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Abstract Mortise and tenon joint is a key connecting component in timber-framed architecture. Accurately assessing the damage to joints is crucial for the structural design of wooden buildings. This study conducted fatigue tests at three stress levels (70%, 100%, and 130%) based on the maximum stress from static bending tests to analyze the impact of different stress levels on the fatigue performance of mortise and tenon joints. The results showed that the deformation increased as the stress level increased. The energy loss per cycle de-creased and then increased at 130% stress level, and remained essentially constant at 70% and 100% levels. Then, micro-CT scanning was performed on the specimens after fatigue testing. The ambient occlusion algorithm was used to identify the outer boundaries of the tenon, which can distinguish internal cracks from outside air. The sphericity index was used to differentiate between pores and cracks. Three-dimensional visualization analysis was performed on the specimens, and the obtained information on pores and cracks was quantitatively analyzed. The results indicated that deformation and fracture of the tenon were the primary causes of joint damage. The layer-by-layer porosity of the undeformed portion of the tenon remained essentially constant and was lower than that of the fractured region and higher than that of the deformed region. This study analyzed the damage behavior of mortise and tenon joints under different stress levels, contributing to the design and protection of wooden structure buildings.

While the industry has produced sugar-derived ethanol from the conventional method of fermentation for hundreds of years, other effective routes involving the direct transformation of carbohydrates still remain extremely rare. Very recently, an innovative chemo-catalytic method driven by the aqueous-phase catalysis was created for the synthesis of cellulosic ethanol, making a great breakthrough in the common ways as it can theoretically utilize all of the carbon atoms in sugars with faster kinetics; up to now, results from the relevant studies have been accumulated to a certain extent, but the periodic conclusions in this field are unfortunately absent. For this reason, this work tries to offer an overview of the cellulosic ethanol produced by chemo-catalytic routes, highlighting the present knowledge in relation to the technical efficiency, catalytic mechanisms as well as practical applications. At first, the advanced progress on the increasing efficiency from a varied type of catalytic systems are extensively discussed, which involves the specific functions of hybrid components from different strategies; meanwhile, the general influences of processing conditions, such as the hydrothermal severity and aqueous environments, are also identified. Subsequently, possible mechanisms behind the chemo-catalytic processes are widely elaborated by analyzing a number of experimental cases associated with the reaction network and its kinetic models. After that, the actual effects of this technique on the real biomass are collected to identify the positive/negative interactions between multiple components, together with the potential solutions on the semi-continuous processes of pilot scale application. The techno-economic analysis (TEA) is also calculated and compared with other similar methods, such as fermentation and gasification. Finally, several proposals aimed at upgrading the whole chain of chemo-catalytic processes are clearly provided, which may function as a guideline for future studies on the production of bio-ethanol from lignocellulosic materials.

In order to understand the behavior of gas-solid two-phase flow motion and the process of pulverized coal separation in coal mill separator, the numerical simulations on the gas-solid two-phase flow in the separator of a laboratory-scale coal mill were carried out. In the framework of the Eulerian-Lagrangian method, the realizable k-ɛ turbulence model was used to describe the gas-phase field and the discrete phase model with the random walk model was used to describe the pulverized coal particle motion in the simulations. On the basis of cell independence verification, the results of one-way coupling and two-way coupling simulations were compared with the experiments. It is found that the particle size distribution of pulverized coal obtained by the two-way coupling method agrees better with the experimental data than that obtained by the one-way coupling method. The gas phase flow behavior, particle motion characteristics and separator performance in the laboratory-scale coal mill separator were further investigated using a two-way coupling method. The results show that the particle overflow occurs later and the overflow lasts longer when using the two-way coupling method. Because of the effect of particles, the airflow velocity difference between the inner wall of the separator and the outer wall of the inner cone of the separator becomes large, and the uniformity of airflow velocity distribution in the inner cone becomes poor, and there are obvious backflow regions in the primary and secondary separation zones. With the increase of the inlet airflow velocity, the particle overflow rate increases, and the particle discharge rate decreases linearly. The inlet airflow velocity has a small influence on the total particle return rate but has a profound influence on the grade return rate. The grade return rate exhibits a unimodal distribution at the lower airflow velocity, and it displays a bimodal distribution at the higher airflow velocity. When the inlet airflow velocity remains constant, the grade separation efficiency increases as the particle diameter increases. The greater the inlet airflow velocity, the slower the grade separation efficiency increases with the particle diameter, and the larger the cut-off diameter of the separator.

Rice blast, a prevalent and highly destructive rice disease that significantly impacts rice yield, is caused by the rice blast fungus. In the present study, a strain named MTC-8, identified as Bacillus mojavensis, was demonstrated has strong antagonistic activity against the rice blast fungus, Rhizoctonia solani, Ustilaginoidea virens, and Bipolaria maydis. The potential biocontrol agents were identified using ultra-performance liquid chromatography—tandem mass spectrometry (UPLC-MS/MS) analysis and chromatography. Further investigations elucidated the inhibitory mechanism of the isolated compound and demonstrated its ability to suppress spore germination, alter hyphal morphology, disrupt cell membrane integrity, and induce defense-related gene expression in rice. MTC-8 promoted plant growth and may lead to the development of a biocontrol agent that meets agricultural standards. Overall, the Bacillus mojavensis MTC-8 strain exerted beneficial effects on plant growth, immunity and disease resistance against rice blast fungus. In this study, we isolated and purified a bioactive substance from fermentation broth, and the results provide a foundation for the development and application of biopesticides. Elucidation of the inhibitory mechanism against rice blast fungus provides theoretical support for the identification of molecular targets. The successful development of a biocontrol agent lays the groundwork for its practical application in agriculture.

China's food industry has witnessed rapid and accelerated development in recent years, which poses higher demands on the quality of food talents. Drawing on Xi Jinping's Thought on Socialism with Chinese Characteristics for a New Era, this paper argues for the necessity of constructing a multi-dimensional integration cultivation system for first-class food talents. It also points out that universities, as the main carriers of talent cultivation, should explore the methods and approaches of constructing such a system by integrating moral and intellectual education, discipline and specialty, scientific research and teaching, and industry and specialty. To cultivate talents with moral integrity through party building and ideological and political education in curriculum, to foster students' professional growth through the coordinated development of discipline and specialty and the mutual assistance of teaching and scientific research, and to enhance students' diversified development through the optimization of curriculum resource allocation. By doing so, this paper addresses the questions of "what kind of people to cultivate?" and "how to cultivate?", aiming to provide a strong talent resource support for the development of food industry.

The dimensions of tenons in solid wood furniture significantly influence the mechanical performance of mortise and tenon joints. While previous studies have primarily focused on tenon length, width, and thickness, they often overlooked the impact of clearance between the mortise and tenon. This study investigates the effects of tenon length, tenon width, and clearance on the mechanical performance of mortise and tenon joints, aiming to enhance their bending moment capacity (BMC) and stiffness. A three-factor, three-level orthogonal test was conducted, utilizing range analysis and variance analysis to assess the effects of each factor on BMC and stiffness. The LSD post hoc test was employed to identify significant differences between levels of the same factor, and nonlinear regression analysis was used to fit the experimental results. Based on orthogonal experiment outcomes, a grey relational theory-based evaluation system was developed to assess the comprehensive performance of joints, including both moment capacity and stiffness. Results indicate that tenon length has the most significant effect on BMC, followed by clearance and tenon width, while clearance has the greatest impact on stiffness, followed by tenon length and tenon width. These findings are consistent with those obtained from grey relational analysis. When considering both BMC and stiffness as a comprehensive evaluation, the optimal combination is a tenon length of 40 mm, a tenon width of 35 mm, and a clearance of −0.1 mm. This study offers valuable insights for the rational design of mortise and tenon joints, contributing to improved performance and reduced manufacturing costs.

