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The rapid degradation of magnesium (Mg)-based implants in physiological environment limits its clinical applications, and alloying treatment is an effective way to regulate the degradation rate of Mg-based materials. In the present study, three Mg alloys, including Mg-0.8Ca (denoted as ZQ), Mg-0.8Ca-5Zn-1.5Ag (denoted as ZQ71) and Mg-0.8Ca-5Zn-2.5Ag (denoted as ZQ63), were fabricated by alloying with calcium (Ca), zinc (Zn) and silver (Ag). The results obtained from electrochemical corrosion tests and in vitro degradation evaluation demonstrated that the three Mg alloys exhibited distinct corrosion resistance, and ZQ71 exhibited the lowest degradation rate in vitro among them. After addition of Zn and Ag, the antibacterial potential of Mg alloys was also enhanced. The in vitro cell experiments showed that all the three Mg alloys had good biocompatibility. After implantation in a rat femoral defect, ZQ71 showed significantly higher osteogenic activity and bone substitution rate than ZQ63 and ZQ, due to its higher corrosion resistance as well as the stimulatory effects of the released metallic ions. In addition, the average daily degradation rate of each Mg alloy in vivo was significantly higher than that in vitro, as could be due to the implantation site located in the highly vascularized trabecular region. Importantly, the correlations between the in vitro and in vivo degradation parameters of the Mg alloys were systematically analyzed to find out the potential predictors of the in vivo degradation performance of the materials. The current work not only evaluated the clinical potential of the three biodegradable Mg alloys as bone grafts but also provided a feasible approach for predicting the in vivo degradation behavior of biodegradable materials.

The effect of dams on the longitudinal variability, characteristics, and release mechanism of different nitrogen fractions is unknown along with canyon cascade reservoirs. In this study, we analyze...

The excessive healing response during wound repair can result in hypertrophic scars (HS). Lysyl oxidase like 1 (LOXL1) has been reported to be associated with fibrosis via targeting transforming growth factor β1 (TGF-β1) signaling. This study aimed to investigate the effect of LOXL1 on HS formation. The expression of LOXL1 in HS tissues and TGF-β1-induced HS-derived fibroblasts (HSFs) was detected via reverse transcription quantitative PCR and Western blot. LOXL1 was silenced in HSFs using transfection with short hairpin RNA (shRNA), then wound healing process including cell proliferation, cell cycle distribution, migration, and extracellular matrix (ECM) deposition along with Smad expression were measured by cell counting kit-8, EdU staining, flow cytometry, transwell, immunofluorescence, and Western blot assays. LOXL1 was upregulated in HS tissues and TGF-β1-induced HSFs. Knockdown of LOXL1 inhibited proliferation and migration but promoted cell cycle G0/G1 phase arrest in TGF-β1-induced HSFs; it increased expression of cyclin D1, CDK4, MMP2, MMP9, COL1A1, COL1A2, fibronectin, COL3A1, α-SMA, but decreased expression of p27, and the phosphorylation of Smad2 and Smad3 caused by TGF-β1 were also blocked by LOXL1 silencing. Silence of LOXL1 could effectively inhibit TGF-β1-induced proliferation, migration, and ECM deposition in HSFs via inactivating Smad pathway. Targeting LOXL1 may have future therapeutic implications for HS treatment.

Zeolitic imidazolate frameworks (ZIFs), widely regarded as promising materials for application in catalysis and separation, hold an increasingly significant position in drug delivery systems for their high drug loading capacity. Focused specifically on the rational design of targeting and bioresponsive nanovehicles, a neuropeptide Y1 receptor ligand (Y1L)-modified cell membrane camouflaged bioresponsive ZIF system (Y1L-RBC@ZIF-90@Ce6) was constructed for targeted photodynamic therapy of breast cancer. The biomimetic ZIF-based nanocarrier enhanced tumor accumulation by both neuropeptide Y1 receptor-targeted guidance and long-term stability. Y1L served as a good ligand-mediated selective targeting molecule for breast cancer, and red blood cell membrane-camouflaged nanocomposites displayed favorable biocompatibility. With the dual response of the ZIF to pH and adenosine triphosphate, the stimulus responsive photosensitizer Chlorin e6 delivery system effectively suppressed tumors in vivo. This work offers a platform for developing much safer and more efficient photodynamic therapy for the treatment of Y1R-overexpressed breast cancer.

