Construction of the single-diamond-structured titania scaffold-Recreation of the holy grail photonic structure.

As one of the most stunning biological nanostructures, the single-diamond (SD) surface discovered in beetles and weevils exoskeletons possesses the widest complete photonic bandgap known to date and is renowned as the "holy grail" of photonic materials. However, the synthesis of SD is difficult due to its thermodynamical instability compared to the energetically favoured bicontinuous double diamond and other easily formed lattices; thus, the artificial fabrication of SD has long been a formidable challenge. Herein, we report a bottom-up approach to fabricate SD titania networks via a one-pot cooperative assembly scenario employing the diblock copolymer poly(ethylene oxide)-block-polystyrene as a soft template and titanium diisopropoxide bis(acetylacetonate) as an inorganic precursor in a mixed solvent, in which the SD scaffold was obtained by kinetically controlled nucleation and growth in the skeletal channels of the diamond minimal surface formed by the polymer matrix. Electron crystallography investigations revealed the formation of tetrahedrally connected SD frameworks with the space group Fd [Formula: see text] m in a polycrystalline anatase form. A photonic bandgap calculation showed that the resulting SD structure has a wide and complete bandgap. This work solves the complex synthetic enigmas and offers a frontier in hyperbolic surfaces, biorelevant materials, next-generation optical devices, etc.

ETS1 Deficiency in Macrophages Suppresses Colorectal Cancer Progression by Reducing the F4/80+TIM4+ Macrophage Population.

Tumor-associated macrophages (TAMs) take on pivotal and complex roles in the tumor microenvironment (TME); however, their heterogeneity in the TME remains incompletely understood. ETS proto-oncogene 1 (ETS1) is a transcription factor that is mainly expressed in lymphocytes. However, its expression and immunoregulatory role in colorectal cancer (CRC)-associated macrophages remain unclear. In the study, the expression levels of ETS1 in CD68+ macrophages in the CRC microenvironment were significantly higher than those in matched para-carcinoma tissues. Importantly, ETS1 increased the levels of chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) in lipopolysaccharide-stimulated THP-1 cells. It also boosted the migration and invasion of CRC cells during the in vitro co-culture. In ETS1 conditional knockout mouse model, ETS1 deficiency in macrophages ameliorated the histological changes in DSS-induced ulcerative colitis mouse models and prolonged the survival in an azomethane/dextran sodium sulfate (AOM/DSS)-induced CRC model. ETS1 deficiency in macrophages substantially inhibited tumor formation, reduced F4/80+TIM4+ macrophages in the mesenteric lymph nodes, and decreased CCL2 and CXCL10 protein levels in tumor tissues. Moreover, ETS1 deficiency in macrophages effectively prevented liver metastasis of CRC and reduced the infiltration of TAMs into the metastasis sites. Subsequent studies have indicated that ETS1 upregulated the expression of T-cell immunoglobulin mucin receptor 4 in macrophages through the signal transducer and activator of transcription 1 signaling pathway activated by the autocrine action of CCL2/CXCL10. Collectively, ETS1 deficiency in macrophages potentiates antitumor immune responses by repressing CCL2 and CXCL10 expression, shedding light on potential therapeutic strategies for CRC.

Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: the role of mitochondrial damage.

Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates procellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

Trifunctional Nanocomposites with Colorimetric Magnetic Catalytic Activities Labels in Sandwich Immunochromatographic Detection of Escherichia coli O157:H7.

