Competing C and N as Reactive Centers for Microsolvated Ambident Nucleophiles CN-(H2O)n=0-3: A Theoretical Study of E2/SN2 Reactions with CH3CH2X (X = Cl, Br, I).

As an ambident nucleophile, CN- has both C and N atoms that can act as the reactive center to facilitate substitution reactions. We investigate in detail the potential energy profiles of CN-(H2O)0-3 with CH3CH2X (X = Cl, Br, I) to explore the influence of solvent molecules on competition between the different nucleophilic atoms C and N involving the SN2 and E2 pathways. The energy barrier sequence for the transition states follows C@inv-SN2 < N@inv-SN2 < C@anti-E2 < N@anti-E2. When two different atoms act as nucleophilic atoms, the SN2 reaction is always preferred over the E2 reaction, and this preference increases with microsolvation. For the ambident nucleophiles CN-(H2O)0-3, C as the reactive center always has stronger nucleophilicity and basicity than N acting as the reactive center. Regarding the leaving group, the height of the energy barrier is positively correlated with the acidity of the CH3CH2X substrate for the E2 pathway and with X-heterolysis for the SN2 pathway. Furthermore, we found that in the gas phase, the energy barrier for different leaving group systems decreases gradually in the order Cl > Br > I, while in the SMD solution, the energy barrier and product energy increase slightly in the system from X = Cl to Br; this change may be due to the significantly weakened transition-state interaction for the X = Br system. Our activation strain, quantitative molecular orbital, and charge analyses reveal the physical mechanisms underlying the various computed trends. In addition, we also demonstrate the two points recently proposed by Vermeeren, P. . Chem. Eur. J. 2020, 26, 15538-15548.

Programmable ultrasound imaging guided theranostic nanodroplet destruction for precision therapy of breast cancer.

Ultrasound-stimulated contrast agents have gained significant attention in the field of tumor treatment as drug delivery systems. However, their limited drug-loading efficiency and the issue of bulky, imprecise release have resulted in inadequate drug concentrations at targeted tissues. Herein, we developed a highly efficient approach for doxorubicin (DOX) precise release at tumor site and real-time feedback via an integrated strategy of "programmable ultrasonic imaging guided accurate nanodroplet destruction for drug release" (PND). We synthesized DOX-loaded nanodroplets (DOX-NDs) with improved loading efficiency (15 %) and smaller size (mean particle size: 358 nm). These DOX-NDs exhibited lower ultrasound activation thresholds (2.46 MPa). By utilizing a single diagnostic transducer for both ultrasound stimulation and imaging guidance, we successfully vaporized the DOX-NDs and released the drug at the tumor site in 4 T1 tumor-bearing mice. Remarkably, the PND group achieved similar tumor remission effects with less than half the dose of DOX required in conventional treatment. Furthermore, the ultrasound-mediated vaporization of DOX-NDs induced tumor cell apoptosis with minimal damage to surrounding normal tissues. In summary, our PND strategy offers a precise and programmable approach for drug delivery and therapy, combining ultrasound imaging guidance. This approach shows great potential in enhancing tumor treatment efficacy while minimizing harm to healthy tissues.

Transparent Self-Healing Anti-Freezing Ionogel for Monolayered Triboelectric Nanogenerator and Electromagnetic Energy-Based Touch Panel.