Leptin is over-secreted in many autoimmune diseases, which can promote dendritic cells (DCs) maturation and up-regulate the expression of inflammatory cytokines, but the underlying mechanisms are not fully elucidated. Considering the major role of leptin in maintaining energy balance and the significant role of glycolysis in DCs activation, our study aims to investigate whether leptin promotes the activation of DCs via glycolysis and its underlying mechanisms. We demonstrated that leptin promoted the activation of DCs, including up-regulating the expression of co-stimulatory molecules and inflammatory cytokines, enhancing the proliferation and T helper 17 (Th17) cell ratio in peripheral blood mononuclear cells (PBMC) co-cultured with leptin-stimulated DCs. Leptin also enhanced DCs glycolysis with increased glucose consumption, lactate production, and the expression of hexokinase 2 (HK2). In addition, the activation of DCs stimulated by leptin could be inhibited by the glycolysis inhibitor 2-deoxy- d -glucose (2-DG). To explore the signaling pathways involved in leptin-induced HK2 expression, we observed that the inhibitors of STAT3 (NSC74859) could repress the enhancement of HK2 triggered by leptin stimulation. Therefore, our results indicated that leptin promoted glycolytic metabolism to induce DCs activation via STAT3-HK2 pathway.

BACKGROUND AND AIMS There is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied. METHODS AND RESULTS We performed a case-control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4-V5 regions), and TMAO was determined via liquid chromatography-tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p

The paper proposes a temperature-compensated sensor for microfluidic application. The sensor consists of a splitter/combiner section with two symmetrical complementary split-ring resonators (CSRR). A polydimethylsiloxane substrate is attached with the microfluidic channel aligned to the meander slot of the CSRR. A split-ring resonator (SRR) with peripheral circuit is added to detect environmental temperature. The water-methanol mixtures with various water fractions are measured at temperature ranging from 20°C to 50°C. The environmental temperature is firstly measured by the resonant frequency shift produced by SRR. Then, the variations in the resonant frequency and quality factor of the differential splitter/combiner section, as well as the temperature, are used as the input data for training the neural network. In comparison with previous designs, the proposed sensor is capable of not only suppressing the influences of environmental factors, but also retrieving the permittivity and loss tangent of liquid sample at specific temperature, thereby identifying the liquid accurately.

4-Hydroxybenzoic acid (4-HBA) is a common organic compound that is prevalent in the environment, and the persistence of 4-HBA residues results in exertion of pollution-related detrimental effects. Bioremediation is an effective method for the removal of 4-HBA from the environment. In this study, two bacterial strains FZ-5 and FZ-8 capable of utilizing 4-HBA as the sole carbon and energy source under anaerobic conditions were isolated from marine sediment samples. Phylogenetic analysis identified the two strains FZ-5 and FZ-8 as Acinetobacter johnsonii and Klebsiella oxytoca, respectively. The strains FZ-5 and FZ-8 degraded 2000 mg·L−1 4-HBA in 72 h with degradation rates of 71.04% and 80.10%, respectively. The optimum culture conditions for degradation by the strains and crude enzymes were also investigated. The strains FZ-5 and FZ-8 also exhibited the ability to degrade other lignin-derived compounds, such as protocatechuic acid, cinnamic acid, and vanillic acid. Immobilization of the two strains showed that they could be used for the bioremediation of 4-HBA in an aqueous environment. Soils inoculated with the strains FZ-5 and FZ-8 showed higher degradation of 4-HBA than the uninoculated soil, and the strains could survive efficiently in anaerobic soil. This is the first report of 4-HBA-degrading bacteria, belonging to the two genera, which showed degradation ability under anaerobic conditions. This study expound the strains could efficiently degrade 4-HBA in anaerobic soil and will help in the development of 4-HBA anaerobic bioremediation systems.

