Post-exercise left atrial conduit strain predicted hemodynamic change in heart failure with preserved ejection fraction.

OBJECTIVES: Left ventricle function directly impacts left atrial (LA) conduit function, and LA conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Pulmonary capillary wedge pressure (PCWP) before and during exercise is the current gold standard for diagnosing HFpEF. Post-exercise ΔPCWP can lead to worse long-term outcomes. This study examined the correlation between LA strain and post-exercise ΔPCWP in patients with HFpEF. METHODS: We enrolled 100 subjects, including 74 with HFpEF and 26 with non-cardiac dyspnea, from November 2017 to December 2020. Subjects underwent echocardiography, invasive cardiac catheterization, and expired gas analysis at rest and during exercise. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and PCWP were recorded during cardiac catheterization. Cardiac output, stroke volume, pulmonary vascular resistance, pulmonary artery compliance, systemic vascular resistance, and LV stroke work were calculated using standard formulas. RESULTS: Exercise LA conduit strain significantly correlated with both post-exercise ΔPCWP (r = - 0.707, p < 0.001) and exercise PCWP (r = - 0.659; p < 0.001). Exercise LA conduit strain differentiated patients who did and did not meet the 2016 European Society of Cardiology HFpEF criteria with an area under the curve of 0.69 (95% confidence interval, 0.548-0.831) using a cutoff value of 14.25, with a sensitivity of 0.64 and a specificity of 0.68. CONCLUSIONS: Exercise LA conduit strain significantly correlates with post-exercise ΔPCWP and has a comparable power to identify patients with HFpEF. Additional studies are warranted to confirm the ability of LA conduit strain to predict long-term outcomes among patients with HFpEF. CLINICAL RELEVANCE STATEMENT: Exercise left atrial conduit strain was highly associated with the difference of post-exercise pulmonary capillary wedge pressure and may indicate increased mortality risk in patients with heart failure with preserved ejection fraction, and also has comparable diagnostic ability. KEY POINTS: • Left atrial conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction. • Left atrial conduit strain during exercise can identify patients with heart failure with preserved ejection fraction. • Exercise left atrial conduit strain significantly correlates with the difference of pulmonary capillary wedge pressure during and before exercise which might predict the long-term outcomes of heart failure with preserved ejection fraction patients.

Enhancing the adsorption-photocatalytic efficiency of BiOBr for Congo red degradation by tuning the surface charge and bandgap via an Y3+-I- co-doping strategy.

Metal-ion doping and halogen substitution have been largely applied to tune the bandgap of bismuth oxybromide (BiOBr) to upgrade its photodegradation capacity. In this work, the adsorption capacity and photocatalytic behavior of solvothermally synthesized BiOBr photocatalysts can be optimized via the synergistic effect of Y3+- and I--doping. After an adsorption reaction in the dark and exposure for another 80 min to visible light, pure BiOBr can remove 46.5% of Congo red (CR) from water with an initial CR concentration of 50 mg L-1. Meanwhile, Bi0.8Y0.20OBr0.97I0.03, the co-doped catalyst, displays total degradation rates exceeding 98% and 92% with CR dosages of 50 and 100 mg L-1, respectively, demonstrating a doubled degradation capacity. With the co-doping solution, the negative charges on the catalysts reduce, more oxygen vacancies are generated, the bandgap remarkably narrows, and the photoabsorption range broadens for derivation of photoinduced electron-hole pairs. The mechanism for optimized photodegradation behavior and dramatically increased adsorption capacity are discussed based on analyses of the structural evolution, surface properties including the chemical state and surface charge, electrochemical performance and the yield/type of photogenerated species. Density functional theory (DFT) simulations were conducted to investigate the structural state, density of states (DOS) and electrostatic potential.

Insights into tolerance mechanisms of earthworms (Eisenia fetida) in copper-contaminated soils by integrating multi-omics analyses.