The advent of Internet of Things and artificial intelligence era necessitates the advancement of self-powered electronics. However, prevalent multifunctional electronics still face great challenges in rigid electrodes, stacked layers, and external power sources to restrict the development in flexible electronics. Here, a transparent, self-healing, anti-freezing (TSA) ionogel composed of fluorine-rich ionic liquid and fluorocarbon elastomer, which is engineered for monolayered triboelectric nanogenerators (M-TENG) and electromagnetic energy-based touch panels is developed. Notably, the TSA-ionogel exhibits remarkable features including outstanding transparency (90%), anti-freezing robustness (253 K), impressive stretchability (600%), and repetitive self-healing capacity. The resultant M-TENG achieves a significant output power density (200 mW m-2 ) and sustains operational stability beyond 1 year. Leveraging this remarkable performance, the M-TENG is adeptly harnessed for biomechanical energy harvesting, self-powered control interface, electroluminescent devices, and enabling wireless control over electrical appliances. Furthermore, harnessing Faraday's induction law and exploiting human body's intrinsic antenna properties, the TSA-ionogel seamlessly transforms into an autonomous multifunctional epidermal touch panel. This touch panel offers impeccable input capabilities through word inscription and participation in the Chinese game of Go. Consequently, the TSA-ionogel's innovation holds the potential to reshape the trajectory of next-generation electronics and profoundly revolutionize the paradigm of human-machine interaction.

Clinical impact of human parainfluenza virus infections before and during the COVID-19 pandemic in Southern China.

Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory tract infections (ARTIs). Non-pharmaceutical interventions (NPIs) were widely administered to combat the pandemic of the coronavirus disease 2019 (COVID-19). Respiratory specimens were obtained from 10,454 hospitalized children with ARTIs to detect HPIV. We investigated differences in epidemiological and clinical characteristics of HPIV infections before (2017-2019) and during the COVID-19 pandemic (2020-2022). HPIVs were detected in 392 (3.75%, 392/10,454) patients, of whom 70 (17.86%), 48 (12.24%), and 274 (69.90%) were positive for HPIV1, HPIV2, and HPIV3, respectively. Detection rates of HPIV3 were higher in 2020-2022 than in 2017-2019 (3.38% vs. 2.24%). The seasonal distribution of HPIV1 showed no difference, but HPIV3 peaked between September and December during the COVID-19 pandemic, which differed from previous epidemiological patterns. Compared to the period before the COVID-19 pandemic, there has been a noticeable decrease in the incidence of asthma, moist rales, and emesis in patients infected with HPIV1 and in asthma, expectoration, and severe pneumonia in patients infected with HPIV3 during 2020-2022. The detection rates of HPIV increased in Southern China during the COVID-19 outbreak, which underlines the importance of continuous surveillance of HPIV in the next epidemic season.

Competition between Elimination and Substitution for Ambident Nucleophiles CN- and Iodoethane Reactions in Gaseous and Aqueous Medium.

Nucleophilic substitution (SN2) and elimination (E2) reactions between ambident nucleophiles have long been considered as typical reactions in organic chemistry, and exploring the competition between the two reactions is of great importance in chemical synthesis. As a nucleophile, CN- can use its C and N atoms as the reactive centers to undergo E2 and SN2 reactions, but related research is currently limited. This study uses the CCSD(T)/pp/t//MP2/ECP/d electronic structure method to perform detailed investigations on the potential energy profiles for SN2 and E2 reactions between CN- and CH3CH2I in gaseous and aqueous media. The potential energy profiles reveal that the energy barriers for SN2 and E2 reactions with the C atom as the reactive center are consistently lower than those with the N atom, indicating that the C atom has a stronger nucleophilic ability and stronger basicity. Furthermore, the potential energy profiles in both gas and aqueous environments show that the barriers of SN2 reactions are lower than those for E2 reactions with both C and N as the attacking atom. By using the frontier molecular orbital and activation strain models to explain the interesting phenomenon, the transition from the gas phase to solution was investigated, specifically in the gas-microsolvation-water transition. The results show that water molecules reduce the nucleophilicity and basicity of CN-, while strain energy (ΔEstrain) causes a greater increase in the energy barrier for E2 reactions. This study provides new insights and perspectives on the understanding of CN- as a nucleophile in SN2 reactions and serves as theoretical guidance for organic synthesis.

Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11.