Objective: We aimed to develop a novel anti-HIF-1α intrabody to decrease gemcitabine resistance in pancreatic cancer patients. Methods: Surface plasmon resonance and glutathione S-transferase pull-down assays were conducted to identify the binding affinity and specificity of anti-HIF-1α VHH212 [a single-domain antibody (nanobody)]. Molecular dynamics simulation was used to determine the protein-protein interactions between hypoxia-inducible factor-1α (HIF-1α) and VHH212. The real-time polymerase chain reaction (PCR) and Western blot analyses were performed to identify the expressions of HIF-1α and VEGF-A in pancreatic ductal adenocarcinoma cell lines. The efficiency of the VHH212 nanobody in inhibiting the HIF-1 signaling pathway was measured using a dual-luciferase reporter assay. Finally, a PANC-1 xenograft model was developed to evaluate the anti-tumor efficiency of combined treatment. Immunohistochemistry analysis was conducted to detect the expressions of HIF-1α and VEGF-A in tumor tissues. Results: VHH212 was stably expressed in tumor cells with low cytotoxicity, high affinity, specific subcellular localization, and neutralization of HIF-1α in the cytoplasm or nucleus. The binding affinity between VHH212 and the HIF-1α PAS-B domain was 42.7 nM. Intrabody competitive inhibition of the HIF-1α heterodimer with an aryl hydrocarbon receptor nuclear translocator was used to inhibit the HIF-1/VEGF pathway in vitro. Compared with single agent gemcitabine, co-treatment with gemcitabine and a VHH212-encoding adenovirus significantly suppressed tumor growth in the xenograft model with 80.44% tumor inhibition. Conclusions: We developed an anti-HIF-1α nanobody and showed the function of VHH212 in a preclinical murine model of PANC-1 pancreatic cancer. The combination of VHH212 and gemcitabine significantly inhibited tumor development. These results suggested that combined use of anti-HIF-1α nanobodies with first-line treatment may in the future be an effective treatment for pancreatic cancer.

Light may participate in biocatalytic processes either by direct light-induced biocatalysis or by cascading light-induced chemical reactions with biocatalytic ones, which are acknowledged as photocatalysis. As it combines the strength of chemocatalysis and biocatalysis, photobiocatalysis provides attractive advantages towards green synthesis in terms of atom efficiency, selectivity and promiscuity. Particularly, photobiocatalysis has demonstrated its unique power in C–H bond functionalization. Versatile approaches, mostly via combining photocatalytic and biocatalytic processes in one pot, have been developed to synthesize a broad range of valuable compounds. The reactions include hydroxylation, halogenation, amination and ring-expansion of C–H bonds. In this mini-review, we critically summarize recent advances of photocatalytic C–H bond functionalization by combining photocatalysts and enzymes in cascade reactions, in hope that the advantages and potentials offered by photobiocatalysis will trigger further enthusiasm in the research field of light-induced cascade reactions.

Background As one of the major components of lignocellulosic biomass, lignin has been considered as the most abundant renewable aromatic feedstock in the world. Comparing with thermal or catalytic strategies for lignin degradation, biological conversion is a promising approach featuring with mild conditions and diversity, and has received great attention nowadays. Results In this study, a consortium of white rot fungi composed of Lenzites betulina and Trametes versicolor was employed to enhance the ligninolytic enzyme activity of laccase (Lac) and manganese peroxidase (MnP) under microbial synergism. The maximum enzymatic activity of Lac and MnP was individually 18.06 U mL−1 and 13.58 U mL−1 along with a lignin degradation rate of 50% (wt/wt), which were achieved from batch cultivation of the consortium. The activities of Lac and MnP obtained from the consortium were both improved more than 40%, as compared with monocultures of L. betulina or T. versicolor under the same culture condition. The enhanced biodegradation performance was in accordance with the results observed from scanning electron microscope (SEM) of lignin samples before and after biodegradation, and secondary-ion mass spectrometry (SIMS). Finally, the analysis of heteronuclear single quantum coherence (HSQC) NMR and gas chromatography–mass spectrometry (GC–MS) provided a comprehensive product mapping of the lignin biodegradation, suggesting that the lignin has undergone depolymerization of the macromolecules, side-chain cleavage, and aromatic ring-opening reactions. Conclusions Our results revealed a considerable escalation on the enzymatic activity obtained in a short period from the cultivation of the L. betulina or T. versicolor due to the enhanced microbial synergistic effects, providing a potential bioconversion route for lignin utilization.

Cationic surfactants have a strong affinity to sorb to phospholipid membranes and thus possess an inherent potential to bioaccumulate, but there are few measurements of bioconcentration in fish. We measured the bioconcentration of 10 alkylamines plus two quaternary ammonium compounds in juvenile rainbow trout at pH 7.6, and repeated the measurements at pH 6.2 for 6 of these surfactants. The BCF of the amines with chain lengths ≤ C14 was positively correlated with chain length, increasing ∼0.5 log units per carbon. Their BCF was also pH dependent and approximately proportional to the neutral fraction of the amine in the water. The BCFs of the quaternary ammonium compounds showed no pH dependence and were >2 orders of magnitude less than for amines of the same chain length at pH 7.6. This indicates that systemic uptake of permanently charged cationic surfactants is limited. The behavior of the quaternary ammonium compounds and the two C16 amines studied was consistent with previous observations that these surfactants accumulate primarily to the gills and external surfaces of the fish. At pH 7.6 the BCF exceeded 2000 L kg–1 for 4 amines with chains ≥ C13, showing that bioconcentration can be considerable for some longer chained cationic surfactants., Bioconcentration of cationic surfactants depends on pH and alkyl chain length, with BCFs up to 8200 L kg−1 observed.