Summary: Dysregulated macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes underlies impaired cutaneous wound healing. This study reveals Vγ4+ γδ T cells spatiotemporally calibrate macrophage trajectories during skin repair via sophisticated interferon-γ (IFN-γ) conditioning across multiple interconnected tissues. Locally within wound beds, infiltrating Vγ4+ γδ T cells directly potentiate M1 activation and suppress M2 polarization thereby prolonging local inflammation. In draining lymph nodes, infiltrated Vγ4+ γδ T cells expand populations of IFN-γ-competent lymphocytes which disseminate systemically and infiltrate into wound tissues, further enforcing M1 macrophages programming. Moreover, Vγ4+γδ T cells flushed into bone marrow stimulate increased IFN-γ production, which elevates the output of pro-inflammatory Ly6C+monocytes. Mobilization of these monocytes continually replenishes the M1 macrophage pool in wounds, preventing phenotypic conversion to M2 activation. Thus, multi-axis coordination of macrophage activation trajectories by trafficking Vγ4+ γδ T cells provides a sophisticated immunological mechanism regulating inflammation timing and resolution during skin repair.

To reduce the slope collapse and soil erosion under the action of rainfall erosion in desertification areas, the self-developed nano silicon-based sand-fixation material (Nano-Silicon/Polymer Composites，NSPC) is proposed to protect the sandy slope surface of the Yarlung Zangbo River Valley in Xizang. In view of the unclear effect of NSPC sand-fixing material on strengthening sand body, based on infrared spectrum, viscosity test, contact test and simulated sandy slope rainfall erosion test, the mechanism of NSPC sand-fixation material to strengthen the sandy slope is discussed, and the anti-erosion ability of the NSPC sand-fixation material under the rainfall is studied. The results show that the NSPC sand-fixation material and sand particles cross and intertwine with each other through polymerization and cementation to form a 3D network structure, so as to achieve the purpose of strengthening the sandy body. The rheological properties of the NSPC sand-fixation material belongs to Bingham fluid in the first 1 h, and gradually changes to Newton fluid in the later period. The surface tension of the NSPC sand-fixation material is 60.31 mN/m, the contact angle with sandy body is 48.6°, and the adhesion force is 0.040 N/m, therefor it has strong infiltration ability. The reinforcement layer formed on the sandy slope surface has strong blocking effect on rainwater erosion, and the reinforcement layer also has water retention ability. This study provides test support for the application and promotion of the NSPC sand-fixation material in sand fixation and protection projects in desertification areas.

Abstract Amidst progressive advancements in tissue engineering, there has been a significant enhancement in the efficacy of anti-inflammatory hydrogel dressings, addressing a myriad of clinical challenges on wound healing. A frequent complication during the initial stages of deep second-degree burn wound healing is the onset of an inflammatory storm, typically occurring without effective intervention. This event disrupts normal biological healing sequences, leading to undesirable regression. In response, we have customized a tunable, multidimensional anti-inflammatory hydrogel platform based on sulfated alginates (Algs), loaded with Prussian blue (PB) nanozymes. This platform competently eliminates surplus reactive oxygen species (ROS) present in the wound bed. Algs, functioning as a mimic of sulfated glycosaminoglycans (including heparin, heparan sulfate, and chondroitin sulfate) in the extracellular matrices (ECM), demonstrate a high affinity towards inflammatory chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1). This affinity effectively impedes the infiltration of inflammatory cells into the wound. Concurrently, Algs markedly modulate the macrophage phenotype transition from M1 to M2. Ultimately, our potent anti-inflammatory hydrogels, which strategically target inflammatory chemokines, M1 macrophages, and ROS, successfully attenuate dysregulated hyperinflammation in wound sites. Precise immunomodulation administered to deep second-degree burn wounds in mice has demonstrated promotion of neovascular maturation, granulation tissue formation, collagen deposition, and wound closure. Our biomimetic hydrogels, therefore, represent a significant expansion in the repertoire of anti-inflammatory strategies available for clinical practice.

Abstract Suppressing persistent multidrug-resistant (MDR) bacterial infections and excessive inflammation is the key for treating chronic wounds. Therefore, developing a microenvironment-responsive material with good biodegradability, drug-loading, anti-infection, and anti-inflammatory properties is desired to boost the chronic wounds healing process; however, using ordinary assembly remains a defect. Herein, we propose a pH/enzyme dual-responsive polymyxin B (PMB) spatiotemporal-release hydrogel (GelMA/OSSA/PMB), namely, the amount of OSSA and PMB released from GelMA/OSSA/PMB was closely related the wound pH and the enzyme concentration changing. The GelMA/OSSA/PMB showed better biosafety than equivalent free PMB, owing to the controlled release of PMB, which helped kill planktonic bacteria and inhibit biofilm activity in vitro. In addition, the GelMA/OSSA/PMB exhibited excellent antibacterial and anti-inflammatory properties. A MDR Pseudomonas aeruginosa caused infection was effectively resolved by the GelMA/OSSA/PMB hydrogel in vivo, thereby significantly boosting wound closure during the inflammatory phase. Furthermore, GelMA/OSSA/PMB accelerated the sequential phases of wound repair.

Background: Citrus yellow vein-clearing virus (CYVCV) is a Mandarivirus that causes great economic losses in lemon production. CYVCV infection is associated with obvious yellow vein-clearing disease symptoms and is directly regulated by plant hormone responses. Methods: To understand how lemon plants respond to CYVCV infection, we performed transcriptomic and phytohormone metabolomics. Results: A total of 936 differentially expressed genes were identified, and 773 were downregulated. Salicylic acid and auxin levels increased after CYVCV infection, and phytohormone regulatory systems were also explored. Jasmonic acid and auxin levels decreased after the CYVCV challenge, and jasmonic acid and auxin signaling pathway components were mostly downregulated. The differentially expressed genes (DEGs) involved in the immune response to viral infection, including those related to cell wall integrity, lectin, microtubules, and mildew resistance locus O (MLO), may also provide new candidate targets for CYVCV control. Conclusions: Our findings provide new insights into the molecular changes underlying the pathogenesis of CYVCV in lemon plants.

Abstract Background Efficient re-epithelialization is important for successful skin wound healing. The proportion of epidermal stem cells (EpSCs) and dendritic epidermal T cells (DETCs) determines the extent of wound re-epithelialization, especially in large areas of skin tissue loss. However, it remains unknown whether and how DETCs regulate the status of EpSCs to impact wound re-epithelialization. Methods To investigate how DETCs regulate EpSCs in skin re-epithelialization, we utilized normal or full-thickness skin deficient wide type (WT) mice and Tcrσ knockout (Tcrσ−/−) mice with DETCs or DETCs-derived exosomes (Exos) treatment. Flow cytometry analysis (FCAS), BrdU labelled experiments, immunofluorescence and immunohistochemical assays were performed to detect the proportion of EpSCs in the epidermis. Wound closure rate and re-epithelialization were assayed by a macroscopical view and hematoxylin–eosin (H&E) staining. EpSCs in vitro were co-cultured with DETCs in a transwell-dependent or -independent manner, or supplement with GW4869 or Exos (5 µg/mL, 15 µg/mL and 45 µg/mL), and the proliferation of EpSCs was detected by means of FCAS and CFSE. Results Our data showed that the proportion of CD49fbriCD71dim cells, K15+ cells and BrdU+ cells in the normal epidermis of Tcrδ−/− mice had no significant difference compared to WT mice. For wounded Tcrδ−/− mice, DETCs treatment increase the proportion of CD49fbriCD71dim cells, K15+ cells and BrdU+ cells in the epidermis around the wound in comparison to PBS treatment. DETCs significantly increased the number of CD49fbriCD7dim cells and K15+ cells through transwell-dependent or -independent manners relative to control group. Furthermore, Exos stimuli remarkedly promote the proliferation of EpSCs compared to control group, while the increasement was suppressed when DETCs were interfered with GW4869. Gross observation and H&E staining showed that Exos significantly accelerated wound closure and increased re-epithelialization length in Tcrδ−/− mice when compared to control mice. Additionally, we found in vivo that Exos observably facilitated the proliferation of CD49fbriCD7dim cells and K15+ cells. Conclusions We revealed that DETCs enhanced the proliferation of EpSCs in the epidermis around the wounds to accelerate re-epithelialization in which Exos played important roles in the remote regulation of EpSCs proliferation. Together, these findings suggest a mechanistic link among DETC-derived exosomes, the proliferation of EpSCs, and wound re-epithelialization in the skin.