OBJECTIVES: Systemic sclerosis (SSc) is a rare rheumatic disease characterized by vascular damage, dysregulated immune response, and fibrosis. Interleukin-11 (IL-11) is upregulated in SSc. This study aimed to investigate the pathological and therapeutic role of the IL-11 trans-signaling pathway in SSc. METHODS: Plasma IL-11 level was evaluated in 32 patients with SSc and 15 healthy controls, while the expression levels of ADAM10, ADAM17, IL-11, IL-11 Rα, or IL-11 co-stained with CD3 or CD163 in the skin of SSc patients and healthy controls were analyzed. Fibroblasts were treated with IL-11 and ionomycin to evaluate the profibrotic effect of IL-11 trans-signaling pathway. TJ301 (sgp130Fc) and WP1066 (a JAK2/STAT3 inhibitor) intervention groups were set up to investigate the antifibrotic effect of targeting IL-11. RESULTS: Levels of plasma IL-11 were extremely low in most SSc patients and healthy controls. In contrast, levels of IL-11, IL-11 Rα, and ADAM10, but not ADAM17, were significantly elevated in the skin of SSc patients. Moreover, the numbers of IL-11+ CD3+ cells and IL-11+ CD163+ cells were increased in the skin of SSc patients. Besides, IL-11 and ADAM10 were also elevated in the skin and pulmonary of bleomycin-induced SSc mouse. Fibroblasts co-stimulated with IL-11 and ionomycin showed increased expression of COL3 and phosphorylation of STAT3, which could be inhibited by TJ301 or WP1066. TJ301 also ameliorated skin and lung fibrosis in BLM-induced SSc mouse. CONCLUSIONS: IL-11 induces fibrosis in SSc by regulating the trans-signaling pathway. Blockage of sgp130Fc or inhibition of the JAK2/STAT3 pathway could ameliorate the profibrotic effect of IL-11.

All Resistive Pressure-Temperature Bimodal Sensing E-Skin for Object Classification.

Electronic skin (E-skin) with multimodal sensing ability demonstrates huge prospects in object classification by intelligent robots. However, realizing the object classification capability of E-skin faces severe challenges in multiple types of output signals. Herein, a hierarchical pressure-temperature bimodal sensing E-skin based on all resistive output signals is developed for accurate object classification, which consists of laser-induced graphene/silicone rubber (LIG/SR) pressure sensing layer and NiO temperature sensing layer. The highly conductive LIG is employed as pressure-sensitive material as well as the interdigital electrode. Benefiting from high conductivity of LIG, pressure perception exhibits an excellent sensitivity of -34.15 kPa-1 . Meanwhile, a high temperature coefficient of resistance of -3.84%°C-1 is obtained in the range of 24-40 °C. More importantly, based on only electrical resistance as the output signal, the bimodal sensing E-skin with negligible crosstalk can simultaneously achieve pressure and temperature perception. Furthermore, a smart glove based on this E-skin enables classifying various objects with different shapes, sizes, and surface temperatures, which achieves over 92% accuracy under assistance of deep learning. Consequently, the hierarchical pressure-temperature bimodal sensing E-skin demonstrates potential application in human-machine interfaces, intelligent robots, and smart prosthetics.

[Corrigendum] Role of the EZH2/miR­200 axis in STAT3­mediated OSCC invasion.

Following the publication of the above article, an interested reader drew to the authors' attention that, in Figs. 7A and 8A. apparently the same mouse had been featured to represent two different experimental groups, albeit displaying distinct fluorescence values. Moreover, following an independent investigation in the Editorial Office, an additional instance of probable data duplication was also noted, comparing between the 'SCC15 / si­NC' cell migration image in Fig. 2D and the 'SCC15­EV' migration assay image in Fig. 1C. After having consulted their original data, the authors realized that these errors arose during the process of assembling the images for Figs. 2 and 8. First, the image for the DZNep (42d) experiment in Fig. 7A had inadvertently been used for the mimic NC (7d) experiment in Fig. 8A; moreover, the 'SCC15 / si­NC' cell migration image in Fig. 2D had been selected incorrectly. The revised versions of Figs. 2 and 8, showing the correct data for the the 'SCC15 / si­NC' cell migration image in Fig. 2D and the mimic NC (7d) experiment in Fig. 8A, are shown on the next two pages. The authors regret that these errors went unnoticed prior to publication, and thank the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 52: 1149­1164, 2018; DOI: 10.3892/ijo.2018.4293].