A low-power-consumption single-arm-driven silicon (Si) Mach-Zehnder modulator (MZM) operated at C-band ( $\lambda =1550$ nm) for non-return-to-zero on-off-keying (NRZ-OOK) transmission beyond 50 Gbit/s over 10-km single-mode fiber (SMF) and dispersion-shift fiber (DSF) is demonstrated to guarantee the IEEE 802.3bs standardized 400GBASE-FR8/LR8 operation. The Si MZM exhibits asymmetric waveguide arms and 2-mm-contact-length phase shifter under carrier depletion operation in its p-n junction, which is DC biased as low as 2 V to provide a low $\text{V}_{\pi }\text{L}$ product of $0.909~\text {V}\cdot \text {cm}$ . For the error-free transmission of the NRZ-OOK data-stream, the single-arm-driven Si MZM supports the highest data rates of 53, 53 and 50 Gbit/s over optical back-to-back, 2-km SMF and 10-km DSF transmissions, respectively. The 50-Gbit/s receiving power penalties are respectively 0.2 and 0.25 dB after 2-km SMF and 10-km DSF propagation.

Purpose: To determine the potential effect of total flavonoids from Drynaria rhizome on bone loss in ovariectomized (OVX) rats. Methods: The rats were divided into four groups: normal control, ovariectomized (OVX) control, and two Drynaria rhizome (DR) flavonoids treatments. Post-operation, osteoporotic OVX rats were given Drynaria rhizome total flavonoids for 3 months. Thereafter, the expressions of bone-related genes and biochemical indices were investigated in samples taken from rat serum and bone. Results: Treatment with total flavonoids from Drynaria rhizome prevented bone mineral loss and improved some related biochemical indices associated with osteoporosis, namely, alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), bone gla protein (BGP) and estradiol (E2). Reverse transcription-polymerase chain reaction (RT-PCR) data showed that treatment with the total flavonoids significantly downregulated mRNA expression of Wnt10b, β-catenin, recombinant human bone morphogenetic protein-2 (BMP2) and BMP4 in OVX rats, but significantly reversed OVX-induced downregulation of dickkopf1 (Dkk1) mRNA expression. Conclusion: These results indicate that total flavonoids from Drynaria rhizome exert anti-osteoporotic effects in rats through the WNT signaling and BMP-2 signaling pathways.

Purpose: To optimize the extraction parameters for total flavonoids of Drynaria rhizome, and determine their effect on osteoclast differentiation and bone resorption in vitro. Methods: A 5-level 3-factor central composite design was applied to the optimization of extract yield of total flavonoids from Drynaria rhizome. Response Surface Methodology (RSM) design was used to optimize total flavonoids extraction from Drynaria rhizome. The independent factors included extraction temperature (A), extraction time (B) and liquid: solid ratio (C). Moreover, NFATc1, DC-STAMP, cathepsin K and MMP-9 mRNA expressions were determined. Results: Values obtained were fitted into a second-order polynomial equation with multiple regression analysis using a statistical method. Analysis of variance results indicate that the independent variables influenced total flavonoid extraction from Drynaria rhizome. The optimal conditions for extraction yield were extraction temperature of 75 oC, extraction time of 100 min, and liquid: solid ratio of 107:1. The yield of 5.38 ± 0.62 % was consistent with these optimized conditions, which was an indication of the accuracy of the model. Experiments revealed that total flavonoids from Drynaria rhizome regulated the expression levels of NFATc1, DC-STAMP, cathepsin K and MMP-9 mRNA Conclusion: This study has successfully optimized the extraction yield of total flavonoids from Drynaria rhizome. The total flavonoids inhibit osteoclast differentiation and bone resorption. Thus, they may be beneficial in the treatment of bone diseases.