Earthworms can resist high levels of soil copper (Cu) contamination and play an essential role in absorbing them effectively. However, the molecular mechanisms underlying Cu tolerance in earthworms are poorly understood. To address this research gap, we studied alterations of Eisenia fetida in antioxidant enzymes, gut microbiota, metabolites, and genes under varying levels of Cu exposure soils (0, 67.58, 168.96, 337.92 mg/kg). Our results revealed a reduction in antioxidant enzyme activities across all treatment groups, indicating an adaptive response to alleviate Cu-induced oxidative stress. Analysis of gut microbiota revealed a significant increase in the abundance of bacteria associated with nutrient uptake and Cu2+ excretion under Cu stress. Furthermore, metabolomic analysis discovered an increase in certain metabolites associated with energy metabolism, such as pyruvic acid, L-malic acid, and fumaric acid, as Cu concentration escalated. These results suggested that enhanced energy supply contributes to the elevated tolerance of E. fetida towards Cu. Additionally, transcriptome analysis not only identified crucial detoxification genes (Hsp70, CTSL, GST, CHAC, and GCLC), but also confirmed the critical role of glutathione metabolism as a key pathway in E. fetida Cu detoxification processes. These findings provide a new perspective on the molecular mechanisms of Cu tolerance in earthworms.

Progesterone in Pregnancy: Evidence-Based Strategies to Reduce Miscarriage and Enhance Assisted Reproductive Technology.

The incidence of miscarriage in early pregnancy, between 5-20 weeks, is common, with a prevalence of between 5-22% of all pregnancies. Miscarriage can have physical, social, and mental health impacts on women and their families. In societies such as Taiwan, where the birth rate is falling and life expectancy is increasing, there is concern that factors that reduce birth rates will have detrimental economic and societal effects. Progesterone has a significant role in maintaining early and successful pregnancy to term. Evidence from preclinical and clinical research on the roles of progesterone has supported recent clinical guidelines in obstetrics and gynecology to reduce rates of early miscarriage and improve methods of assisted reproductive technology (ART). This article aims to present an evidence-based review of current recommendations for the use of progesterone in early pregnancy to reduce miscarriage rates and in luteal phase support for ART, including embryo transfer.

BNM-CDGNN: Batch Normalization Multilayer Perceptron Crystal Distance Graph Neural Network for Excellent-Performance Crystal Property Prediction.

Recently, in the field of crystal property prediction, the graph neural network (GNN) model has made rapid progress. The GNN model can effectively capture high-dimensional crystal features from the crystal structure, thereby achieving optimal performance in property prediction. However, the existing GNN model faces limitations in handling the hidden layer after the pooling layer, which restricts the training performance of the model. In the present research, we propose a novel GNN model called the batch normalization multilayer perceptron crystal distance graph neural network (BNM-CDGNN). BNM-CDGNN encodes the crystal's geometry structure only based on the distance vector between atoms. The graph convolutional layer utilizes the radial basis function as the attention mask, ensuring the crystal's rotation invariance and adding the geometric information on the crystal. Subsequently, the average pooling layer is connected after the convolutional layer to enhance the model's ability to learn precise information. BNM-CDGNN connects multiple hidden layers after the average pooling layers, and these layers are processed by the batch normalization layer. Finally, the fully connected layer maps the results to the target property. BNM-CDGNN significantly enhances the accuracy of crystal property prediction compared with previous baseline models such as SchNet, MPNN, CGCNN, MEGNet, and GATGNN.

Matrix-transmitted paratensile signaling enables myofibroblast-fibroblast cross talk in fibrosis expansion.

While the concept of intercellular mechanical communication has been revealed, the mechanistic insights have been poorly evidenced in the context of myofibroblast-fibroblast interaction during fibrosis expansion. Here we report and systematically investigate the mechanical force-mediated myofibroblast-fibroblast cross talk via the fibrous matrix, which we termed paratensile signaling. Paratensile signaling enables instantaneous and long-range mechanotransduction via collagen fibers (less than 1 s over 70 µm) to activate a single fibroblast, which is intracellularly mediated by DDR2 and integrin signaling pathways in a calcium-dependent manner through the mechanosensitive Piezo1 ion channel. By correlating in vitro fibroblast foci growth models with mathematical modeling, we demonstrate that the single-cell-level spatiotemporal feature of paratensile signaling can be applied to elucidate the tissue-level fibrosis expansion and that blocking paratensile signaling can effectively attenuate the fibroblast to myofibroblast transition at the border of fibrotic and normal tissue. Our comprehensive investigation of paratensile signaling in fibrosis expansion broadens the understanding of cellular dynamics during fibrogenesis and inspires antifibrotic intervention strategies targeting paratensile signaling.

Prediction of microdissection testicular sperm extraction outcomes of azoospermic patients post-chemotherapy using cyclophosphamide equivalent dose.