Background: Coronavirus Disease 2019 (COVID-19) has risen as a global threat to public health and can cause both respiratory and multisystemic diseases in humans. This study aimed to describe the incidence of abnormal liver function tests (LFTs) in post-COVID-19 pregnant women, and to explore characteristics of pregnant women with abnormal LFTs. Methods: This retrospective cohort study comprised 155 pregnant patients who experienced COVID-19, alongside 76 uninfected pregnant women as a control group. All participants were randomly selected from the Obstetrics outpatient clinic at the Affiliated Maternity and Child Health Care Hospital of Nantong University between December 25 2022 and January 31 2023. Demographic data and laboratory data were collected, and results were statistically analyzed. Results: Of the 155 pregnant women who had experienced COVID-19, 63 (40.6%) showed abnormally raised liver enzymes. In the control group, 9 (11.8%) cases had abnormal LFTs. Differences between the two groups were statistically significant (p < 0.05). Of the 63 post-COVID-19 patients with abnormal LFTs, the median serum level of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) was: 175 U/L (range, 51–352 U/L), 113 U/L (range, 42–329 U/L), and 123 U/L (range, 35–250 U/L). Median total biliary acid (TBA) was 18.1 µmol/L (range, 1.8–33.5 µmol/L). The patients who developed abnormal LFTs did so within 7–14 days after contracting COVID-19, with a median of 10 days. Subsequently, their liver function returned to normal within 4–26 days, with a median of 12 days. The univariate analysis on factors that may affect abnormal LFTs revealed a statistically significant difference in gestational age and body mass index (BMI) (p < 0.001). Logistic regression analysis found that gestational age (odds ratio (OR): 1.095 [1.021–1.174]) and BMI (OR: 1.169 [1.059–1.289]) remained a significant independent risk factors for liver injury (p < 0.05). Conclusions: Pregnant women are at an increased risk of liver injury after contracting COVID-19. Moreover, with the increase of gestational age and BMI, the risk of liver injury increases.

Objective(s)To examine associations between Index of Concentration at the Extremes (ICE) measures for economic and racial segregation and HIV outcomes in the United States (U.S.) and Puerto Rico.MethodsCounty-level HIV testing data from CDC's National HIV Prevention Program Monitoring and Evaluation and census tract-level HIV diagnoses, linkage to HIV medical care, and viral suppression data from the National HIV Surveillance System were used. Three ICE measures of spatial polarization were obtained from the U.S. Census Bureau's American Community Survey: ICEincome (income segregation), ICErace (Black-White racial segregation), and ICEincome+race (Black-White racialized economic segregation). Rate ratios (RRs) for HIV diagnoses and prevalence ratios (PRs) for HIV testing, linkage to care within 1 month of diagnosis, and viral suppression within 6 months of diagnosis were estimated with 95% confidence intervals (CIs) to examine changes across ICE quintiles using the most privileged communities (Quintile 5, Q5) as the reference group.ResultsPRs and RRs showed a higher likelihood of testing and adverse HIV outcomes among persons residing in Q1 (least privileged) communities compared with Q5 (most privileged) across ICE measures. For HIV testing percentages and diagnosis rates, across quintiles, PRs and RRs were consistently greatest for ICErace. For linkage to care and viral suppression, PRs were consistently lower for ICEincome+race.ConclusionsWe found that poor HIV outcomes and disparities were associated with income, racial, and economic segregation as measured by ICE. These ICE measures contribute to poor HIV outcomes and disparities by unfairly concentrating certain groups (i.e., Black persons) in highly segregated and deprived communities that experience a lack of access to quality, affordable health care. Expanded efforts are needed to address the social/economic barriers that impede access to HIV care among Black persons. Increased partnerships between government agencies and the private sector are needed to change policies that promote and sustain racial and income segregation.

BackgroundThe optic nerve sheath diameter (ONSD)/eyeball transverse diameter (ETD) ratio has been suggested in the evaluation of intracranial pressure (ICP). The aim of this study was to evaluate the predictive value of ONSD and ONSD/ETD in relation to risk for secondary malignant middle cerebral artery infarction (MMI).MethodsA total of 91 patients with MCA occlusion were included in this study. Data were divided into two groups based on development of MMI or not. ONSD and ETD were measured by unenhanced computed tomography (CT). The differences in ONSD and the ONSD/ETD ratios between the MMI and non-MMI groups were compared. Receiver operating characteristic curve analyses were used to test the diagnostic value of ONSD and ONSD/ETD independently, to predict MMI.ResultsThe ONSD in the MMI group and non-MMI group were 5.744 ± 0.140 mm and 5.443 ± 0.315 mm, respectively (P = 0.001). In addition, the ONSD/ETD ratios in the MMI group and non-MMI group were 0.258 ± 0.008 and 0.245 ± 0.006, respectively (P = 0.001). The receiver operating characteristic (ROC) curve demonstrated an area under the curve (AUC) for ONSD of 0.812 [95% confidence interval (CI): 0.718–0.906, P = 0.001], with a sensitivity of 97.4% and a specificity of 66.0% at the cut-off value of 5.520 mm. The AUC for ONSD/ETD ratio in predicting occurrence of MMI was 0.895 (95% CI: 0.823–0.968, P = 0.001), with a sensitivity of 84.2% and a specificity of 92.5% at a cut-off value of 0.250.ConclusionIn acute stroke patients with massive cerebral infarction, an increased ONSD or ONSD/ETD ratio increases the odds of malignant progression and may be used as an indicator for emergent therapeutic interventions. In addition, the ONSD/ETD ratio may be more valuable than ONSD in predicting the malignant progression of acute stroke patients.

Tumor necrosis factor alpha (TNF-α) is a crucial factor in the control of Mycobacterium tuberculosis (Mtb) infection. Pathogenic mycobacteria can inhibit and/or regulate host cell TNF-α production in a variety of ways to evade antituberculosis (anti-TB) immunity as well as facilitate immune escape. However, the mechanisms by which TNF-α expression in host cells is modulated to the benefit of mycobacteria is still an interesting topic and needs further study. Here, we report that macrophages infected with Mycobacterium marinum (Mm)—a close relative of Mtb—upregulated the expression of E3 ubiquitin ligase FBXW7. Specific silencing FBXW7 with small interfering RNA (siRNA) significantly elevates TNF-α expression and eventually promotes the elimination of intracellular bacteria. In turn, overexpression of FBXW7 in Raw264.7 macrophages markedly decreased TNF-α production. Furthermore, partial inhibition of FBXW7 in an Mm-infected murine model significantly reduced TNF-α tissue content, alleviated tissue damage as well as reduced the bacterial load of mouse tails. Finally, FBXW7 could decrease TNF-α in a K63-linked ubiquitin signaling dependent manner. Taken together, our study uncovered a previously unknown role of FBXW7 in regulating TNF-α dynamics during mycobacterial infection, which provides new insights into understanding the role of FBXW7 in anti-tuberculosis immunity and its related clinical significance.