The emergence of nanoenzymes has catalyzed the robust advancement of the lateral flow immunoassay (LFIA) in recent years. Among them, multifunctional nanocomposite enzymes with core-shell architectures are considered preferable for promoting the sensing ability due to their good biocompatibility, precise control over size, and surface properties etc. Herein, we developed a dual-channel ensured lateral flow immunoassay (DFLIA) platform utilizing a magnetic, colorimetric, and catalytic multifunctional nanocomposite enzyme (Fe3O4@TCPP@Pd) [TCPP, Tetrakis (4-carboxyphenyl) porphyrin] for the ultrasensitive and highly accurate rapid detection of Escherichia coli O157:H7 (E. coli O157:H7). Fe3O4@TCPP@Pd-mAb exhibits superior performance compared to traditional AuNPs, including enhanced sensitivity and an extended linear detection range, benefiting from its high brightness signal, strong magnetic separation ability, and high peroxidase activity (Vmax = 2.32 µM S1-). Moreover, the Fe3O4@TCPP@Pd-labeled mAb probe exhibited exceptional stability and high affinity toward E. coli O157:H7 (with an affinity constant of approximately 1.723 × 109 M-1), indicating its potential for the efficient capture of the pathogen. Impressively, the developed Fe3O4@TCPP@Pd-DFLIA achieved ultrasensitive detection for E. coli O157:H7 with pre- and postcatalytic naked-eye detection sensitivities of 255 cfu/mL and 77 cfu/mL, respectively, representing an approximately 41-fold improvement over the conventional AuNP-based LFIA and also possessed good specificity and reproducibility [relative standard deviation (RSD) < 10%]. Additionally, the established DFLIA exhibited satisfactory recoveries in detecting pork and milk samples, further validating the reliability of this platform for immunoassays and demonstrating its potential for utilization in bioassays and clinical diagnostics.

"Three-in-One" Multifunctional Hollow Nanocages with Colorimetric Photothermal Catalytic Activity for Enhancing Sensitivity in Biosensing.

Immunochromatographic assays (ICAs) have been widely used in the field detection of mycotoxin contaminants. Nevertheless, the lack of multisignal readout capability and the ability of signaling tags to maintain their biological activity while efficiently loading antibodies remain a great challenge in satisfying diverse testing demands. Herein, we proposed a novel three-in-one multifunctional hollow vanadium nanomicrosphere (high brightness-catalytic-photothermal properties)-mediated triple-readout ICA (VHMS-ICA) for sensitive detection of T-2. As the key to this biosensing strategy, vanadium was used as the catalytic-photothermal characterization center, and natural polyphenols were utilized as the bridging ligands for coupling with the antibody while self-assembling with formaldehyde cross-linking into a hollow nanocage-like structure, which offers the possibility of realizing a three-signal readout strategy and improving the coupling efficiency to the antibody while preserving its biological activity. The constructed sensors showed a detection limit (LOD) of 2 pg/mL for T-2, which was about 345-fold higher than that of conventional gold nanoparticle-based ICA (0.596 ng/mL). As anticipated, the detection range of VHMS-ICA was extended about 8-fold compared with the colorimetric signal alone. Ultimately, the proposed immunosensor performed well in maize and oat samples, with satisfactory recoveries. Owing to the synergistic and complementary interactions between distinct signaling modes, the establishment of multimodal immunosensors with multifunctional tags is an efficient strategy to satisfy diversified detection demands.

Modeling evolution of cell morphology under stretching.

The mechanical stimulation of cells from the surrounding environment is an important life activity. However, there has been a lack of dynamically quantitative analysis of cell morphology under mechanical stimulations. A theoretical model for the evolution of cell morphology under stretching is proposed by analyzing the transformation between cell deformation energy and adhesion energy. The images of the evolution show that detachment of the adhesion membrane or re-adhesion of the cell, causes a decrease or increase of the adhesion area, respectively. In addition to the stretching amplitude and velocity, we found that the duration of the stretching stage and the no stretching stage can affect the cell morphology during cyclic stretching. The theoretical model explains some counter-intuitive experimental results and provides many quantitative insights into understanding the physical mechanisms of cell adhesion under stretching. This study can provide a useful guide to control cell adhesion under mechanical stimulations.

Aerobic exercise training engages the canonical wnt pathway to improve pulmonary function and inflammation in COPD.