Dialysis patients with erythropoietin hypo-responsiveness suffered from refractory anemia. Roxadustat reversibly binds and inhibits hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD), resulting in increased endogenous EPO which stimulates erythropoiesis, theoretically has an advantage over exogenous EPO in anti-anemia therapy. From September 2019 to October 2020, 32 dialysis patients with hypo-responsiveness to erythropoietin were evaluated. During the 24-week follow-up period, all patients were taken off erythropoietin and switched to roxadustat. Dosage adjustments were administrated according to the fluctuation of hemoglobin level during the treatment. Parameters about anemia, iron metabolism and biochemical indexes were collected, and adverse events were recorded. A total of 31 patients completed the clinical observation, with varying degrees of malnutrition-inflammation. Post treatment, the levels of transferrin and total iron-binding capacity were increased, while that of transferrin saturation and cholesterol decreased. 15 cases (accounting for 48.39%, designated as fulfilled group) met the target level of hemoglobin, while 16 cases (51.61%, non-fulfilled group) did not. The baseline conditions of the above two groups were compared. The levels of hypersensitive C-reactive protein, interleukin-6 and serum ferritin in the non-fulfilled group were higher than those in the fulfilled group, and the levels of residual renal function, serum albumin, iron, transferrin and total iron-binding capacity were lower than those in the fulfilled group. Linear regression analysis showed that increase of HsCRP had a negative effect on the improvement of Hb. One case of adverse reaction grade 3 and four cases of grade 2 occurred throughout the study, yet all were relieved after therapy. Significant anti-anemia effects could be achieved in most patients with erythropoietin hypo-responsiveness after treatment with roxadustat, accompanied by relatively mild and rare adverse reactions. The malnutrition-inflammation states of patients may interfere with the anti-anemia effect of roxadustat, and iron utilization is more important than iron storage in anemia improvement.

In industry, tape casting is an important way for the preparation of polymer thin films. Because the velocity and temperature controls in the casting process are related to the final quality of the film, this paper studies the flow and heat transfer behaviors of producing ethylene vinyl acetate (EVA) nanofluid film by tape casting. Rheological experiment shows that the melted EVA (28% VA) is a power-law fluid. According to the similar principle of momentum transfer and energy transfer, the modified Fourier’s law is presented. And then, the corresponding new convective heat transfer equation has been established. Moreover, a power-law velocity slip model, which is well suited for describing the slip characteristics of polymer films, has been newly developed. With the skillful inverse variable transformation, the analytical solutions of velocity and temperature at any time and space are first presented. It is noteworthy that the heat transfer rate of power-law fluid is weaker than that of Newtonian fluid. Furthermore, it is observed that the temperature is reduced with the enhancement of both temperature control parameter d and the convective heat transfer coefficient $$h_{0}$$ , which can ensure the best cooling effect.

Study design Western blot, reverse transcription-polymerase chain reaction (RT-PCR), radiological, and histological analyses of the rat ossification of ligamentum flavum (OLF) induced by cyclic tensile stress. Objective The aim of this study was to induce the OLF using cyclic tensile stress to rat thoracolumbar ligamentum flavum, and to investigate the possible molecular mechanism of tension-induced OLF. Summary of background data Tensile stress has been considered as an important factor leading to the OLF. So far, however, no OLF induced by tension has been reported. Methods Forty rats were randomly divided into five equal groups. For control groups, the blank and anesthesia groups were not subjected to tension. For experimental groups, the 4-, 8-, and 12-week groups were subjected to cyclic tensile stress of ligamentum flavum after abdominal anesthesia for 4 weeks, 8 weeks, and 12 weeks, respectively, using an original stress apparatus for rats. The radiological and morphological changes of rat spine, as well as the protein and mRNA expressions of CD44, bone morphogenetic protein-2 (BMP-2), integrin β3, collagen protein type I (COL1), osteopontin (OPN), runt-related transcription factor 2 (RUNX-2), and vascular endothelial growth factor (VEGF), were concerned. Results The micro-CT showed OLF in the 4-, 8-, and 12-week group. The axial maximum occupied area of ossifications was 1.42 mm2, 3.35 mm2, and 7.28 mm2, respectively. In histopathology, chondrocytes proliferated in the experimental model; woven bone arose in the 8- and 12-week groups, and was more noticeable in the 12-week group. According to western blot and RT-PCR, the expressions of seven osteogenesis-related molecules were all increased in three experimental groups. Conclusion Cyclic tensile stress to the ligamentum flavum in rats can induce the OLF, and the longer the duration, the more visible the osteogenesis. The upregulation and synergism of osteogenesis-related molecules may contribute to the OLF induced by tensile stress.Level of Evidence: N/A.