Abstract Background Restenosis is a serious problem in patients who have undergone percutaneous transluminal angioplasty. Endothelial injury resulting from surgery can lead to endothelial dysfunction and neointimal formation by inducing aberrant proliferation and migration of vascular smooth muscle cells. Exosomes secreted by mesenchymal stem cells have been a hot topic in cardioprotective research. However, to date, exosomes derived from mesenchymal stem cells (MSC-Exo) have rarely been reported in association with restenosis after artery injury. The aim of this study was to investigate whether MSC-Exo inhibit neointimal hyperplasia in a rat model of carotid artery balloon-induced injury and, if so, to explore the underlying mechanisms. Methods Characterization of MSC-Exo immunophenotypes was performed by electron microscopy, nanoparticle tracking analysis and western blot assays. To investigate whether MSC-Exo inhibited neointimal hyperplasia, rats were intravenously injected with normal saline or MSC-Exo after carotid artery balloon-induced injury. Haematoxylin-eosin staining was performed to examine the intimal and media areas. Evans blue dye staining was performed to examine re-endothelialization. Moreover, immunohistochemistry and immunofluorescence were performed to examine the expression of CD31, vWF and α-SMA. To further investigate the involvement of MSC-Exo-induced re-endothelialization, the underlying mechanisms were studied by cell counting kit-8, cell scratch, immunofluorescence and western blot assays. Results Our data showed that MSC-Exo were ingested by endothelial cells and that systemic injection of MSC-Exo suppressed neointimal hyperplasia after artery injury. The Evans blue staining results showed that MSC-Exo could accelerate re-endothelialization compared to the saline group. The immunofluorescence and immunohistochemistry results showed that MSC-Exo upregulated the expression of CD31 and vWF but downregulated the expression of α-SMA. Furthermore, MSC-Exo mechanistically facilitated proliferation and migration by activating the Erk1/2 signalling pathway. The western blot results showed that MSC-Exo upregulated the expression of PCNA, Cyclin D1, Vimentin, MMP2 and MMP9 compared to that in the control group. Interestingly, an Erk1/2 inhibitor reversed the expression of the above proteins. Conclusion Our data suggest that MSC-Exo can inhibit neointimal hyperplasia after carotid artery injury by accelerating re-endothelialization, which is accompanied by activation of the Erk1/2 signalling pathway. Importantly, our study provides a novel cell-free approach for the treatment of restenosis diseases after intervention.

The large volume and weak environmental adaptability of fiber optical frequency combs (OFCs) have become the main obstacles for their applications in various fields. To address these issues, in this study, we present a compact, low-cost f-to-2f interferometer and fiber actuator with a large tuning range and a high control bandwidth for a 200-MHz OFC that is based on a 1.5-μm all-polarization-maintaining fiber mode-locked laser. By employing customized fiber-coupled gradient index lenses, our f-to-2f interferometer is encapsulated in a miniature tube with a diameter of only 4 mm and a length of 40 mm, which substantially reduces the optical section size of the frequency comb as compared to conventional devices. The carrier envelope offset beat with a signal-to-noise ratio of 40 dB is detected in a resolution bandwidth of 360 kHz. In addition, a laboratory-made piezoelectric transducer-driven mechanical actuator for repetition rate regulation exhibited a large tuning range of 106 kHz (corresponding to an effective temperature drift of 53 °C) and a high control bandwidth of approximately 1 kHz. This resulted in a robust repetition rate locking with an Allan deviation of 330 μHz at a gate time of 1 s and a residual integrated timing jitter of 418 fs [3 Hz to 1 MHz] when referenced to a hydrogen maser. Along with reducing the size and improving the environmental adaptability of the OFC, our design can also decrease the power consumption of the system significantly. Our findings provide a new direction to the development of OFCs for various applications.

AimThis study aims to retrospectively evaluate the association between pericarotid inflammation and the presence of embolic stroke of undetermined source (ESUS).MethodsIn total, 126 patients with ESUS and 118 patients with ischemic stroke from large artery atherosclerosis (LAA) were enrolled. All the patients underwent brain MRI and a neck CT angiography (CTA) examination. Reviewers were blinded to infarct location and stroke cause. Paired t-tests assessed within-subjects differences in mean Hounsfield units (HUs) in carotid perivascular fat between the cerebral infarction side and contralateral side for ESUS and LAA ischemic stroke cases. The unpaired Student's t-test was used to assess between-subjects differences in mean HUs between ESUS and LAA ischemic stroke cases.ResultsIn both the ESUS cases and LAA ischemic stroke cases, the pericarotid fat density around the carotid artery ipsilateral to the stroke significantly increased compared with contralateral stroke position in both the groups (ESUS cases −56.31 ± 18.70 vs. −67.31 ± 20.01, p = 0.000; LAA ischemic stroke cases −51.62 ± 19.95 vs. −64.58 ± 22.68, p = 0.000). However, there was no significant difference in ipsilateral and contralateral positions to infarct between ESUS cases and LAA ischemic stroke cases (ipsilateral to infarct −56.31 ± 18.70 vs. −51.62 ± 19.95, p = 0.059; contralateral to infarct −67.31 ± 20.01 vs. −64.58 ± 22.68, p = 0.320).ConclusionWe found increased density in the fat surrounding carotid artery ipsilateral to stroke compared with contralateral in ESUS, suggesting the presence of an inflammatory reaction that extends beyond the vessel lumen in patients with ESUS with a risk factor profile similar to LAA strokes.

Abstract Objectives To investigate the association of eight variants of four matrix metalloproteinase (MMP) genes with ischemic stroke (IS) and whether interactions among these single nucleotide polymorphisms (SNPs) increases the risk of IS. Methods Among 547 patients with ischemic stroke and 350 controls, matrix‐assisted laser desorption/ionization time of flight mass spectrometry was used to examine eight variants arising from four different genes, including MMP‐1 (rs1799750), MMP‐2 (rs243865, rs2285053, rs2241145), MMP‐9 (rs17576), and MMP‐12 (rs660599, rs2276109, and rs652438). Gene–gene interactions were employed using generalized multifactor dimensionality reduction (GMDR) methods. Results The frequency of rs17576 was significantly higher in IS patients than in controls (p = .033). Logistic regression analysis revealed the AG and GG genotypes of rs17576 to be associated with a higher risk for IS, with the odds ratio and 95% confidence interval being 2.490 (1.251–4.959) and 2.494 (1.274–4.886), respectively. GMDR analysis showed a significant SNP‐SNP interaction between rs17576 and rs660599 (the testing balanced accuracy was 53.70% and cross‐validation consistency was 8/10, p = .0107). Logistic regression analysis showed the interaction between rs17576 and rs660599 to be an independent risk factor for IS with an odds ratio of 1.568 and a 95% confidence interval of 1.152–2.135. Conclusion An MMP‐9 rs17576 polymorphism is associated with increased IS risk in the Han Hakka population and interaction between MMP‐9 rs17576 and MMP‐12 rs660599 is associated with increased IS risk as well.

As a potential clinical therapeutic cell for injured tissue repair, mesenchymal stem cells (MSCs) have attracted increasing attention. Enhancing the pro-healing function of MSCs has gradually become an essential topic in improving the clinical efficacy of MSCs. Recently, studies have shown that neuronal protein 3.1 (P311) plays a crucial role in promoting skin wound healing, suggesting P311 gene modification may improve the pro-healing function of MSCs. In this study, we demonstrated that increasing the in vivo expression of P311 could significantly enhance the ability of MSCs to lessen the number of inflammatory cells, increase the expression of IL10, reduce the levels of TNF-α and IFN-γ, increase collagen deposition, promote angiogenesis, and ultimately accelerate skin wound closure and improve the quality of wound healing. Importantly, we uncovered that P311 enhanced the pro-angiogenesis function of MSCs by increasing the production of vascular endothelial growth factor (VEGF) in vitro and in vivo. Mechanistically, we revealed that the mTOR signalling pathway was closely related to the regulation of P311 on VEGF production in MSCs. Together, our data displayed that P311 gene modification in MSCs augments their capabilities to promote skin wound closure, which might bring the dawn for its clinical application in the future.