Ultrastretchable High-Conductivity MXene-Based Organohydrogels for Human Health Monitoring and Machine-Learning-Assisted Recognition.

Conductive hydrogels as promising candidates of wearable electronics have attracted considerable interest in health monitoring, multifunctional electronic skins, and human-machine interfaces. However, to simultaneously achieve excellent electrical properties, superior stretchability, and a low detection threshold of conductive hydrogels remains an extreme challenge. Herein, an ultrastretchable high-conductivity MXene-based organohydrogel (M-OH) is developed for human health monitoring and machine-learning-assisted object recognition, which is fabricated based on a Ti3C2Tx MXene/lithium salt (LS)/poly(acrylamide) (PAM)/poly(vinyl alcohol) (PVA) hydrogel through a facile immersion strategy in a glycerol/water binary solvent. The fabricated M-OH demonstrates remarkable stretchability (2000%) and high conductivity (4.5 S/m) due to the strong interaction between MXene and the dual-network PVA/PAM hydrogel matrix and the incorporation between MXene and LS, respectively. Meanwhile, M-OH as a wearable sensor enables human health monitoring with high sensitivity and a low detection limit (12 Pa). Furthermore, based on pressure mapping image recognition technology, an 8 × 8 pixelated M-OH-based sensing array can accurately identify different objects with a high accuracy of 97.54% under the assistance of a deep learning neural network (DNN). This work demonstrates excellent comprehensive performances of the ultrastretchable high-conductive M-OH in health monitoring and object recognition, which would further explore extensive potential application prospects in personal healthcare, human-machine interfaces, and artificial intelligence.

Antibodies against the Ebola virus soluble glycoprotein are associated with long-term vaccine-mediated protection of non-human primates.

The 2013 Ebola epidemic in Central and West Africa heralded the emergence of wide-spread, highly pathogenic viruses. The successful recombinant vector vaccine against Ebola (rVSVΔG-ZEBOV-GP) will limit future outbreaks, but identifying mechanisms of protection is essential to protect the most vulnerable. Vaccine-induced antibodies are key determinants of vaccine efficacy, yet the mechanism by which vaccine-induced antibodies prevent Ebola infection remains elusive. Here, we exploit a break in long-term vaccine efficacy in non-human primates to identify predictors of protection. Using unbiased humoral profiling that captures neutralization and Fc-mediated functions, we find that antibodies specific for soluble glycoprotein (sGP) drive neutrophil-mediated phagocytosis and predict vaccine-mediated protection. Similarly, we show that protective sGP-specific monoclonal antibodies have elevated neutrophil-mediated phagocytic activity compared with non-protective antibodies, highlighting the importance of sGP in vaccine protection and monoclonal antibody therapeutics against Ebola virus.

Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis: A Randomized Clinical Trial.

