effectively decreased. The influence from the closure of the laser entrance hole, which was the main challenge in conventional wall-based techniques, was avoided through localized reemitted flux measurement, facilitating drive flux measurement throughout the entire time history. These studies pave a new way for probing the time-dependent drive flux, for both cylindrical hohlraums and novel hohlraums with six laser entrance holes.

Highly thermal stable RNase A@PbS/ZnS quantum dots as NIR-IIb image contrast for visualizing temporal changes of microvasculature remodeling in flap.

Surgeons face great challenges in acquiring high-performance imaging because fluorescence probes with desired thermal stability remains rare. Here, hybrid lead sulfide/zinc sulfide quantum dots (PbS/ZnS QDs) nanostructures emitting in the long-wavelength end of the second near-infrared (NIR-IIb) window were synthesized and conjugated with Ribonuclease-A (RNase A). Such formed RNase A@PbS/ZnS QDs exhibited strong NIR IIb fluorescence and thermal stability, as supported by the photoluminescent emission assessment at different temperatures. This will allow the RNase A@PbS/ZnS QDs to provide stable fluorescence signals for long-time intraoperative imaging navigation, despite often happened, undesirable thermal accumulation in vivo. Compared to NIR-IIa fluorescence imaging, NIR-IIb vascular fluorescence imaging achieved larger penetration depth, higher signal/background ratios and nearly zero endogenous tissue autofluorescence. Moreover, these QDs illustrate the reliability during the real-time and long-time precise assessment of flap perfusion by clearly visualizing microvasculature map. These findings contribute to intraoperative imaging navigation with higher precision and lower risk.

Monitoring Rotator Cuff Muscle Fatty Infiltration Progression by Magnetic Resonance Imaging T1 Mapping: Correlation With Direct Evaluation Findings in Rats.

BACKGROUND: Monitoring the fatty infiltration (FI) process in rotator cuff muscles is of value in establishing a treatment plan and predicting the postoperative prognosis. Quantitative T1 mapping shows promise for evaluating muscle degeneration, while its validity in monitoring rotator cuff muscle FI progression needs further investigation. PURPOSE: To determine the validity of T1 mapping in monitoring FI progression of rotator cuff muscles. STUDY DESIGN: Controlled laboratory study. METHODS: Sprague-Dawley rats (N = 108) underwent left supraspinatus (SS) and infraspinatus (IS) tenotomy only (TT), suprascapular nerve transection only (NT), or SS and IS tenotomy plus suprascapular nerve transection (TT+NT). Sham surgery on the right shoulder served as the control. The magnetic resonance imaging examination included T1 mapping performed at 12, 16, and 20 weeks postoperation. SS and IS muscles were harvested to quantitatively evaluate FI via direct evaluation (triglyceride quantification assay and histological analysis) at the same predetermined intervals. The correlation of the imaging data with direct evaluation of rotator cuff muscles was analyzed. RESULTS: T1 values were significantly lower in left SS and IS muscles at 12, 16, and 20 weeks postoperation as compared with those on the right side. T1 values of the left SS and IS muscles were continuously decreased in all groups. The TT+NT group had a greater decrease in T1 value than did the TT and NT groups. Triglyceride quantification assay and histological analysis demonstrated significant and progressive FI of the left SS and IS muscles in the 3 groups. The most serious FI changes were observed in the TT+NT group. T1 values were also well correlated with triglyceride contents and area fractions of fat. CONCLUSION: T1 mapping can be an effective imaging modality for sensitive and quantitative monitoring of FI progression in rotator cuff muscles. CLINICAL RELEVANCE: The findings of this study provide a tool for researchers to noninvasively and quantitatively monitor the process of muscle degeneration, contributing to the evaluation of surgical indication and postoperative prognosis.

Nerve Suture Combined With ADSCs Injection Under Real-Time and Dynamic NIR-II Fluorescence Imaging in Peripheral Nerve Regeneration in vivo.