The effect of high pressure processing (HPP, 600 MPa, 5 min) and thermal treatment (85 °C, 15 min) on aronia berry juice in a pilot scale was studied. The maximal shelf-life of treated samples at room temperature (RT, approximately 25 °C) or refrigerated storage (RS, 4 °C) was also investigated. Microbial counts, physicochemical properties, enzymes activities, phenolic compounds, and antioxidant activities of these juices were determined and compared. Results indicated that HPP treatment improved the microbial shelf-life of the aronia juice by at least 10-times at RT and 5-times at RS. Although thermal treatment was equally effective in extending the shelf-life, the high temperature resulted in a quicker degradation of polyphenols in aronia juice, which was decreased by 36.6% during RT storage (5 weeks) and 43.3% at RS storage (24 weeks). Therefore, HPP was more efficient in maintaining the safety and quality of aronia juice. The study also indicated HPP treated aronia juice could be stored at RT for at least one month that could be of benefit to the non-cold chain process which is targeting for a low-energy input while still retaining a minimal effect on the nutritional properties of food products.

Liver sinusoidal endothelial cells (LSECs), which play a very critical role in liver regeneration, function in hypoxic environments, but few studies have elucidated the specific mechanism. As a hypoxia-sensitive gene, Sentrin/SUMO-specific protease 1(SENP1) is upregulated in solid tumors due to hypoxia and promotes tumor proliferation. We speculate that LSECs may upregulate SENP1 in hypoxic environments and that SENP1 may act on downstream genes to allow the cells to adapt to the hypoxic environment. To elucidate the reasons for the survival of LSECs under hypoxia, we designed experiments to explore the possible mechanism. First, we cultured murine LSECs in hypoxic conditions for a certain time (24 h and 72 h), and then, we observed that the proliferation ability of the hypoxia group was higher than that of the normoxia group, and the number of unique fenestrae of the LSECs in the hypoxia group was more than that of the LSECs in the normoxia group. Then, we divided the LSECs into several groups for hypoxic culture for time points (6 h, 12 h, 24 h, 36 h, and 72 h), and we found that the expression of SENP1, HIF-1α and VEGF was significantly upregulated. Then, we silenced SENP1 and HIF-1α with si-SENP1 and si–HIF–1α, respectively. SENP1, HIF-1α and VEGF were significantly downregulated, as determined by RT-PCR, WB and ELISA. Unexpectedly, the proliferation activity of the LSECs decreased and the fenestrae disappeared more in the si-SENP1 and si–HIF–1α groups than in the control group. It is concluded that LSECs cultured under hypoxic conditions may maintain fenestrae and promote proliferation through the SENP1/HIF-1α/VEGF signaling axis, thereby adapting to the hypoxic environment.

Recent discoveries of two-dimensional transitional metal based materials have emerged as an excellent candidate for fabricating nanostructured flame-retardants. Herein, we report an eco-friendly flame-retardant for flexible polyurethane foam (PUF), which is synthesised by hybridising MXene (Ti$$_3\hbox {C}_2$$ 3 C 2 ) with biomass materials including phytic acid (PA), casein, pectin, and chitosan (CH). Results show that coating PUFs with 3 layers of CH/PA/Ti$$_3\hbox {C}_2$$ 3 C 2 via layer-by-layer approach reduces the peak heat release and total smoke release by 51.1% and 84.8%, respectively. These exceptional improvements exceed those achieved by a CH/Ti$$_3\hbox {C}_2$$ 3 C 2 coating. To further understand the fundamental flame and smoke reduction phenomena, a pyrolysis model with surface regression was developed to simulate the flame propagation and char layer. A genetic algorithm was utilised to determine optimum parameters describing the thermal degradation rate. The superior flame-retardancy of CH/PA/Ti$$_3\hbox {C}_2$$ 3 C 2 was originated from the shielding and charring effects of the hybrid MXene with biomass materials containing aromatic rings, phenolic and phosphorous compounds.

A bioanalytical method for simultaneous quantification of isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB) in plasma was developed and validated using high-performance liquid chromatography with tandem mass spectrometry. After extracted by protein precipitation with acetonitrile, the analytes were separated on a Waters XBridge Amide column by isocratic elution with acetonitrile and 5 mM ammonium acetate solution containing 0.3% formic acid (77:23, v/v) at a flow rate of 0.5 mL/min. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source in positive mode by monitoring the selected ion transitions at m/z 205.2 → 116.1, m/z 137.9 → 121.2, m/z 124.3 → 78.9 and m/z 213.1 → 122.4 for EMB, INH, PZA and EMB-d8 Internal standard (IS), respectively. The calibration curves were linear over the range of 0.0125–2.00 μg/mL for EMB, 0.0625–10.0 μg/mL for INH and 0.250–40.0 μg/mL for PZA. Neither cross-analytes inter-conversion nor matrix effects were observed. The intra- and inter-assay precision (%RSD) values were within 8.80%, and accuracy (%RE) ranged from −11.13 to 13.49%, indicating that the precision and accuracy were well within the acceptable limits of variation. The method would be helpful for analysis of EMB, INH and PZA in plasma samples from clinical pharmacokinetics and therapeutic drug monitoring.