Importance: Olamkicept, a soluble gp130-Fc-fusion-protein, selectively inhibits interleukin 6 (IL-6) trans-signaling by binding the soluble IL-6 receptor/IL-6 complex. It has anti-inflammatory activities in inflammatory murine models without immune suppression. Objective: To assess the effect of olamkicept as induction therapy in patients with active ulcerative colitis. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled phase 2 trial of olamkicept in 91 adults with active ulcerative colitis (full Mayo score ≥5, rectal bleeding score ≥1, endoscopy score ≥2) and an inadequate response to conventional therapy. The study was conducted at 22 clinical study sites in East Asia. Patients were recruited beginning in February 2018. Final follow-up occurred in December 2020. Interventions: Eligible patients were randomized 1:1:1 to receive a biweekly intravenous infusion of olamkicept 600 mg (n = 30) or 300 mg (n = 31) or placebo (n = 30) for 12 weeks. Main Outcomes and Measures: The primary end point was clinical response at week 12 (defined as ≥3 and ≥30% decrease from baseline total Mayo score; range, 0-12 [worst] with ≥1 decrease and ≤1 in rectal bleeding [range, 0-3 {worst}]). There were 25 secondary efficacy outcomes, including clinical remission and mucosal healing at week 12. Results: Ninety-one patients (mean age, 41 years; 25 women [27.5%]) were randomized; 79 (86.8%) completed the trial. At week 12, more patients receiving olamkicept 600 mg (17/29 [58.6%]) or 300 mg (13/30 [43.3%]) achieved clinical response than placebo (10/29 [34.5%]), with adjusted difference vs placebo of 26.6% (90% CI, 6.2% to 47.1%; P = .03) for 600 mg and 8.3% (90% CI, -12.6% to 29.1%; P = .52) for 300 mg. Among patients randomized to receive 600 mg olamkicept, 16 of 25 secondary outcomes were statistically significant compared with placebo. Among patients randomized to receive 300 mg, 6 of 25 secondary outcomes were statistically significant compared with placebo. Treatment-related adverse events occurred in 53.3% (16/30) of patients receiving 600 mg olamkicept, 58.1% (18/31) receiving 300 mg olamkicept, and 50% (15/30) receiving placebo. The most common drug-related adverse events were bilirubin presence in the urine, hyperuricemia, and increased aspartate aminotransferase levels, and all were more common in the olamkicept groups compared with placebo. Conclusions and Relevance: Among patients with active ulcerative colitis, biweekly infusion of olamkicept 600 mg, but not 300 mg, resulted in a greater likelihood of clinical response at 12 weeks compared with placebo. Further research is needed for replication and to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifier: NCT03235752.

Ultrasound-Mediated Antitumor Therapy via Targeted Acoustic Release Carrier of Carbon Monoxide (TARC-CO).

As one of the most valuable endogenous gas signaling molecules, carbon monoxide (CO) has been demonstrated in numerous studies to show excellent promise in the treatment of diseases, such as cancer. However, for many years, the inherent high affinity of CO for hemoglobin severely impeded the clinical transformation of CO-based treatments. Therefore, the controlled delivery of CO to target tissues has become a common challenge. Herein, an efficient ultrasonic-triggered and targeted CO release strategy was constructed based on a novel targeted acoustic release carrier of carbon monoxide (TARC-CO) that we synthesized in this study. The designed TARC-COs could afford a safe, stable, and ultrasound-guided delivery of CO in vivo by loading a specified dose of CO inside microbubbles, resulting in breast tumor suppression. Taking advantage of the high loading capacity of microbubbles, the unit volume of TARC-CO suspension could encapsulate up to 337.1 ± 8.0 (×103 ppm) of CO. In addition, the satisfactory ultrasound contrast-enhanced ability of TARC-COs achieved real-time interactive guidance and visual policing of CO delivery. For the in vitro antitumor study, TARC-COs with ultrasonic irradiation were demonstrated to effectively induce mitochondrial dysfunction by reducing mitochondrial membrane potential, leading to the apoptosis of 4T1 cells. In addition, we realized that TARC-CO-based treatment could significantly slow the growth rate of tumors by inducing apoptosis, inhibiting the proliferation of cancer cells, and limiting tumor angiogenesis. In summary, this proof-of-concept study demonstrates the feasibility and tremendous potential of TARC-COs for controlled release of CO, which can be expected to provide new inspirations and a promising perspective for therapy based on active gases.

Enhanced Acoustic Droplet Vaporization through the Active Magnetic Accumulation of Drug-Loaded Magnetic Particle-Encapsulated Nanodroplets (MPE-NDs) in Cancer Therapy.