Objectives. To investigate whether hUC-MSCs attenuated severe burn-induced ALI and the effects were based on TSG-6 secreted from hUC-MSCs. Method. A rat model was established and evaluated as follows: cytokine expression was measured by ELISA, and both inflammatory cell infiltration and lung injury were assessed by immunohistochemistry assay. Results. In vitro, TSG-6 levels in serum from the burn group were significantly increased compared with those from the sham group. In vivo, TSG-6 levels of lung tissues and serum in the burn+hUC-MSC group were significantly increased compared with those in the burn group. Both in lung tissues and in serum, increased levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) were remarkably decreased, but the anti-inflammatory cytokine IL-10 increased after hUC-MSC administration (p

Traditional hydrogel has usually had restricted application in the biomedical field due to lack of a control unit. Herein, Azobenzene (AZO), as a typical kind of photo-response molecule, was introduced into hydrogel by polymerization to provide a control unit for hydrogel. Simultaneously, the immobilization of AZO end group would solve the problems of uncontrollable recovery and light fatigue for AZO small molecules according to previous research. In the research, two kinds of crosslinkable AZO molecules, namely AZO crosslinker and AZO monomer, were synthesized as functional monomers or crosslinkers. Further, AZO copolymerized hydrogel and AZO crosslinked hydrogel were obtained. In order to estimate fundamental properties for contact lenses, gelation time and swelling ratio of hydrogels as a function of AZO concentration as well as crosslinking type were investigated. Moreover, synthesized hydrogels exhibited typical porous morphology, but their size and homogeneity were dependent on the type of hydrogel. In order to evaluate photo-responsive performance, detailed photo induced isomerization of both AZO copolymerized hydrogel and crosslinked hydrogel were tracked by UV spectra. The results confirmed the reversible, stable, and controllable photo responsive process. In vitro evaluation was used to investigate drug release behavior using orfloxacin and puerarin as model drugs. It was found that AZO addition as well as hydrogel type would influence puerarin release, but would have little effect on the orfloxacin release behavior in hydrogels. Furthermore, the isomer type in the hydrogel would have some effects on drug release behavior including orfloxacin and puerarin.

Abstract As an inflammatory factor, IL‐25 has been studied in variouscancers, but it is rarely reported in cancer chemotherapy resistance. Major vault protein (MVP), as a gene associated with lung multidrug resistance, is associated with multiple chemotherapy resistances of lung cancer. However, the relationship between IL‐25 and MVP in lung cancer cells has not been studied. In this study, we found that both IL‐25 and MVP were elevated expressed in cisplatin‐resistant lung adenocarcinoma cell line (A549/CDDP). Silencing of IL‐25 resulted in down‐regulation of MVP expression and reduced cisplatin tolerance of A549/CDDP cells. Overexpression of IL‐25 resulted in increase of MVP expression and the cisplatin tolerance in A549 cells. In addition, we found that the extracellular IL‐25 could stimulate the expression of MVP and activate the NF‐κB signaling pathway. Further, animal models also confirmed that IL‐25 reduced the sensitivity of xenografts to chemotherapy. Taken together, we believe that the up‐regulation of IL‐25 induces MVP expression contributing to chemotherapy resistances of lung cancer cells. Our findings suggest that interference the expression of IL‐25 might be potential treatment strategies for the clinical reversing the chemotherapy resistance.

Abstract Organic compounds that contain nitrogen are very important intermediates in pharmaceutical and chemical industry. Hydroamination is the reaction that can form C–N bond with high atom economy. The research progress in metals catalyzed hydroamination of alkenes and alkynes from the perspective of reaction mechanism is categorized and summarized.

We experimentally investigate the noise properties of a homemade 586 MHz mode-locked laser (MLL). The variation of the timing jitter versus the harmonic order is measured, which is consistent with the theoretical analyses. The dominant contributions to the timing jitter are detailedly studied by analyzing the phase noises at different harmonic frequencies. For low-order harmonics, the intensity noise and relative-intensity-noise-coupled (RIN-coupled) jitter mainly contribute to the timing jitter, while for high-order harmonics, the amplified spontaneous emission (ASE) noise makes the dominant contribution. Then we find that a higher output ratio has an obvious improvement on reducing the timing jitter and suppressing the phase noise because of the shorter pulse duration and lower net cavity dispersion caused by the higher output ratio. Finally a comparison of the noise performance between the MLL and a commercial signal generator is made, which shows that the optically generated radio-frequency signal (OGRFS) has a lower phase noise at high offset frequencies, however the higher phase noise at low offset frequencies leads to a higher timing jitter than the commercial SG.

As a kind of important insect pest of cotton crops, aphids cause serious damage in cotton yields and quality worldwide, posing a significant risk to economic losses. Automatic detection of the pest damage level plays an important role in cotton field management. However, it is usually regarded as a classification problem in machine learning, where the disease severity levels are taken as independent categories and the inter-level relationship has not fully been considered. To utilize the inherited relations among different severity levels caused by cotton aphids, a novel approach based on the spectral index reconstruction was proposed in this study. First, six types of initial spectral indices were reconstructed based on healthy samples in the training set. Then, the severity sequences corresponding to the reconstructed initial spectral indices (RISIs) were sorted and compared with the ideal sequence. After attaining sequences most consistent with the ideal one, the ratio between the inter- and intra- levels was calculated to select the sensitive RISI. Moreover, the range of each severity level was established by the thresholds between adjacent grades of the selected sensitive RISI, which was finally used to determine the disease severity level caused by cotton aphids. Results of the cotton aphids showed that the proposed approach achieved a grading performance with OA = 0.944, AA = 0.900, and Kappa coefficient = 0.928. Hence, the proposed approach based on hyperspectral index reconstruction is effective and has potential application in grading the aphid infestation severity of cotton.

Background: Given the limitations of chemotherapy for the treatment of breast cancer (BC) and the wide exploration of Chinese herbal injections (CHIs), this network meta-analysis (NMA) was conducted to analyze the comparative efficacy and safety of nine CHIs combined with CF (Cyclophosphamide and 5-Fluorouracil) chemotherapy regimens in the treatment of BC.Methods: Several electronic databases were searched to identify randomized controlled trials (RCTs) from inception to January 6, 2020. RCTs were screened by pre-established eligibility criteria, and the quality of which was assessed using the Cochrane risk of bias tool. Outcomes such as the clinical effectiveness rate, performance status, peripheral hemogram, and detection of T-lymphocyte subsets were analyzed using the Winbugs 1.4.3 and Stata 13.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Cluster analysis was performed to compare the effect of CHIs between two or three different outcomes.Results: A total of 84 RCTs involving 7855 patients and nine CHIs were included. The results showed that compared to CF chemotherapy regimens alone, the ones injected along with Aidi, Shenmai, Shenqi Fuzheng, Kangai, Kanglaite, or Shengmai combined with CF can improve the clinical effectiveness rate. Aidi, Shenmai, Shenqi Fuzheng, Compound Kushen, Kangai, and Kanglaite injection combined with CF can improve the performance status. Shenqi Fuzheng injection was considered as a favorable choice for relieving adverse reactions. According to the results of cluster analysis, Aidi injection and Compound Kushen injection plus CF were more favorable for the clinical effectiveness rate and performance status.Conclusion: In conclusion, Shenqi Fuzheng, Compound Kushen, Aidi, and Kangai injection combined with CF chemotherapy regimen have more significant effects for patients with BC. However, more high-quality clinical RCTs, especialy which correctly use blinding and allocation concealment, are required to support the conclusions.