PURPOSE: We determined the sperm retrieval rate in men with persistent azoospermia post-chemotherapy in relation to cyclophosphamide equivalent dose (CED), a unit for quantifying alkylating agent exposure. METHODS: Medical records were retrospectively reviewed of 1098 patients diagnosed with non-obstructive azoospermia who had undergone microdissection testicular sperm extraction (mTESE) between January 2010 and 2021 at our institution. Twenty-three patients with a prior history of chemotherapy were included in the study. Oncological data, chemotherapy regime, and dosage were reviewed. The pretreatment hormone profile, CED, and mTESE outcomes were analyzed. RESULTS: Testicular spermatozoa were successfully retrieved from 11 patients (47%). The mean patient age was 37.3 years (range, 27-41 years), and mean time interval from chemotherapy to mTESE, 11.8 years (range, 1-45 years). Patients exposed to alkylating agents had significantly lower sperm retrieval rates than those not exposed to alkylating agents (1/9, 11% vs. 10/14, 71%, p = 0.009). No men with CED > 4000 mg/m2 (n = 6) had viable sperm in the testes during mTESE. Moreover, patients diagnosed with testicular non-seminomatous germ cell tumors had a favorable sperm retrieval rate (67%) compared to patients with lymphoma (20%) or leukemia (33%). CONCLUSION: Patients with permanent azoospermia post-chemotherapy have a lower testicular sperm retrieval rate when the chemotherapy regimen included alkylating agents. In cases where patients have undergone more intensive gonadotoxic treatments, such as higher CED, the likelihood of successful sperm retrieval is low. It is advisable to counsel such patients using the CED model prior to considering surgical sperm retrieval.

Effects of different colors of film mulch on soil temperature and rice growth in a non-flooded condition.

BACKGROUND: Rice cultivation under film mulching with no flooding is widely used as an effective water-saving technology. Different colors of film mulch have different effects on the soil hydrothermal environment and crop growth because of their different optical properties. However, the effects of different colors of film mulch on soil temperature and rice physiological growth are not clearly understood. RESULTS: Field experiments were conducted in 2019 and 2020 to investigate the effects of different color mulches on soil temperature and rice growth in a non-flooded condition. Transparent film (TM), black film (BM), two-color film (BWM, silver on the front and black on the back), and no film (NM) in a non-flooded condition were designed. Soil temperature variation at different soil depths of 0-0.25 m and rice plant height, stem thickness, dry matter, yield and quality were monitored. The results showed that compared to no mulching, the mulching treatment effectively increased the average soil temperature during the whole rice growth stage with the soil temperature ranked TM > BM > BWM. Compared with NM, the BM and BWM treatments increased rice yield by 12.1-17.7% and 6.4-14.4% in 2019 and 2020, respectively. The BWM had 18.2% and 6.8% greater gel consistency than NM in 2019 and 2020, respectively. CONCLUSION: Transparent film should be applied with care because of the high soil temperature stress. Black film and two-color film (silver on the front and black on the back) could be better option for rice yield, increasing and quality improving in a non-flooded condition. © 2023 Society of Chemical Industry.

Asporin inhibits collagen matrix-mediated intercellular mechanocommunications between fibroblasts during keloid progression.

Keloids are fibrotic lesions that grow unceasingly and invasively and are driven by local mechanical stimuli. Unlike other fibrotic diseases and normal wound healing, keloids exhibit little transformation of dermal fibroblasts into α-SMA+ myofibroblasts. This study showed that asporin is the most strongly expressed gene in keloids and its gene-ontology terms relate strongly to ECM metabolism/organization. Experiments with human dermal cells (HDFs) showed that asporin overexpression/treatment abrogated the HDF ability to adopt a perpendicular orientation when subjected to stretching tension. It also induced calcification of the surrounding 3D collagen matrix. Asporin overexpression/treatment also prevented the HDFs from remodeling the surrounding 3D collagen matrix, leading to a disorganized network of thick, wavy collagen fibers that resembled keloid collagen architecture. This in turn impaired the ability of the HDFs to contract the collagen matrix. Asporin treatment also made the fibroblasts impervious to the fibrous collagen contraction of α-SMA+ myofibroblasts, which normally activates fibroblasts. Thus, by calcifying collagen, asporin prevents fibroblasts from linearly rearranging the surrounding collagen; this reduces both their mechanosensitivity and mechanosignaling to each other through the collagen network. This blocks fibroblast activation and differentiation into the mature myofibroblasts that efficiently remodel the extracellular matrix. Consequently, the fibroblasts remain immature, highly proliferative, and continue laying down abundant extracellular matrix, causing keloid growth and invasion. Notably, dermal injection of asporin-overexpressing HDFs into murine wounds recapitulated keloid collagen histopathological characteristics. Thus, disrupted interfibroblast mechanocommunication may promote keloid progression. Asporin may be a new diagnostic biomarker and therapeutic target for keloids.