BACKGROUND: We studied whether the exercise improves cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) in mice through inhibition of inflammation mediated by Wnt/ß-catenin-peroxisome proliferator-activated receptor (PPAR) γ signaling. METHODS: Firstly, we observed the effect of exercise on pulmonary inflammation, lung function, and Wnt/ß-catenin-PPARγ. A total of 30 male C57BL/6J mice were divided into the control group (CG), smoke group (SG), low-intensity exercise group (LEG), moderate-intensity exercise group (MEG), and high-intensity exercise group (HEG). All the groups, except for CG, underwent whole-body progressive exposure to CS for 25 weeks. Then, we assessed the maximal exercise capacity of mice from the LEG, MEG, and HEG, and performed an 8-week treadmill exercise intervention. Then, we used LiCl (Wnt/ß-catenin agonist) and XAV939 (Wnt/ß-catenin antagonist) to investigate whether Wnt/ß-catenin-PPARγ pathway played a role in the improvement of COPD via exercise. Male C57BL/6J mice were randomly divided into six groups (n = 6 per group): CG, SG, LiCl group, LiCl and exercise group, XAV939 group, and XAV939 and exercise group. Mice except those in the CG were exposed to CS, and those in the exercise groups were subjected to moderate-intensity exercise training. All the mice were subjected to lung function test, lung histological assessment, and analysis of inflammatory markers in the bronchoalveolar lavage fluid, as well as detection of Wnt1, ß-catenin and PPARγ proteins in the lung tissue. RESULTS: Exercise of various intensities alleviated lung structural changes, pulmonary function and inflammation in COPD, with moderate-intensity exercise exhibiting significant and comprehensive effects on the alleviation of pulmonary inflammation and improvement of lung function. Low-, moderate-, and high-intensity exercise decreased ß-catenin levels and increased those of PPARγ significantly, and only moderate-intensity exercise reduced the level of Wnt1 protein. Moderate-intensity exercise relieved the inflammation aggravated by Wnt agonist. Wnt antagonist combined with moderate-intensity exercise increased the levels of PPARγ, which may explain the highest improvement of pulmonary function observed in this group. CONCLUSIONS: Exercise effectively decreases COPD pulmonary inflammation and improves pulmonary function. The beneficial role of exercise may be exerted through Wnt/ß-catenin-PPARγ pathway.

Investigation of clinical significance of ST-segment depression during paroxysmal supraventricular tachycardia.

INTRODUCTION: There are great differences in ST-segment depression during PSVT episodes. The aim of this study is to investigate the clinical significance of ST segment depression during PSVT. METHODS: The study enrolled 333 consecutive patients who were diagnosed with PSVT by electrophysiological test from Jan 1, 2021 to July 31, 2022. The range, magnitude and morphology of ST-segment depression were described. The correlation between ST-segment depression and symptoms of chest tightness, chest pain or hypotension, the correlation between ST-segment depression and coronary stenosis, and the possible influencing factors were analyzed. In addition, the diagnostic efficacy of ST-segment depression for AVRT was determined. RESULTS: ST-segment depression was present in 85% of patients, in 70% of which the depression range was more than six leads. The magnitude of the depression was more significant in precordial leads (P < 0.001). ST-segment depression of >1 mm in limb leads and precordial leads was found in 36.0% and 49.8% of the patients, respectively, while >3 mm was found in 2.4% and 9.6%, respectively. The morphology of ST-segment depression in limb leads was different from that in precordial leads (P < 0.001). Downsloping ST-segment depression was more common in limb leads (limb vs. precordial: 40.5% vs. 12.6%), whereas upsloping depression was more common in precordial leads (limb vs. precordial: 3.0% vs. 23.1%). Correlation analysis showed that ST-segment depression was not correlated with symptoms of chest tightness and pain, nor was it correlated with coronary artery stenosis. The most important influencing factor is the type of PSVT, especially affecting the morphology of depression in limb leads (OR = 10.27 [5.93-17.79], P < 0.001). The sensitivity and specificity of downsloping ST-segment depression in limb leads for diagnosis of AVRT were 75.5% and 76.7%. CONCLUSION: ST-segment depression is a common ECG change during PSVT episodes, and it's not associated with severe coronary stenosis. The type of PSVT has a significant effect on the manifestation of ST-segment depression. The downslope morphology of ST-segment depression in limb leads is helpful in differentiating AVRT from AVNRT.

The Relationships Among Family Functioning, Sleep Quality and Quality of Life in Chinese Community-Dwelling Older Adults with Insomnia: A Structural Equation Model.