Biochar plays an essential role in soil remediation, but its effect on the arsenic remediation has been controversial. In this study, hexadecyl trimethyl ammonium bromide (HDTMA-Br) modified or unmodified biochar on As mobility and bioavailability in soil were studied. The sequential extraction experiment showed that As in the original soil mainly existed in the occluded form (78.24%), followed by Fe‒As (20.72%) and Al‒As (0.88%) forms. With the addition of the modified and unmodified biochars, the contents of Ca‒As and Fe‒As increased by 0.36 – 0.95% and 2.06 – 3.36%, respectively, suggesting the increased potential toxicity of As. The NaH2PO4 extraction result showed that the unmodified biochar increased the As availability by 3.23 – 22.76%, whereas the HDTMA-modified biochar reduced the As availability by 4.80 – 13.41%. Pot experiment showed that the unmodified and modified biochar increased the biomass of Brassica pekinensis, and the modified biochar (HB5) decreased the uptake of As by plants by 80.77% compared to the unmodified biochar. In particular, the plant achieved better growth in the modified biochar treatment (average height 8.31 cm) than in the unmodified biochar treatment (average height 6.97 cm). Therefore, both biochars facilitated phase transformation of As from the stable to the mobile states in the soil. Nevertheless, the HDTMA-modified biochar had an effect on alleviating As bioavailability and toxicity.

Synthesized polypeptide is attracting an increased interests due to its excellent biological characteristic and adjustable chemical properties in bio-related fields. But polypeptide itself has no switching properties, which is harmful to the development of its application as a control component. Herein, light-responsive poly(γ-benzyl-L-glutamate)s (PBLGs) is synthesized by a one-step NCA method using p-aminoazobenzene (m-AZO) and p-diaminoazobenzene (m-DAZO) as initiators. PBLGs exhibit amorphous characteristics with obvious Tg transition, which are 14°C for PBLG1 and 21°C for PBLG2. In order to forecast the structure-property information of PBLGs, theoretical UV-vis spectra as well as the energy gap between HOMO and LUMO is calculated by DFT calculation. Experimental results of UV-vis spectra exhibit similar characteristics to those of theorical UV-vis spectra except for the 40–50 nm red-shifting of absorbance peak. Furthermore, the absorbance intensities of PBLGs have a good linear relationship with their concentration, but their linearity range depending on concentration is completely different. Then, trans–cis transition under a different excitation source and cis–trans recovery in a dark environment are tracked in real-time by UV-vis spectra to evaluate the light response performances. It is found that UV light is the only effective excitation source for PBLG1, and blue light is another effective excitation source for PBLG2 besides UV light. Furthermore, the addition of alcohol and water as cosolvents has little effect on trans→cis transition in UV-light-excited systems, but it shortens recovery time of the cis→trans process in a dark environment. By contrast, the detectable isomerization process becomes unclear with the addition of alcohol in blue-light-excited system. Furthermore, either alcohol or water in solvents accelerate both the trans→cis and cis→trans process in a blue-light-excited system.

Objective: Nicorandil exerts a protective effect against coronary microvascular dysfunction in acute myocardial infarction (AMI) patients. However, the mechanism and effect of nicorandil in hyperhomocysteinemia (HHcy) AMI patients remain unclear. Methods: C57/BL6 mice with mild to moderate HHcy and human coronary artery endothelial cells (HCAECs) cotreated with HHcy (1 mmol/L) for 24 h and hypoxia for 6 h were selected as models. Small animal ultrasound detection was used to compare cardiac function. CD31 immunofluorescence staining and tomato lectin staining were used to assess the number of microcirculation changes in vivo. MTT, tube formation and western blotting assays were used to evaluate the effect of nicorandil on HCAECs and the PI3K/Akt/eNOS pathway. Results: The results showed that nicorandil improved cell viability and p-PI3K/PI3K, p-Akt/Akt, and p-eNOS/eNOS expression in the vitro HHcy and hypoxia models. The beneficial effects of nicorandil on HCAECs could be inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the nitric oxide synthase (NOS) inhibitor L-NAME. In vivo, nicorandil improved the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the post-HHcy + MI model, and the levels of CD31 and tomato lectin expression were higher in the nicorandil treatment group. The effectiveness of nicorandil was inhibited in the PI3K and L-NAME groups. Conclusion: The results suggest that nicorandil improves Hcy-induced coronary microvascular dysfunction through the PI3K/Akt/eNOS signalling pathway.

The photoisomerization of azobenzene (AZO) makes it a potential type of photoswitch for the field of chemical engineering. However, the lack of stability and photobleaching characteristics of reversible photoisomerization have restricted further application of AZO as a photoswitch. Therefore, we have designed two polymers containing the AZO domain as macromolecular photoswitches and investigated their switching performance. The hydrophilic monomers hydroxyethyl methylacrylate (HEMA) and N-vinyl-2-pyrrolidone (NVP) were chosen to copolymerize with the AZO monomer to form HEMA-AZO copolymer and HEMA-NVP-AZO terpolymer. The domain content was calculated by integration of the peaks in the 1H NMR spectrum. Real-time UV spectra of polymer solutions upon UV light irradiation confirmed quick and successful trans-to-cis transition for the AZO domain. In reverse, the operable and controllable recovery processes upon white light were also verified by real-time UV spectra. Furthermore, repeated irradiation by UV light and white light for 20 times was used to check their fatigue resistance and recyclability. Importantly, recovery behaviors for the two polymers could be adjusted by solvent property, environment temperature, and light intensity. Higher environment temperature or higher light intensity resulted in shortened recovery time. The influence of solvent was only slightly different for the two polymers. Nanoassemblies, which were formed by HEMA-NVP-AZO terpolymer and poly(β-cyclodextrin)/poly(α-cyclodextrin), exhibited similar controllable switching performance to the pure polymer. In brief, the effectiveness and efficiency of the polymers as photoswitches have been confirmed by results in this work.

As the most abundant polysaccharide in lignocellulosic biomass, a clean and renewable carbon resource, cellulose shows huge capacity and roused much attention on the methodologies of its conversion to downstream products, mainly including platform chemicals and fuel additives. Without appropriate treatments in the processes of cellulose decompose, there are some by-products that may not be chemically valuable or even truly harmful. Therefore, higher selectivity and more economical and greener processes would be favored and serve as criteria in a correlational study. Aqueous phase, an economically accessible and immensely potential reaction system, has been widely studied in the preparation of downstream products of cellulose. Accordingly, this mini-review aims at making a related summary about several conversion pathways of cellulose to target products in aqueous phase. Mainly, there are four categories about the conversion of cellulose to downstream products in the following: (i) cellulose hydrolysis hydrogenation to saccharides and sugar alcohols, like glucose, sorbitol, mannose, etc.; (ii) selective hydrogenolysis leads to the cleavage of the corresponding glucose C-C and C-O bond, like ethylene glycol (EG), 1,2-propylene glycol (PG), etc.; (iii) dehydration of fructose and further oxidation, like 5-hydroxymethylfurfural (HMF), 2,5-furandicarboxylic acid (FDCA), etc.; and (iv) production of liquid alkanes via hydrogenolysis and hydrodeoxygenation, like pentane, hexane, etc. The representative products were enumerated, and the mechanism and pathway of mentioned reaction are also summarized in a brief description. Ultimately, the remaining challenges and possible further research objects are proposed in perspective to provide researchers with a lucid research direction.