Plant defense against heat stress involves adjustments in amino acid metabolism. The objective of this study was to identify major amino acids and associated metabolic pathways differentially regulated by γ-aminobutyric acid (GABA) and proline that may contribute to augmentation of heat tolerance in cool-season grass species. Creeping bentgrass (Agrostis stolonifera L. cv. ‘Penncross’) was exposed to non-stress (22/18 °C, day/night) or heat stress (35/30 °C, day/night) conditions for 35 d in controlled-environment growth chambers. Non-stressed and heat-stressed plants were foliar-sprayed with water (untreated control), GABA, proline, or ammonium nitrate (N) as a nitrogen source control. Under heat stress, foliar application of GABA, proline, or N significantly increased turf quality and leaf chlorophyll content compared to untreated control plants. N application had nutritional effects, resulting in increases in the content of all amino acids under heat stress. Application of GABA under heat stress significantly increased endogenous content of glutamic acid, GABA, and threonine. Plants treated with proline under heat stress had significantly higher endogenous levels of proline, GABA, glutamic acid, aspartic acid, lysine, isoleucine, leucine, valine, serine, alanine, threonine, and tryptophan compared to untreated controls. The improved heat tolerance in creeping bentgrass pathway by GABA was mainly associated with regulation of amino acid metabolism in the GABA shunt and oxaloacetate pathways. Proline-enhanced heat tolerance involved the regulation of five metabolic pathways (GABA shunt, oxaloacetate, 3-phosphoglycerate, secondary metabolism, and pyruvate). GABA and proline, as well as their responsive amino acids could be used as biomarkers to improve heat tolerance in cool-season grass species.

Unlike stable atherosclerotic plaques, vulnerable plaques are very likely to cause serious cardio-cerebrovascular diseases. Meanwhile, how to non-invasively identify vulnerable plaques at early stages has been an urgent but challenging problem in clinical practices. Here, we propose a macrophage-targeted and in situ stimuli-triggered T1–T2 switchable magnetic resonance imaging (MRI) nanoprobe for the non-invasive diagnosis of vulnerable plaques. Precisely, single-dispersed iron oxide nanoparticles (IONPs) modified with hyaluronic acid (HA), denoted as IONP-HP, show macrophage targetability and T1 MRI enhancement (r2/r1 = 3.415). Triggered by the low pH environment of macrophage lysosomes, the single-dispersed IONP-HP transforms into a cluster analogue, which exhibits T2 MRI enhancement (r2/r1 = 13.326). Furthermore, an in vivo switch of T1–T2 enhancement modes shows that the vulnerable plaques exhibit strong T1 enhancement after intravenous administration of the nanoprobe, followed by a switch to T2 enhancement after 9 h. In contrast, stable plaques show only slight T1 enhancement but without T2 enhancement. It is therefore imperative that the intelligent and novel nanoplatform proposed in this study achieves a substantial non-invasive diagnosis of vulnerable plaques by means of a facile but effective T1–T2 switchable process, which will significantly contribute to the application of materials science in solving clinical problems.

Leaf senescence is accelerated by prolonged exposure to high temperatures in cool-season plants and is characterized by loss of chlorophyll and adjustment in amino acid metabolism. The objectives of this study included ascertaining how glutamate may affect the tolerance of cool-season grass species to heat stress in relation to leaf senescence through the regulation of leaf chlorophyll (Chl) and amino acid metabolism. Creeping bentgrass (Agrostis stolonifera L.) plants were maintained for 35d under optimal growth temperature (22/18 °C, day/night, non-stress control) or heat stress (35/30 °C, day/night) in growth chambers, and glutamate (60 mM) or water (untreated control) was applied weekly as a foliar treatment. Under heat stress, turf quality (TQ), photochemical efficiency (Fv/Fm), and Chl content were significantly higher in plants treated with glutamate at 14-35 d, 7-28 d, and 7-35 d, respectively, compared to untreated controls. Glutamate application significantly reduced the activities of chlorophyll-degrading peroxidase and chlorophyllase, two Chl-degrading enzymes, at 14, 21, and 35 d of heat stress, whereas activity of the rate-limiting Chl synthesis enzyme, porphobilinogen deaminase, was not significantly affected. Glutamate treatment significantly increased the endogenous content of serine, threonine, lysine, aspartate, glutamate, and GABA under heat stress, while methionine, asparagine, isoleucine, and histidine were significantly up-regulated exclusively under heat stress. These findings suggest that glutamate could serve as a repressor for heat-accelerated leaf senescence by suppressing Chl degradation and activating amino acid metabolism involved in energy production, antioxidant defense, and nitrogen balance.