OBJECTIVES: The proportion of individuals with insomnia is increasing, and many older adults have insomnia. This study aimed to explore the relationships between family functioning and quality of life (QOL) among community-dwelling older adults with insomnia, as well as to explore the mediating role of sleep quality in this relationship. METHODS: The participants were 225 older adults with insomnia from community health service centers in Chongqing, China. The Family Care Index (APGAR) was used to assess family functioning, the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, and the 36-item Short-Form Health Survey (SF-36) was used to assess QOL. RESULTS: The results showed that family functioning would be positively associated with QOL (p = .005) and that this relationship would be partially mediated by higher sleep quality (p < .001). CONCLUSIONS: Family functioning has a direct effect on QOL and an indirect effect on QOL through the regulation of sleep quality. Maintaining good family functioning is important for improving sleep quality and QOL in older adults with insomnia. CLINICAL IMPLICATIONS: Developing family functioning-based assessments and targeted intervention strategies could be beneficial for older adults with insomnia.

ASD-SWNet: a novel shared-weight feature extraction and classification network for autism spectrum disorder diagnosis.

The traditional diagnostic process for autism spectrum disorder (ASD) is subjective, where early and accurate diagnosis significantly affects treatment outcomes and life quality. Thus, improving ASD diagnostic methods is critical. This paper proposes ASD-SWNet, a new shared-weight feature extraction and classification network. It resolves the issue found in previous studies of inefficiently integrating unsupervised and supervised learning, thereby enhancing diagnostic precision. The approach utilizes functional magnetic resonance imaging to improve diagnostic accuracy, featuring an autoencoder (AE) with Gaussian noise for robust feature extraction and a tailored convolutional neural network (CNN) for classification. The shared-weight mechanism utilizes features learned by the AE to initialize the convolutional layer weights of the CNN, thereby integrating AE and CNN for joint training. A novel data augmentation strategy for time-series medical data is also introduced, tackling the problem of small sample sizes. Tested on the ABIDE-I dataset through nested ten-fold cross-validation, the method achieved an accuracy of 76.52% and an AUC of 0.81. This approach surpasses existing methods, showing significant enhancements in diagnostic accuracy and robustness. The contribution of this paper lies not only in proposing new methods for ASD diagnosis but also in offering new approaches for other neurological brain diseases.

Mutual regulations between Toxoplasma gondii and type I interferon.

In the decades since the discovery, Type I interferon (IFN-I) has been intensively studied for their antiviral activity. However, increasing evidences suggest that it may also play an important role in the infection of Toxoplasma gondii, a model organism for intracellular parasites. Recent studies demonstrated that the induction of IFN-I by the parasite depends on cell type, strain genotype, and mouse strain. IFN-I can inhibit the proliferation of T. gondii, but few studies showed that it is beneficial to the growth of the parasite. Meanwhile, T. gondii also can secrete proteins that impact the pathway of IFN-I production and downstream induced interferon-stimulated genes (ISGs) regulation, thereby escaping immune destruction by the host. This article reviews the major findings and progress in the production, function, and regulation of IFN-I during T. gondii infection, to thoroughly understand the innate immune mechanism of T. gondii infection, which provides a new target for subsequent intervention and treatment.

Effect of Rectus Sheath Block on Postoperative Quality of Recovery After Transabdominal Midline Gynecological Surgery: A Randomized Controlled Trial.

Introduction: Rectus sheath block is an emerging technique that provide effective perioperative analgesia and is related to lower perioperative opioid consumption and decrease opioid-related adverse effects. The present research is designed to explore the effect of rectus sheath block on recovery quality in patients following transabdominal midline gynecological surgery. Methods: Ninety female patients following elective transabdominal midline gynecological surgery were enrolled. Patients were randomized to group R (n = 45) which receive preoperative ultrasound-guided RSB with 0.4% ropivacaine or group C which is control group (n = 45). The primary outcome was the quality of recovery on the first postoperative day. The quality of recovery was assessed by the 40-item Quality of Recovery questionnaire (QoR-40). Secondary outcomes included the intraoperative opioid consumption, time to first flatus and time to first discharging from bed, postoperative nausea and vomiting, and patient satisfaction. Results: The patients in two groups had comparable baseline characteristics. Postoperative global QoR-40 scores were significantly better in group R than in group C (165.0[159.5-170.0] vs 155.0[150.0-157.0], respectively; median difference 12[95% confidence interval: 8-15, P<0.001]). Preoperative RSB reduced intraoperative opioid consumption, reduced the time to first flatus, time to first discharging from bed and the post anaesthesia care unit discharge time. Furthermore, group R showed greater patient satisfaction. Conclusion: A single preoperative administration of RSB with ropivacaine improved the quality of recovery in patients following transabdominal midline gynecological surgery.