Traditional contact lenses bring convenience for ophthalmic drug delivery. However, either as contact lenses or as drug carriers, traditional materials have still some drawbacks in the field. Therefore, a transparent film was designed and investigated for the application of therapeutic contact lenses. Chitosan (CS)/graphene oxide (GO) composite film and CS film were fabricated with acceptable transparent and tensile properties by simple casting flow method. Although swelling ratio of CS/GO composite film was higher than that of CS film with significant difference, both formed films had suitable swelling ratio for contact lens application. Both CS/GO composite film and CS film exhibited typical CS infrared characteristic peaks. CS/GO composite film had significant greater breaking strength than CS film, but its elongation at break was a little lower than CS film. Either CS/GO composite film or CS film exhibited good hydrophilic property with a contact angle of around 20 degree. Ofloxacin as a model drug was loaded into films by adsorption diffusion method. Loaded drug amount in CS/GO composite film was a little larger than that in CS film, but without significant difference. The drug release behaviors from CS/GO composite film or CS film were investigated and revealed that the loaded drug could be controlled to release in the first hour. Two kinds of cells were used to evaluate the biocompatibility of films by in vitro method. It was found that both CS/GO composite film and CS film could support human umbilical vein endothelial cell (HUVEC) growth. But for human epidermal fibroblasts (HSF) cells, CS/GO composite film could promote HSF cells growth and proliferation much better than CS film.

Abstract Background Developing an ideal wound dressing that meets the multiple demands of good biocompatibility, an appropriate porous structure, superior mechanical property and excellent antibacterial activity against drug-resistant bacteria is highly desirable for clinical wound care. Biocompatible thermoplastic polyurethane (TPU) membranes are promising candidates as a scaffold; however, their lack of a suitable porous structure and antibacterial activity has limited their application. Antibiotics are generally used for preventing bacterial infections, but the global emergence of drug-resistant bacteria continues to cause social concerns. Results Consequently, we prepared a flexible dressing based on a TPU membrane with a specific porous structure and then modified it with a biomimetic polydopamine coating to prepare in situ a nano-silver (NS)-based composite via a facile and eco-friendly approach. SEM images showed that the TPU/NS membranes were characterized by an ideal porous structure (pore size: ~ 85 μm, porosity: ~ 65%) that was decorated with nano-silver particles. ATR-FITR and XRD spectroscopy further confirmed the stepwise deposition of polydopamine and nano-silver. Water contact angle measurement indicated improved surface hydrophilicity after coating with polydopamine. Tensile testing demonstrated that the TPU/NS membranes had an acceptable mechanical strength and excellent flexibility. Subsequently, bacterial suspension assay, plate counting methods and Live/Dead staining assays demonstrated that the optimized TPU/NS2.5 membranes possessed excellent antibacterial activity against P. aeruginosa, E. coli, S. aureus and MRSA bacteria, while CCK8 testing, SEM observations and cell apoptosis assays demonstrated that they had no measurable cytotoxicity toward mammalian cells. Moreover, a steady and safe silver-releasing profile recorded by ICP-MS confirmed these results. Finally, by using a bacteria-infected (MRSA or P. aeruginosa) murine wound model, we found that TPU/NS2.5 membranes could prevent in vivo bacterial infections and promote wound healing via accelerating the re-epithelialization process, and these membranes had no obvious toxicity toward normal tissues. Conclusion Based on these results, the TPU/NS2.5 nanocomposite has great potential for the management of wounds, particularly for wounds caused by drug-resistant bacteria.

Abstract Background Bacterial infection is one of the most common complications in burn, trauma, and chronic refractory wounds and is an impediment to healing. The frequent occurrence of antimicrobial-resistant bacteria due to irrational application of antibiotics increases treatment cost and mortality. Graphene oxide (GO) has been generally reported to possess high antimicrobial activity against a wide range of bacteria in vitro. In this study, a graphene oxide-quaternary ammonium salt (GO-QAS) nanocomposite was synthesized and thoroughly investigated for synergistic antibacterial activity, underlying antibacterial mechanisms and biocompatibility in vitro and in vivo. Methods The GO-QAS nanocomposite was synthesized through amidation reactions of carboxylic group end-capped QAS polymers with primary amine-decorated GO to achieve high QAS loading ratios on nanosheets. Next, we investigated the antibacterial activity and biocompatibility of GO-QAS in vitro and in vivo. Results GO-QAS exhibited synergistic antibacterial activity against bacteria through not only mechanical membrane perturbation, including wrapping, bacterial membrane insertion, and bacterial membrane perforation, but also oxidative stress induction. In addition, it was found that GO-QAS could eradicate multidrug-resistant bacteria more effectively than conventional antibiotics. The in vitro and in vivo toxicity tests indicated that GO-QAS did not exhibit obvious toxicity towards mammalian cells or organs at low concentrations. Notably, GO-QAS topically applied on infected wounds maintained highly efficient antibacterial activity and promoted infected wound healing in vivo. Conclusions The GO-QAS nanocomposite exhibits excellent synergistic antibacterial activity and good biocompatibility both in vitro and in vivo. The antibacterial mechanisms involve both mechanical membrane perturbation and oxidative stress induction. In addition, GO-QAS accelerated the healing process of infected wounds by promoting re-epithelialization and granulation tissue formation. Overall, the results indicated that the GO-QAS nanocomposite could be applied as a promising antimicrobial agent for infected wound management and antibacterial wound dressing synthesis.

Abstract Diabetes is associated with impaired wound healing, which may be caused primarily by a deficiency in dendritic epidermal T cells (DETCs). In the epidermis, IL-15, IGF-1, and mTOR are known to regulate the maintenance of DETCs; however, it is unclear how these molecules may intersect to regulate DETC homeostasis in diabetes. Here, we show that the reduction of DETCs in the epidermis of diabetic mice is caused by altered homeostasis mediated by a reduction in IL-15 levels. Both impaired mTOR activation and reduction of IL-15 in the epidermis play important roles in DETC homeostasis. Moreover, IGF-1 drives keratinocytes to produce IL-15. The activation of IL-15 is dependent on mTOR, and conversely, mTOR regulates IGF-1 production in DETC, in a classic feedback regulatory loop. Our data suggest that in the setting of diabetes, reduced IGF-1, impaired mTOR pathway activation and reduced IL-15 in the epidermis function coordinately to promote altered DETC homeostasis and delayed skin wound closure.

Backgroud/Aims: The effects of rapamycin (RPM) on wound healing have been previously studied. However, reciprocal contradictory data have been reported, and the underlying mechanism remains unclear. This study aims to uncover differential role of RPM in regulation of wound healing and explore the possible mechanism. Methods: C57BL/6J mice and epidermal cells were treated with different doses of RPM. The wound re-epithelialization was observed by hematoxylin and eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by immunohistochemistry and quantitative real-time PCR. Epidermal cell survival was determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2 pathway were examined by western blot analysis. Results: This study showed that differential doses of RPM could lead to separate consequences in epidermis. Histological analyses showed that low-dose RPM promoted wound healing, and enhanced the expression of IL-15 and IGF-1. Furthermore, western blot analysis showed that the effect of low-dose RPM in epidermis were not through mTORC1 pathway. Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway. Conclusion: This study for the first time demonstrated that RPM-mediated wound healing was dose-dependent.

Background/Aims: In this retrospective study we aimed to compare the effect of tranexamic acid (TXA) vs etamsylate, two hemostatic agents, on hematuria duration in autosomal dominant polycystic kidney disease (ADPKD) patients with persistent gross hematuria. Methods: This is a retrospective study of 40 patients with ADPKD and macroscopic hematuria. 20 patients receiving TXA and snake venom blood clotting enzyme injection were compared with 20 matched patients receiving etamsylate and snake venom blood clotting enzyme injection. The primary outcome was hematuria duration and the secondary outcomes were blood transfusion requirements and adverse events. Results: The hematuria duration was shorter in the TXA group compared with the etamsylate group (4[3-5] d vs 7[6-10] d, P

We demonstrate a hundred micro-Joules level femtosecond laser system based on a compact and simple two-stage Yb:YAG single crystal fiber chirped pulse amplification system which delivers compressed power of 15.57 W, pulse width of 715 fs. The different amplification performance with different input seed power is experimentally studied. A maximum direct amplified power output of 44 W at 100 kHz is obtained for an input seed power of 12 W. To the best of our knowledge, this is the highest average power of femtosecond laser based on single crystal fiber at hundred micro-Joules energy level.