Role of Inflammasomes in Keloids and Hypertrophic Scars-Lessons Learned from Chronic Diabetic Wounds and Skin Fibrosis.

Keloids and hypertrophic scars are pathological cutaneous scars. They arise from excessive wound healing, which induces chronic dermal inflammation and results in overwhelming fibroblast production of extracellular matrix. Their etiology is unclear. Inflammasomes are multiprotein complexes that are important in proinflammatory innate-immune system responses. We asked whether inflammasomes participate in pathological scarring by examining the literature on scarring, diabetic wounds (also characterized by chronic inflammation), and systemic sclerosis (also marked by fibrosis). Pathological scars are predominantly populated by anti-inflammatory M2 macrophages and recent literature hints that this could be driven by non-canonical inflammasome signaling. Diabetic-wound healing associates with inflammasome activation in immune (macrophages) and non-immune (keratinocytes) cells. Fibrotic conditions associate with inflammasome activation and inflammasome-induced transition of epithelial cells/endothelial cells/macrophages into myofibroblasts that deposit excessive extracellular matrix. Studies suggest that mechanical stimuli activate inflammasomes via the cytoskeleton and that mechanotransduction-inflammasome crosstalk is involved in fibrosis. Further research should examine (i) the roles that various inflammasome types in macrophages, (myo)fibroblasts, and other cell types play in keloid development and (ii) how mechanical stimuli interact with inflammasomes and thereby drive scar growth. Such research is likely to significantly advance our understanding of pathological scarring and aid the development of new therapeutic strategies.

Degradation and Pathways of Carvone in Soil and Water.

Carvone is a monoterpene compound that has been widely used as a pesticide for more than 10 years. However, little is known regarding the fate of carvone, or its degradation products, in the environment. We used GC-MS (gas chromatography-mass spectrometry) to study the fate of carvone and its degradation and photolysis products under different soil and light conditions. We identified and quantified three degradation products of carvone in soil and water samples: dihydrocarvone, dihydrocarveol, and carvone camphor. In soil, dihydrocarveol was produced at very low levels (≤0.067 mg/kg), while dihydrocarvone was produced at much higher levels (≤2.07 mg/kg). In water exposed to differing light conditions, carvone was degraded to carvone camphor. The photolysis rate of carvone camphor under a mercury lamp was faster, but its persistence was lower than under a xenon lamp. The results of this study provide fundamental data to better understand the fate and degradation of carvone and its metabolites in the environment.

Systemic factors that shape cutaneous pathological scarring.

Cutaneous pathological scars are fibrotic lesions that grow continuously, invade the adjacent skin, and are erythematous, itchy, and painful. Their etiology remains unclear but may involve genetic, local mechanical, and systemic factors. Here, we will summarize the main systemic factors that shape cutaneous pathological scarring, especially keloid formation and aggravation. They include circulating cytokines, chemokines, growth factors, particular cell types, sex hormones, the systemic renin-angiotensin system, and vitamin D, all of which directly shape the angiogenesis, inflammation, fibrosis, and remodeling in pathological scars. There are also several environmental factors that more indirectly influence pathological scar formation or progression, namely diet, smoking, psychological stress, and exercise. Notably, much of the evidence on these systemic factors focus on their effects on one pathological scar characteristic, namely their fibrosis. However, systemic factors probably also shape other pathological scar characteristics. We describe two new avenues of keloid research that may greatly improve our understanding of pathological scarring and the systemic factors that affect it. One is the multiple similarities between keloids and tumors; the other is the different stem-cell populations in keloids. We expect this research will greatly aid the development of diagnostic biomarkers for cutaneous pathological scars and drugs/techniques/regimens that prevent, improve, or cure these scars.