Although laparoscopic surgery accounts for a higher proportion of gynecological procedures, open gynecological surgery remains irreplaceable for some patients. Recovery from open gynecological surgery is a combination of physical injuries and psychological challenges. Consequently, accelerating functional recovery, alleviating discomfort and improving the quality of recovery in such patients is a clinical issue that we need to focus on. The QoR 40 scale is a patient-reported assessment tool which evaluates the quality of recovery in five dimensions. Ultrasound-guided rectus sheath block is a safe and effective abdominal wall nerve block for anesthesia and analgesia of umbilical and median abdominal longitudinal incisions. This study investigated the impact of rectus sheath block on the quality of postoperative recovery after open gynecological surgery using the QoR40 scale. Participants were randomized to two groups: rectus sheath block treatments and a control group receiving standard care only. Rectus sheath block improves the quality of recovery in patients undergoing open gynecological surgery one day after surgery without adverse effects, which has successfully made rapid rehabilitation from bench to bedside.

Designing Low Toxic Deep Eutectic Solvents for the Green Recycle of Lithium-Ion Batteries Cathodes.

The Lithium-ion battery (LIB) is one of the main energy storage equipment. Its cathode material contains Li, Co, and other valuable metals. Therefore, recycling spent LIBs can reduce environmental pollution and resource waste, which is significant for sustainable development. However, traditional metallurgical methods are not environmentally friendly, with high cost and environmental toxicity. Recently, the concept of green chemistry gives rise to environmental and efficient recycling technology, which promotes the transition of recycling solvents from organic solvents to green solvents represented by deep eutectic solvents (DESs). DESs are considered as ideal alternative solvents in extraction processes, attracting great attention due to their low cost, low toxicity, good biodegradability, and high extraction capacity. It is very important to develop the DESs system for LIBs recycling for sustainable development of energy and green economic development of recycling technology. In this work, the applications and research progress of DESs in LIBs recovery are reviewed, and the physicochemical properties such as viscosity, toxicity and regulatory properties are summarized and discussed. In particular, the toxicity data of DESs are collected and analyzed. Finally, the guidance and prospects for future research are put forward, aiming to explore more suitable DESs for recycling valuable metals in batteries.

The effects of combining visual-auditory stimuli with exercise on short-term affect improvement: a randomized controlled trial.

ABSTRAC T: Prior research has explored the effects of engaging with real or virtual natural landscapes and listening to music during aerobic exercise on short-term affect, however, the specific differences in the improvement of short-term affect by different combinations of Virtual Reality (VR) and music rhythm require further investigation. The objective of this study is to investigate the effects of various combinations of VR and music on short-term mood, thereby providing a reference for future research on public fitness. This study recruited 132 valid participants (mean age 24.0 ± 0.9 years), with a gender distribution of 68 males and 64 females. Participants were randomly assigned to one of four groups: Visual-Music (V-M), Music-Visual (M-V), Visual-only (V), and Music-only (M). The exercise mode was 15 min of aerobic power cycling with 2 min of low-intensity power cycling intervals in the middle. After the exercise, the participants were asked to sit and then performed either a VR intervention or a music intervention for 15 min. The collected indicators included blood pressure, positive/negative affect, and heart rate variability indicators (RMSSD, SDNN, LF/HF). Data analysis included descriptive statistics, repeated measures ANOVA, and multifactor ANOVA. The effect of different VR and Music combined with exercise interventions on the improvement of short-term affect was analyzed based on the effect size (ɳp2) and combined with the significance p-value. Intra-group results showed that DBP, positive and negative affect, SDNN, RMSSD indicators in V-M group were significant differences (p < 0.05), while SBP, positive affect, negative affect, SDNN, RMSSD, LF/HF indicators in M-V group were significant differences (p < 0.05). Only SDNN and RMSSD indicators in M group had significant differences (p < 0.05), and only SBP and RMSSD indicators in V group had significant differences (p < 0.05). The results between groups showed that only SDNN and LH/HF groups had a significant difference (p < 0.05), other indicators had a trend of improvement or positive promotion to a certain extent, but the statistical difference was not significant (p > 0.05). Aerobic exercise with consistent intensity and the combined visual-auditory interventions (M-V and V-M) significantly improved blood pressure, and the short-term affect of physiological responses (LF/HF, SDNN, RMSSD), along with subjective affect measures, compared to other groups. These findings suggest that incorporating VR and music with exercise can effectively enhance short-term affect, recommending an integrated approach to aerobic exercise and relaxation through music and visual exposure to natural environments.