The application of drug-loaded nanodroplets is still limited by their insufficient accumulation owing to the enhanced permeability and retention (EPR) effect failure in cancer therapy. To overcome these limitations, we propose an alternative magnetic particle-encapsulated nanodroplet (MPE-ND) with outstanding biosafety and magnetic targeting by encapsulating fluorinated Fe3O4-SiO2 nanoparticles inside the liquid core of the nanodroplets. Meanwhile, doxorubicin (DOX) can be stably loaded into the shell through both electrostatic and hydrophobic interactions to obtain drug-loaded MPE-NDs. Both in vitro and in vivo experiments have consistently demonstrated that drug-loaded MPE-NDs can significantly increase the local drug concentration and enhance the damage of tumor tissues through acoustic droplet vaporization under a static magnetic field (eADV therapy). Histological examination reveals that eADV therapy efficiently suppresses tumor proliferation by inducing apoptosis, destroying supply vessels, and inhibiting neovascularization. Drug-loaded MPE-NDs can be expected to open a new gateway for ultrasound-triggered drug delivery and cancer treatment.

Identification of the collagen family as prognostic biomarkers in papillary thyroid carcinoma.

OBJECTIVE: The aim of this study was to construct a collagen-related prognostic model for thyroid cancer and to investigate prognostic value of collagen family genes for thyroid cancer. METHODS: A LASSO Cox regression model for thyroid cancer was developed based on the expression profiles of collagen-related genes. Kaplan-Meier survival analysis was performed for high and low risk groups. The ROC method was used to assess its predictive performance. Predictive independence was verified by multivariate Cox regression analysis. The relationship between this feature and immune cell infiltration was analyzed by tumor microenvironment. COL18A1 was validated by immunohistochemistry and RT-PCR in thyroid cancer tissues. The effect of COL18A1 on cell proliferation, migration and invasion ability of tumor cells were further valuated by CCK-8 assay and transwell assay. The effect of COL18A1 on the immune escape ability of tumor cells was further valuated by cytotoxicity assays. RESULTS: A model including 4 collagen family genes was developed to predict thyroid cancer prognosis. Patients with high-risk score had a poorer prognosis than those with low-risk scores for 1-, 2-, 3-, and 5- year survival. The model independently predicted prognosis after adjusting for other prognostic factors. A nomogram combining risk score and age was constructed with high sensitivity and specificity. This feature was significantly associated with immune cell infiltration. COL18A1 was aberrantly over-expressed in thyroid cancer compared with control tissues and significantly increased proliferative capacity, migration capacity, invasion capacity, and immune escape ability of tumor cells. CONCLUSION: Our findings establish a signature associated with collagen family genes that can be a promising tool to predict the prognosis of thyroid cancer. High COL18A1 expression significantly correlates with the poor prognosis of patients and enhances the immune escape ability of tumor cells.

Volatile Organic Compounds of Streptomyces sp. TOR3209 Stimulated Tobacco Growth by Up-Regulating the Expression of Genes Related to Plant Growth and Development.

To investigate the mechanism underlying the plant growth-promoting (PGP) effects of strain Streptomyces sp. TOR3209, PGP traits responsible for indoleacetic acid production, siderophore production, and phosphate solubilization were tested by culturing the strain TOR3209 in the corresponding media. The effects of volatile organic compounds (VOCs) produced by the strain TOR3209 on plant growth were observed by co-culturing this strain with tobacco seedlings in I-plates. Meanwhile, the effects of VOCs on tobacco gene expression were estimated by performing a transcriptome analysis, and VOCs were identified by the solid-phase micro-extraction (SPME) method. The results showed positive reactions for the three tested PGP traits in the culture of strain TOR3209, while the tobacco seedlings co-cultured with strain TOR3209 revealed an increase in the fresh weight by up to 100% when compared to that of the control plants, demonstrating that the production VOCs was also a PGP trait. In transcriptome analysis, plants co-cultured with strain TOR3209 presented the highest up-regulated expression of the genes involved in plant growth and development processes, implying that the bacterial VOCs played a role as a regulator of plant gene expression. Among the VOCs produced by the strain TOR3209, two antifungal molecules, 2,4-bis(1,1-dimethylethyl)-phenol and hexanedioic acid dibutyl ester, were found as the main compounds. Conclusively, up-regulation in the expression of growth- and development-related genes via VOCs production is an important PGP mechanism in strain TOR3209. Further efforts to explore the effective VOCs and investigate the effects of the two main VOCs in the future are recommended.