Developing a Web-Based Shared Decision-Making Tool for Fertility Preservation Among Reproductive-Age Women With Breast Cancer: An Action Research Approach.

BACKGROUND: The pregnancy rate after cancer treatment for female survivors is lower than that of the general population. Future infertility is a significant concern for patients with breast cancer and is associated with a poor quality of life. Reproductive-age patients with breast cancer have safe options when choosing a type of fertility preservation method to be applied. Better information and support resources aimed at women to support their decision making are needed. OBJECTIVE: The objective of this study was to develop a web-based shared decision-making tool for helping patients with breast cancer make decisions on fertility preservation. METHODS: We used the action research cycle of observing, reflecting, planning, and acting to develop a web-based shared decision-making tool. The following four phrases were applied: (1) observe and reflect-collect and analyze the decision-making experiences of patients and health care providers; (2) reflect and plan-apply the initial results to create a paper design and modify the content; (3) plan and act-brainstorm about the web pages and modify the content; (4) act and observe-evaluate the effectiveness and refine the website's shared decision-making tool. Interviews, group meetings, and constant dialogue were conducted between the various participants at each step. Effectiveness was evaluated using the Preparation for Decision-Making scale. RESULTS: Five major parts were developed with the use of the action research approach. The Introduction (part 1) describes the severity of cancer treatment and infertility. Options (part 2) provides the knowledge of fertility preservation. The shared decision-making tool was designed as a step-by-step process (part 3) that involves the comparison of options, patient values, and preferences; their knowledge regarding infertility and options; and reaching a collective decision. Resources (part 4) provides information on the hospitals that provide such services, and References (part 5) lists all the literature cited in the website. The results show the web-based shared decision-making meets both patients' and health providers' needs and helps reproductive-age patients with breast cancer make decisions about fertility preservation. CONCLUSIONS: We have created the first web-based shared decision-making tool for making fertility preservation decisions in Taiwan. We believe female patients of reproductive age will find the tool useful and its use will become widespread, which should increase patient autonomy and improve communication about fertility preservation with clinicians. TRIAL REGISTRATION: Clinicaltrials.gov NCT04602910; https://clinicaltrials.gov/ct2/show/NCT04602910.

Reproductive outcomes of microdissection testicular sperm extraction in hypogonadotropic hypogonadal azoospermic men after gonadotropin therapy.

PURPOSE: Male infertility caused by hypogonadotropic hypogonadism (HH) is not common. The main treatment is gonadotropins for 12 months or longer. If the patient is still azoospermic, conventional or microdissection testicular sperm extraction (mTESE) may further help in sperm retrieval. We aimed to analyze the fertility outcomes of HH men treated at our institute. METHODS: From 2008 to 2020, infertile men with hormone profile showing HH were enrolled. Gonadotropin therapy was prescribed if parenthood was being considered. Assisted reproductive technology was available to help patients attain fertility depending on the results of sperm analysis. Patient outcomes, including sperm retrieval, pregnancy and live birth rates, were analyzed. RESULTS: Seventeen initially azoospermic patients were administered gonadotropins for an average of 11.1 months, and sperm was subsequently found in the ejaculate of seven patients (41%). mTESE was performed on the other ten (59%) who were still azoospermic. For these 10 patients, they had collectively undergone an average 12.1 months (range 6-23 months) of gonadotropin therapy. Sperm was retrieved in nine (90.0%) cases. After 11 cycles of TESE-ICSI, six (54.5%) successful pregnancies were recorded, resulting in five (55.6%) cases with live-born babies, including two sets of twins, and one case of missed abortion at 9 weeks of gestation. CONCLUSION: Gonadotropin therapy reversed azoospermia in a portion of the HH male patients studied. Of men who were still azoospermic after gonadotropin treatment, a majority could still have testicular sperm retrieved by mTESE for use in assisted reproductive technology, subsequently resulting in live births.

The Combined Application of Augmented Reality and Guide Template Technology in the Treatment of Nasal Deformities.