Manganese-based nanomaterials promote synergistic photo-immunotherapy: green synthesis, underlying mechanisms, and multiple applications.

Single phototherapy and immunotherapy have individually made great achievements in tumor treatment. However, monotherapy has difficulty in balancing accuracy and efficiency. Combining phototherapy with immunotherapy can realize the growth inhibition of distal metastatic tumors and enable the remote monitoring of tumor treatment. The development of nanomaterials with photo-responsiveness and anti-tumor immunity activation ability is crucial for achieving photo-immunotherapy. As immune adjuvants, photosensitizers and photothermal agents, manganese-based nanoparticles (Mn-based NPs) have become a research hotspot owing to their multiple ways of anti-tumor immunity regulation, photothermal conversion and multimodal imaging. However, systematic studies on the synergistic photo-immunotherapy applications of Mn-based NPs are still limited; especially, the green synthesis and mechanism of Mn-based NPs applied in immunotherapy are rarely comprehensively discussed. In this review, the synthesis strategies and function of Mn-based NPs in immunotherapy are first introduced. Next, the different mechanisms and leading applications of Mn-based NPs in immunotherapy are reviewed. In addition, the advantages of Mn-based NPs in synergistic photo-immunotherapy are highlighted. Finally, the challenges and research focus of Mn-based NPs in combination therapy are discussed, which might provide guidance for future personalized cancer therapy.

Cell sheet formation enhances the therapeutic effects of adipose-derived stromal vascular fraction on urethral stricture.

Urethral stricture (US) is a common disease in urology, lacking effective treatment options. Although injecting a stem cells suspension into the affected area has shown therapeutic benefits, challenges such as low retention rate and limited efficacy hinder the clinical application of stem cells. This study evaluates the therapeutic impact and the mechanism of adipose-derived vascular fraction (SVF) combined with cell sheet engineering technique on urethral fibrosis in a rat model of US. The results showed that SVF-cell sheets exhibit positive expression of α-SMA, CD31, CD34, Stro-1, and eNOS. In vivo study showed less collagen deposition, low urethral fibrosis, and minimal tissue alteration in the group receiving cell sheet transplantation. Furthermore, the formation of a three-dimensional (3D) tissue-like structure by the cell sheets enhances the paracrine effect of SVF, facilitates the infiltration of M2 macrophages, and suppresses the TGF-ß/Smad2 pathway through HGF secretion, thereby exerting antifibrotic effects. Small animal in vivo imaging demonstrates improved retention of SVF cells at the damaged urethra site with cell sheet application. Our results suggest that SVF combined with cell sheet technology more efficiently inhibits the early stages of urethral fibrosis.

Mitochondrial activity related genes of mast cells identify poor prognosis and metastasis of ovarian cancer.