Peripheral nerve injury gives rise to devastating conditions including neural dysfunction, unbearable pain and even paralysis. The therapeutic effect of current treatment for peripheral nerve injury is unsatisfactory, resulting in slow nerve regeneration and incomplete recovery of neural function. In this study, nerve suture combined with ADSCs injection was adopted in rat model of sciatic nerve injury. Under real-time visualization of the injected cells with the guidance of NIR-II fluorescence imaging in vivo, a spatio-temporal map displaying cell migration from the proximal injection site (0 day post-injection) of the nerve to the sutured site (7 days post-injection), and then to the distal section (14 days post-injection) was demonstrated. Furthermore, the results of electromyography and mechanical pain threshold indicated nerve regeneration and functional recovery after the combined therapy. Therefore, in the current study, the observed ADSCs migration in vivo, electrophysiological examination results and pathological changes all provided robust evidence for the efficacy of the applied treatment. Our approach of nerve suture combined with ADSCs injection in treating peripheral nerve injury under real-time NIR-II imaging monitoring in vivo added novel insights into the treatment for peripheral nerve injury, thus further enhancing in-depth understanding of peripheral nerve regeneration and the mechanism behind.

EMPress Enables Tree-Guided, Interactive, and Exploratory Analyses of Multi-omic Data Sets.

Standard workflows for analyzing microbiomes often include the creation and curation of phylogenetic trees. Here we present EMPress, an interactive web tool for visualizing trees in the context of microbiome, metabolome, and other community data scalable to trees with well over 500,000 nodes. EMPress provides novel functionality-including ordination integration and animations-alongside many standard tree visualization features and thus simplifies exploratory analyses of many forms of 'omic data.IMPORTANCE Phylogenetic trees are integral data structures for the analysis of microbial communities. Recent work has also shown the utility of trees constructed from certain metabolomic data sets, further highlighting their importance in microbiome research. The ever-growing scale of modern microbiome surveys has led to numerous challenges in visualizing these data. In this paper we used five diverse data sets to showcase the versatility and scalability of EMPress, an interactive web visualization tool. EMPress addresses the growing need for exploratory analysis tools that can accommodate large, complex multi-omic data sets.

In Vivo Dynamic Monitoring of Bacterial Infection by NIR-II Fluorescence Imaging.

Time window of antibiotic administration is a critical but long-neglected point in the treatment of bacterial infection, as unnecessary prolonged antibiotics are increasingly causing catastrophic drug-resistance. Here, a second near-infrared (NIR-II) fluorescence imaging strategy based on lead sulfide quantum dots (PbS QDs) is presented to dynamically monitor bacterial infection in vivo in a real-time manner. The prepared PbS QDs not only provide a low detection limit (104 CFU mL-1 ) of four typical bacteria strains in vitro but also show a particularly high labeling efficiency with Escherichia coli (E. coli). The NIR-II in vivo imaging results reveal that the number of invading bacteria first decreases after post-injection, then increases from 1 d to 1 week and drop again over time in infected mouse models. Meanwhile, there is a simultaneous variation of dendritic cells, neutrophils, macrophages, and CD8+ T lymphocytes against bacterial infection at the same time points. Notably, the infected mouse self-heals eventually without antibiotic treatment, as a robust immune system can successfully prevent further health deterioration. The NIR-II imaging approach enables real-time monitoring of bacterial infection in vivo, thus facilitating spatiotemporal deciphering of time window for antibiotic treatment.

Epoxycytochalasin H: An Endophytic Phomopsis Compound Induces Apoptosis in A2780 Cells Through Mitochondrial Damage and Endoplasmic Reticulum Stress.