OBJECTIVE: The purpose of this study is to propose a surgical plan based on augmented reality (AR) and guide template technology for restoration of nasal deformities, and evaluate its feasibility and clinical efficacy. METHODS: Patients were scanned with a FaceScan to obtain the three-dimensional (3D) facial model, and computed tomography was also performed to obtain the maxillofacial computed tomography images while wearing the artificial marker. The mirroring tool and database searching and matching technology were employed to restore the nasal deformities for a normal nose (preoperative planning model). The design of guide template for deciding the incision area was based on the preoperative planning model, which was also imported into the AR image guidance system named HuaxiAR1.0 for reconstruction of the nose contour. One week after the surgery, the postoperative 3D facial model was obtained. Then, the clinical efficacy was evaluated by comparing the difference between the preoperative planning and postoperative 3D facial model. RESULTS: The patients obtained satisfactory nasal shapes after surgery. Comparison of the difference between the preoperative and postoperative 3D model revealed that the maximum error was ranging from 2.24 mm to 3.10 mm with the mean error from 0.54 mm to 0.65 mm. CONCLUSION: The combined application of AR and guide template technology provides a new approach for the treatment of nasal deformities, and has a certain significance in realizing the precise repair of other craniofacial soft tissue deformities.

Molecular Elucidation of a Urate Oxidase from Deinococcus radiodurans for Hyperuricemia and Gout Therapy.

Urate oxidase initiates the uric acid degradation pathways and is extensively used for protein drug development for gout therapy and serum uric acid diagnosis. We first present the biochemical and structural elucidation of a urate oxidase from the extremophile microorganism Deinococcus radiodurans (DrUox). From enzyme characterization, DrUox showed optimal catalytic ability at 30 °C and pH 9.0 with high stability under physiological conditions. Only the Mg2+ ion moderately elevated its activity, which indicates the characteristic of the cofactor-free urate oxidase family. Of note, DrUox is thermostable in mesophilic conditions. It retains almost 100% activity when incubated at 25 °C and 37 °C for 24 h. In this study, we characterized a thermostable urate oxidase, DrUox with high catalytic efficiency and thermal stability, which strengthens its potential for medical applications.

Sodium-glucose co-transporter-2 inhibitors and major adverse limb events: A trial-level meta-analysis including 51 713 individuals.

AIM: To analyse large-scale cardiovascular outcome trials of sodium-glucose co-transporter-2 (SGLT-2) inhibitors to evaluate whether there are safety concerns with respect to major adverse limb events overall or among various high-risk subgroups of patients. METHODS: We performed a quantitative meta-analysis of randomized, placebo-controlled, cardiovascular outcome trials of SGLT-2 inhibitors in patients with type 2 diabetes. We searched the PubMed, Embase and Cochrane databases for trials published up until 30 June 2020. The efficacy outcomes analysed included amputations and were stratified by several subgroup variables, including age, duration of diabetes, glucose control, renal function, established peripheral artery disease and diabetes microvascular complications. This review was registered before completing the analysis. RESULTS: Among 383 records identified, six studies assessing the following three SGLT-2 inhibitors met our inclusion criteria: empagliflozin (EMPA-REG OUTCOME study), canagliflozin (CANVAS Program and CREDENCE study), dapagliflozin (DECLARE-TIMI 58 and DAPA-HF trials) and ertugliflozin (VERTIS CV study). Of a total of 51 713 participants, 858 required amputation operations. The event rates of amputation were 2.0% (535/26 778) and 1.3% (323/24 927) in the SGLT-2 inhibitor and control groups, respectively. The random effects model revealed that SGLT-2 inhibitors were not significantly associated with an increased risk of amputation with substantial heterogeneity (pooled risk ratio, 1.24; 95% confidence interval, 0.96 to 1.60; I2 = 67.5%). This neutral effect of SGLT-2 inhibitors was also consistent across different levels of subgroups, including subgroups with or without established peripheral artery disease (PAD). CONCLUSIONS: SGLT-2 inhibitors are not associated with increased risks of amputation operations even among various high-risk subgroups, including patients with PAD. The amputation events primarily arise from critical limb ischaemia and infection instead of acute limb ischaemia. A multi-centre study focused on major adverse limb events with a longer follow-up is needed to confirm these results and provide guidelines for clinical practice.

Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes.