Serum-derived extracellular vesicles mediate Smad4 expression through shuttling microRNA-27a in the progression of laryngeal squamous cell carcinoma.

Serum-derived extracellular vesicles (EVs) containing non-coding RNAs have been indicated to serve as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma (LSCC), while their functional role remains to be explored. Here, we summarize the possible mechanism explaining the laryngeal carcinogenesis and the associated changes with the involvement of extracellular microRNA (miR)-27a from serum of LSCC patients. Serum-derived EVs from LSCC patients were found to increase the proliferative activity and decreased the apoptotic activity of LSCC cells. miRNA microarrays revealed that miR-27a expression was elevated after EV treatment. miR-27a expression was elevated in LSCC tissues and predicted a poor prognosis for patients. Downregulation of miR-27a inhibited the effect of EVs to reduce the activity of LSCC cells in vitro and to suppress tumor development in vivo. miR-27a targeted SMAD family member 4 (Smad4) to mediate the Wnt/ß-catenin pathway, which was induced under the influence of EVs. Smad4 was downregulated in LSCC tissues, and simultaneous overexpression of miR-27a and Smad4 resulted in reduced cell activity and tumorigenicity. In conclusion, serum-derived EVs support the laryngeal carcinogenesis at least partially via transferring miR-27a. miR-27a targets Smad4 and is a biomarker to predict LSCC prognosis.

Circ-RHOJ.1 regulated myocardial cell proliferation and apoptosis via targeting the miR-124-3p/NRG-1 axis in myocardial ischemia/reperfusion injury.

Introduction: Myocardial ischemia/reperfusion (I/R) injury is a leading cause of cardiac dysfunction. Circular RNAs (circRNAs) are involved in the pathogenesis of myocardial I/R injury. However, the functions and underlying mechanisms are unclear. The present study determined the role of circ-RHOJ.1 in regulating myocardial cell proliferation and apoptosis after I/R injury. Material and methods: Myocardial cells isolated from Sprague-Dawley rats were identified with an immunofluorescence assay using cardiac troponin T antibody. Expression of circ-RHOJ.1, miR-124-3p and neuregulin-1 (NRG1) mRNA was assessed with real-time quantitative polymerase chain reaction. NRG1 protein expression was evaluated with western blot and immunofluorescence assays. Dual-luciferase reporter assay was performed to confirm interaction between miR-124-3p and circ-RHOJ.1, and miR-124-3p and NRG1. Effects of circ-RHOJ.1 overexpression or miR-124-3p inhibition on cell proliferation and apoptosis were evaluated using cell counting kit (CCK)-8 assay and flow cytometry. Cytokines levels were analyzed with an enzyme-linked immunosorbent assay. Results: Myocardial cells were successfully isolated and had down-regulated expression of circ-RHOJ.1 and NRG1, and up-regulated expression of miR-124-3p after I/R injury. circ-RHOJ.1 acted as a sponge for miR-124-3p, and NRG1 served as a target gene of miR-124-3p. circ-RHOJ.1 overexpression or miR-124-3p inhibition increased interleukin (IL)-10 levels and reduced IL-2, IL-6, and tumor necrosis factor-α levels in myocardial cells after I/R injury. Functional assay results illustrated that circ-RHOJ.1 overexpression or miR-124-3p inhibition enhanced proliferation and inhibited apoptosis of myocardial cells after I/R injury. Conclusions: Circ-RHOJ.1 served as a molecular marker of myocardial I/R injury via regulation of miR-124-3p and NRG1 expression.

Pressure-Induced Superconductivity in HgTe Single-Crystal Film.