BACKGROUND: Natural compounds extracted from plants have been reported to have antitumor activity. A fungal metabolite from Phomopsis, identified as epoxycytochalasin H and isolated from the flowering plant Polygonatum sibiricum, was found to have significant antitumor activity. In this study, we report the antitumor effects and mechanism of action of epoxycytochalasin H in the ovarian cancer cell line A2780. Our data suggest that epoxycytochalasin H markedly reduces cell proliferation and induces apoptosis in ovarian cancer cells. MATERIALS AND METHODS: The viability, apoptosis and colony formation of A2780 cells, treated with epoxycytochalasin H, were detected by MTT assay, nuclear staining, flow cytometry, and clone formation assay. MitoROS and mitochondrial membrane potentials were detected by MitoSOX staining and flow cytometry. The expression of proteins associated with apoptosis, autophagy, and endoplasmic reticulum stress, in A2780 cells treated with epoxycytochalasin H, was detected by Western blot. Effects of mitophagy were detected in Parkin-overexpressing 293T cells. RESULTS: Our data suggested that epoxycytochalasin H could strongly reduce cell proliferation and induce apoptosis in ovarian cancer cell line A2780. Epoxycytochalasin H induced apoptosis through mitochondrial injury, mitophagy, and endoplasmic reticulum stress. Specifically, epoxycytochalasin H increased ROS level in cells, and in mitochondria, it decreased mitochondrial membrane potential, caused mitochondrial injury, activated macroautophagy and mitophagy, and subsequently induced apoptosis via the mitochondrial pathway. Additionally, it was discovered that epoxycytochalasin H could induce apoptosis more significantly in 293T cells overexpressing Parkin than in the parental cells. Thus, the mitophagy activated by epoxycytochalasin H could promote apoptosis. In addition, epoxycytochalasin H mediated endoplasmic reticulum stress-related apoptosis. CONCLUSION: Epoxycytochalasin H could promote apoptosis of human ovarian cancer A2780 cells by activating mitochondrial and endoplasmic reticulum stress-related apoptotic pathways.

Phylogenomics of 10,575 genomes reveals evolutionary proximity between domains Bacteria and Archaea.

Rapid growth of genome data provides opportunities for updating microbial evolutionary relationships, but this is challenged by the discordant evolution of individual genes. Here we build a reference phylogeny of 10,575 evenly-sampled bacterial and archaeal genomes, based on a comprehensive set of 381 markers, using multiple strategies. Our trees indicate remarkably closer evolutionary proximity between Archaea and Bacteria than previous estimates that were limited to fewer "core" genes, such as the ribosomal proteins. The robustness of the results was tested with respect to several variables, including taxon and site sampling, amino acid substitution heterogeneity and saturation, non-vertical evolution, and the impact of exclusion of candidate phyla radiation (CPR) taxa. Our results provide an updated view of domain-level relationships.

Visualizing the Fate of Intra-Articular Injected Mesenchymal Stem Cells In Vivo in the Second Near-Infrared Window for the Effective Treatment of Supraspinatus Tendon Tears.

Mesenchymal stem cells (MSCs) are capable of exerting strong therapeutic potential for the treatment of supraspinatus tendon tear. However, MSC therapy remains underutilized and perhaps underrated due to the limited evidence of dynamic visualization of cellular behavior in vivo. Here, second near-infrared fluorescence imaging with biocompatible PbS quantum dots (QDs) provides a cellular migration map and information on the biodistribution and clearance processes of three densities of intra-articularly injected, labeled MSCs to treat supraspinatus tendon tear in mice. Intra-articular injection avoids entrapment of MSCs by filter organs and reduces the QD-induced organ toxicity. Notably, the MSCs share a similar migration direction, but the moderate density group is somewhat more efficient, showing the longest residence time and highest cell retention rate around the footprint during the repair stage. Furthermore, quantitative kinetic investigation demonstrates that labeled MSCs are cleared by feces and urine. Histomorphometric analysis demonstrates that the moderate density group achieves maximum therapeutic effect and labeled MSCs do not induce any injury or inflammation to major organs, which suggests that administration of too many or few MSCs may decrease their effectiveness. Such an imaging approach provides spatiotemporal evidence for response to MSC therapy in vivo, facilitating the optimization of MSC therapy.