Light-responsive materials have attracted increasing interest in recent years on account of their adjustable on-off properties upon specific light. In consideration of reversible isomerization transition for azobenzene (AZO), it was designed as a light-responsive domain for nanoparticles in this research. At the same time, the interaction between AZO domain and β-cyclodextrin (β-CD) domain was designed as a driving force to assemble nanoparticles, which was fabricated by two polymers containing AZO domain and β-CD domain, respectively. The formed nanoparticles were confirmed by Dynamic Light Scattering (DLS) results and Transmission Electron Microscope (TEM) images. An obvious two-phase structure was formed in which the outer layer of nanoparticles was composed of PCD polymer, as verified by 1HNMR spectroscopy. The efficient and effective light response of the nanoparticles, including quick responsive time, controllable and gradual recovered process and good fatigue resistance, was confirmed by UV-Vis spectroscopy. The size of the nanoparticle could be adjusted by polymer ratio and light irradiation, which was ascribed to its light-response property. Nanoparticles had irreversibly pH dependent characteristics. In order to explore its application as a nanocarrier, drug loading and in vitro release profile in different environment were investigated through control of stimuli including light or pH value. Folic acid (FA), as a kind of target fluorescent molecule with specific protein-binding property, was functionalized onto nanoparticles for precise delivery for anticancer drugs. Preliminary in vitro cell culture results confirmed efficient and effective curative effect for the nanocarrier on MCF-7 cells.

Hydrogels with multifunctional properties attracted intensively attention in the field of tissue engineering because of their excellent performance. Also, object-oriented design had been supposed to an effective and efficient method for material design as cell scaffold in the field of tissue engineering. Therefore, a scaffold-oriented injectable composite hydrogel was constructed by two components. One was pH-sensitive bifunctional nanoparticles for growth factor delivery to improve biofunctionability of hydrogel scaffold. The other was Diels-alder click crosslinked hyaluronic acid hydrogel as matrix. pH dependent release behavior of nanoparticle component was confirmed by results. And, its bioactivity was verified by in vitro cell culture evaluation. In consideration of high-efficiency and effectiveness, low toxicity, controllability and reversibility, dynamic covalent and reversible Diels-alder click chemistry was used to design a HA hydrogel with two kinds of crosslinking points. The properties of hydrogel like gelation time and swelling ratio were influenced by pH value and polymer concentration. Composite hydrogel was formed by in situ polymerization, which exhibited acceptable mechanical property as a scaffold for biomedical field. Lastly, in vitro evaluation from results of viability, DNA content and cell morphology confirmed that hydrogels could maintain cell activity and support cell growth. Compared with pure hydrogel, composite hydrogel possessed better properties.

Azobenzene (AZO) has attracted increasing interest due to its reversible structural change upon a light stimulus. However, poor fatigue durability and the photobleaching phenomenon restricts its further application. Herein, the AZO domain as a pendent group, was incorporated into copolymers, which was synthesized by radical copolymerization in the research. Structure-properties of synthesized copolymer can be adjusted by monomer ratios. Emphatically, responsive properties of copolymer in different solutions were investigated. In the DMSO solution, copolymer exhibited effective structural change, stable rapid responsive time (1 min) upon UV light at room temperature, stable relative acceptable recovery time (100 min) upon white light at room temperature, and good fatigue resistance property. In an aqueous solution, even more controllable responsive properties and fatigue resistance properties for copolymer were verified by results. More pervasively, the recovery process could be controlled by light density and temperature. In order to clarify reasons for the difference between the AZO molecule and the AZO domain of copolymer, energy barrier or interactions between single atoms or even structural units was calculated using the density functional theory (DFT). Furthermore, the status of copolymer was characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Finally, copolymer was further functionalized with bioactive protein (concanavalin, ConA) to reduce the cytotoxicity of the AZO molecule.

The family of graphene has attracted increasing attention on account of their large specific surface area and good mechanical properties in the biomedical field. However, some characteristics like targeted delivery property and drug delivery capacity could not satisfy the need of a drug carrier. Herein, a graphene oxide (GO) nanocarrier was designed by modification of a folic acid (FA) derivative and a β-cyclodextrin (β-CD) derivative in order to improve two properties, respectively. In the first step, reactive or crosslinkable FA and aldehydic β-CD (β-CD-CHO) were designed and synthesized for further modification. In the second step, synthesized functional molecules were coupled onto GO sheets one by one to obtain the GO nanocarrier. IR spectra and XRD results were used to identify the chemical and structural information before and after modification for the GO nanocarrier. The final GO nanocarrier exhibited a typical thin wrinkled sheet morphology of the GO sheet without any influence by two functional molecules. Finally, in vitro evaluation was used to clarify the drug loading and controlling capacity of the nanocarrier as a drug delivery system. The results revealed that the GO nanocarrier had a better CPT loading capacity and showed better controllability for CPT release.

Aqueduct, one kind of bridge structure overpassing a long space, is a significant structure for water delivery for the purpose of agricultural or domestic usage. Aqueduct has quite different loads from other forms of bridges, of which temperature effects due to the environment temperature change, such as seasonal weather or radiation from sunshine, are of great importance. With water flowing inside, the temperature boundary of aqueducts, especially for steel aqueducts, is much more complicated, and relevant researches are limited. In this paper, a 3D Finite Element Method (FEM) simulation process is presented to analyze temperature distribution on the cross-section of a new-type steel truss aqueduct, which belongs to the Water Transfer Project from Yangtze River to Huai River in China. ASHRAE clear-sky model is used to calculate the solar-radiation variation, including direct radiation, diffuse sky radiation, and ground reflected radiation on steel surfaces. The time-dependent sunshine radiation angle of incidence and shielding effect of steel trusses are considered. The water inside the aqueduct is also included in this model, which significantly influences the temperatures of the inner surfaces of the aqueduct. Several temperature distributions under critical conditions of winter and summer are shown in this study, and results of the empty aqueduct under the same circumstances are also provided as a comparison. The effects of wind speed, geographic latitude, and direction of the aqueduct are examined. The conclusions and approach provided by this study could serve as significant references for thermal design and control of similar steel truss aqueducts.

Azobenzene, a photo switcher, has attracted increasing interest due to its structural response to photo stimulus in the field of information science and chemical sensing in the recent decades. However, limited water solubility and cytotoxicity restrained their applications in the biomedical field. In research, HA-AZO has been designed as a water soluble photo switcher in biomedical application. Synthesized HA-AZO had good water-solubility and a stable π-π* transition absorbance peak trans-isomer. With exposure to UV, transformation from trans-isomer to cis-isomer of HA-AZO could be realized according to UV spectra. Reversely, trans-isomer could be gradually recovered from cis-isomer in the dark. Simultaneously, quick response and slow recovery could be detected in the process of structural change. Moreover, repeated illumination was further used to detect the antifatigue property of HA-AZO, which showed no sign of fatigue during 20 circles. The influence of pH value on UV spectrum for HA-AZO was investigated in the work. Importantly, in acid solution, HA-AZO no longer showed any photoresponsive property. Additionally, the status of HA-AZO under the effect of UV light was investigated by DLS results and TEM image. Finally, in vitro cytotoxicity evaluations were performed to show the effects of photoresponsive macromolecule on cells.