The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor progression, but also on their location in the tumor bulk. In our investigation, we employed immunohistochemistry to reveal that the mast cells (MCs) in the tumor stroma are positively correlated with metastasis of ovarian cancer (OC), but not in the tumor parenchyma. To delve deeper into the influence of different culture matrix stiffness on MCs' biological functions within the tumor parenchymal and stromal regions, we conducted a transcriptome analysis of the mouse MC line (P815) cultured in two-dimensional (2D) or three-dimensional (3D) culture system. Further research has found that the softer 3D extracellular matrix stiffness could improve the mitochondrial activity of MCs to promote proliferation by increasing the expression levels of mitochondrial activity-related genes, namely Pet100, atp5md, and Cox7a2. Furthermore, employing LASSO regression analysis, we identified that Pet100 and Cox7a2 were closely associated with the prognosis of OC patients. These two genes were subsequently employed to construct a risk score model, which revealed that the high-risk group model as one of the prognostic factors for OC patients. Additionally, the XCell algorithm analysis showed that the high-risk group displayed a broader spectrum of immune cell infiltrations. Our research revealed that TIMs in the tumor stroma could promote the metastasis of OC, and mitochondrial activity-related proteins Pet100/Cox7a2 can serve as biomarkers for prognostic evaluation of OC.

Exercise Attenuate Diaphragm Atrophy in COPD Mice via Inhibiting the RhoA/ROCK Signaling.

Background: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear. Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1ß, TNF-α, and RhoA/ROCK were determined by Western blotting. Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably. Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.

FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer.

Programmed cell death 1 ligand 1 (PDL1)/programmed cell death 1 (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on the effectiveness of the treatment are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response in macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed in malignant cells in the CRC microenvironment, notably, the expression level of FSTL3 was related to tumor immune evasion and the clinical efficacy of anti-PD1 therapy. Further studies determined that hypoxic tumor microenvironment induced the FSTL3 expression via HIF1α in CRC cells, FSTL3 could bind to the transcription factor c-Myc (354-406 amino acids) to suppress the latter's ubiquitination and increase its stability, thereby to up-regulated the expression of PDL1 and indoleamine 2,3-dioxygenase 1 (IDO1). The results in the immunocompetent tumor models verified that FSLT3 knockout in tumor cells increased the proportion of CD8+ T cells in the tumor microenvironment, reduced the proportion of regulatory T cells (CD25+ Foxp3+) and exhausted T cells (PD1+ CD8+), and synergistically improved the anti-PD1 therapy efficacy. To sum up, FSTL3 enhanced c-Myc-mediated transcriptional regulation to promote immune evasion and attenuates response to anti-PD1 therapy in CRC, suggesting the potential of FSTL3 as a biomarker of immunotherapeutic efficacy as well as a novel immunotherapeutic target in CRC.

Development and validation of a novel nomogram model to assess the risk of gastric contents in outpatients undergoing elective sedative gastrointestinal endoscopy procedures.

BACKGROUND: Gastric contents may contribute to patients' aspiration during anesthesia. Ultrasound can accurately assess the risk of gastric contents in patients undergoing sedative gastrointestinal endoscopy (GIE) procedures, but its efficiency is limited. Therefore, developing an accurate and efficient model to predict gastric contents in outpatients undergoing elective sedative GIE procedures is greatly desirable. METHODS: This study retrospectively analyzed 1501 patients undergoing sedative GIE procedures. Gastric contents were observed under direct gastroscopic vision and suctioned through the endoscope. High-risk gastric contents were defined as having solid content or liquid volume > 25 ml and pH < 2.5; otherwise, they were considered low-risk gastric contents. Univariate analysis and multivariate analysis were used to select the independent risk factors to predict high-risk gastric contents. Based on the selected independent risk factors, we assigned values to each independent risk factor and established a novel nomogram. The performance of the nomogram was verified in the testing cohort by the metrics of discrimination, calibration, and clinical usefulness. In addition, an online accessible web calculator was constructed. RESULTS: We found BMI, cerebral infarction, cirrhosis, male, age, diabetes, and gastroesophageal reflux disease were risk factors for gastric contents. The AUROCs were 0.911 and 0.864 in the development and testing cohort, respectively. Moreover, the nomogram showed good calibration ability. Decision curve analysis and Clinical impact curve demonstrated that the predictive nomogram was clinically useful. The website of the nomogram was https://medication.shinyapps.io/dynnomapp/. CONCLUSIONS: This study demonstrates that clinical variables can be combined with algorithmic techniques to predict gastric contents in outpatients. Nomogram was constructed from routine variables, and the web calculator had excellent clinical applicability to assess the risk of gastric contents accurately and efficiently in outpatients, assist anesthesiologists in assessment and identify the most appropriate patients for ultrasound.