HgTe film is widely used for quantum Hall well studies and devices, as it has unique properties, like band gap inversion, carrier-type switch, and topological evolution depending on the film thickness modulation near the so-called critical thickness (63.5 Å), while its counterpart bulk materials do not hold these nontrivial properties at ambient pressure. Here, much richer transport properties emerging in bulk HgTe crystal through pressure-tuning are reported. Not only the above-mentioned abnormal properties can be realized in a 400 nm thick bulk HgTe single crystal, but superconductivity is also discovered in a series of high-pressure phases. Combining crystal structure, electrical transport, and Hall coefficient measurements, a p-n carrier type switching is observed in the first high-pressure cinnabar phase. Superconductivity emerges after the semiconductor-to-metal transition at 3.9 GPa and persists up to 54 GPa, crossing four high-pressure phases with an increased upper critical field. Density functional theory calculations confirm that a surface-dominated topologic band structure contributes these exotic properties under high pressure. This discovery presents broad and efficient tuning effects by pressure on the lattice structure and electronic modulations compared to the thickness-dependent critical properties in 2D and 3D topologic insulators and semimetals.

Arterial Labeling Ultrasound Subtraction Angiography (ALUSA) Based on Acoustic Phase-Change Nanodroplets.

Biomedical imaging technology (like digital subtraction angiography (DSA)) based on contrast agents has been widely employed in the diagnosis of vascular-related diseases. While the DSA achieves the high-resolution observation of specified vessels and their downstream perfusion at the cost of invasive, radioactive operation and hepatorenal toxicity. To address those problems, this study develops arterial labeling ultrasound (US) subtraction angiography (ALUSA) based on a new perfluorobutane (PFB) nanodroplets with a lower vaporization threshold through spontaneous nucleation. The nanodroplets can be selectively vaporized to microbubbles, indicating a highly echogenic signal at B-mode images only using a diagnostic transducer. By labeling a single blood vessel for nanodroplets vaporization and tracking its downstream blood perfusion in segmental renal arteries at a frame rate of 500 Hz. The results demonstrate the color-coded super-resolution ALUSA image, exhibiting the downstream arcuate and interlobular arteries of each segmental renal artery with a resolution of 36 µm in a rabbit kidney. Furthermore, ALUSA could offer the vascular structures, blood flow velocity, and direction of their primary supply vessels in the mouse breast tumor. ALUSA fills the gap of noninvasive labeling angiography in US and opens a broad vista in the diagnosis and treatment of tumor and vascular-related diseases.

Investigation into the role of Stmn2 in vascular smooth muscle phenotype transformation during vascular injury via RNA sequencing and experimental validation.

This study examined the effects of Stmn2 on phenotype transformation of vascular smooth muscle in vascular injury via RNA sequencing and experimental validation. Total RNA was extracted for RNA sequencing after 1, 3 and 5 days of injury to screen the differentially expressed genes (DEGs). Western blot was used to detect the protein expression of Stmn2 and its associated targets. The morphological changes of carotid arteries in rats were examined by hematoxylin and eosin (H&E) staining. The expression of vascular smooth muscle cell (VSMC) phenotype markers smooth muscle alpha-actin (α-SMA), vimentin and OPN were detected by immunohistochemistry. DEGs were related to the extracellular matrix and other cell components outside the plasma membrane. They were associated with protein binding, cytoskeleton protein binding, signal receptor binding and other molecular functions, actin cytoskeleton regulation and other Kyoto Encyclopedia of Genes and Genomes pathways. Stmn2 was identified as the hub gene of actin cytoskeleton pathway and vascular disease, and its expression followed the trend of decreasing initially and increasing afterwards during the progress of vascular injury. Western blot assay showed that the expression of Stmn2 and Tubulin decreased immediately after vascular injury; Stmn2 overexpression significantly up-regulated the expression of osteopontin and α-SMA and vimentin in VSMCs. The results of morphology analysis and immunostaining also showed that Stmn2 overexpression promoted the intima thickening and enhanced the proliferating cell nuclear antigen expression in the injured vascular tissues. In conclusion, our results implied that Stmn2 may play a potential role in vascular injury, which may be associated with VSMC phenotype transformation. Further studies are warranted to determine detailed molecular mechanisms of Stmn2 in vascular injury.