BACKGROUND: Spinal cord injury (SCI) is a catastrophic injury that can cause irreversible motor dysfunction with high disability. Exosomes participate in the transport of miRNAs and play an essential role in intercellular communication via transfer of genetic material. However, the miRNAs in exosomes which derived from neurons, and the underlying mechanisms by which they contribute to SCI remain unknown. METHODS: A contusive in vivo SCI model and a series of in vitro experiments were carried out to explore the therapeutic effects of exosomes. Then, a miRNA microarray analysis and rescue experiments were performed to confirm the role of neuron-derived exosomal miRNA in SCI. Western blot, luciferase activity assay, and RNA-ChIP were used to investigate the underlying mechanisms. RESULTS: The results indicated that neuron-derived exosomes promoted functional behavioral recovery by suppressing the activation of M1 microglia and A1 astrocytes in vivo and in vitro. A miRNA array showed miR-124-3p to be the most enriched in neuron-derived exosomes. MYH9 was identified as the target downstream gene of miR-124-3p. A series of experiments were used to confirm the miR-124-3p/MYH9 axis. Finally, it was found that PI3K/AKT/NF-κB signaling cascades may be involved in the modulation of microglia by exosomal miR-124-3p. CONCLUSION: A combination of miRNAs and neuron-derived exosomes may be a promising, minimally invasive approach for the treatment of SCI.

Augmented Reality Technology Could Be an Alternative Method to Treat Craniomaxillofacial Foreign Bodies: A Comparative Study Between Augmented Reality Technology and Navigation Technology.

PURPOSE: Removal of foreign bodies in the craniomaxillofacial region can be challenging. The purpose of the present study was to explore the feasibility of using augmented reality (AR) technology to remove craniomaxillofacial foreign bodies. PATIENTS AND METHODS: A prospective study of patients with granular metal foreign bodies retained in the craniomaxillofacial region from March 2017 to March 2019 was performed. AR technology and navigation technology were both used to localize the foreign bodies. The face was divided into upper and lower parts by the ala-tragus line. In groups A and B, navigation technology was used to locate the foreign bodies in the upper face and lower face, respectively. Similarly, AR technology was used in the upper face and lower face in groups C and D, respectively. The primary predictor variable was the technology type. The primary outcome variables were the positioning deviation and the time required for surface positioning. The paired t test and independent samples t test were used for statistical analysis. RESULTS: Five patients with 24 craniomaxillofacial foreign bodies were included in the present study. The positioning deviation with navigation technology (1.42 ± 0.49 mm) did not differ from that with AR technology (1.52 ± 0.58 mm; P = .116). The positioning deviation of groups A, B, C, and D was 1.01 ± 0.37, 1.73 ± 0.29, 1.02 ± 0.44, and 1.89 ± 0.36 mm, respectively. The differences for groups A and B were statistically significant (P < .01), as were the differences for groups C and D (P < .01). The time required to position the 2 technologies was significantly different (10.04 ± 2.88 seconds for navigation technology and 3.46 ± 0.83 seconds for AR technology; P < .01). CONCLUSIONS: AR technology positioning was similar to that of navigation technology; however, it does not require an invasive registration device and provides real-time dynamic image guidance. AR technology could be an alternative method for treating foreign bodies in the craniomaxillofacial region.

The Vascular Involvement in Soft Tissue Fibrosis-Lessons Learned from Pathological Scarring.

Soft tissue fibrosis in important organs such as the heart, liver, lung, and kidney is a serious pathological process that is characterized by excessive connective tissue deposition. It is the result of chronic but progressive accumulation of fibroblasts and their production of extracellular matrix components such as collagens. Research on pathological scars, namely, hypertrophic scars and keloids, may provide important clues about the mechanisms that drive soft tissue fibrosis, in particular the vascular involvement. This is because these dermal fibrotic lesions bear all of the fibrotic characteristics seen in soft tissue fibrosis. Moreover, their location on the skin surface means they are readily observable and directly treatable and therefore more accessible to research. We will focus here on the roles that blood vessel-associated cells play in cutaneous scar pathology and assess from the literature whether these cells also contribute to other soft tissue fibroses. These cells include endothelial cells, which not only exhibit aberrant functions but also differentiate into mesenchymal cells in pathological scars. They also include pericytes, hepatic stellate cells, fibrocytes, and myofibroblasts. This article will review with broad strokes the roles that these cells play in the pathophysiology of different soft tissue fibroses. We hope that this brief but wide-ranging overview of the vascular involvement in fibrosis pathophysiology will aid research into the mechanisms underlying fibrosis and that this will eventually lead to the development of interventions that can prevent, reduce, or even reverse fibrosis formation and/or progression.