Nerve agents always pose a serious threat to human safety and health as a result of their extremely high toxicity and convenient transport, which has prompted much effort to develop some methods with fast response and high selectivity for detecting nerve agents. Herein, we designed and synthesized two simple rhodamine phenol-based derivatives (RBNP and RBMP). From spectral experiments, we found that RBNP exhibited a significant change of absorption and fluorescence intensity with the nerve agent simulant diethylchlorophosphate (DCP), which could give rise to a fast response within 10 s and high sensitivity with an extremely low detection limit of 1.4 nM in the solution. The sensing mechanism could be attributed to it forming a stable five-membered ring by intramolecular bonding under protonation on the basis of experimental and theoretical calculations. Furthermore, test strips were successfully prepared by immersing TLC plates into the probe RBNP solution and these also achieved a visual system for detecting GB vapor. Therefore, a fast and convenient prospective test method is reported for visually detecting real nerve agents.

Despite remarkable clinical achievements, camptothecin (CPT) still suffers from poor solubility and severe toxicity. Therefore, it is necessary to redevelop CPT derivatives as supplementary antitumor agents with good water solubility and small side effects. In this work, 27 camptothecin derivatives were synthesized and screened for their cytotoxicity against A549 (lung) and HCT-116 (colon) cancer cell lines. Among them, compound B7, 7-ethyl-10-(2-oxo-2-(4-methylpiperidin-1-yl)ethoxy)camptothecin,was demonstrated in vitro to be a more potent antitumor agent than SN-38 by comparison of their inhibitory activities against cell proliferation and colony formation and interference effect on process of cell cycle and cell apoptosis. Additionally, a molecular docking model revealed that B7 can interact with the topoisomerase I-DNA complex, and that the solubility of B7 reached 5.73 μg/mL in water. Moreover, B7 significantly inhibited tumor growth in an A549 xenograft model at dosages of 0.4 and 2.0 mg/kg, and exhibited minimum lethal doses comparable to those of irinotecan. These results indicated that B7, with improved solubility, enhanced activity and acceptable acute toxicity, can be used as a lead compound for the development of novel anticancer agents.

Background: Pancreatic cancer (PC) is a leading cause of cancer-related deaths worldwide. Human leukocyte antigen complex P5 (HCP5), a member of long noncoding RNAs (lncRNAs), was reported to be associated with the poor prognosis of PC. However, the mechanism of HCP5 in regulating the progression of PC remains poorly defined. Materials and Methods: Quantitative real-time polymerase chain reaction was performed to detect the expression levels of HCP5, microRNA (miR)-140-5p, and cyclin-dependent kinase 8 (CDK8) in PC tissues and cells. Cell counting kit-8 (CCK-8) assay was utilized to check cell proliferation. Transwell assay was employed to evaluate the abilities of cell migration and invasion. Xenograft tumor model was established to investigate the biological role of HCP5 in PC in vivo. The interaction between miR-140-5p and HCP5 or CDK8 was predicted by starBase or TargetScan, respectively. The dual-luciferase reporter assay was conducted to corroborate the interaction. The protein level of CDK8 was measured by Western blot. Results: HCP5 and CDK8 were significantly upregulated in PC tissues and cells, opposite to the expression of miR-140-5p. High expression of HCP5 contributed to the low survival rate and HCP5 silencing inhibited proliferation, migration, and invasion of PC cells in vitro. Simultaneously, in vivo experiments indicated that downregulation of HCP5 suppressed tumor growth. In addition, miR-140-5p was a target of HCP5 and bound to the 3'-untranslated region (3'UTR) of CDK8. Further studies revealed that overexpression of CDK8 reversed the miR-140-5p-mediated inhibitory effect on PC progression. Moreover, downregulation of miR-140-5p or upregulation of CDK8 inverted the silencing-mediated repressive impact of HCP5 on PC progression. Conclusion: Downregulation of HCP5 impeded PC progression by downregulating CDK8 via sponging miR-140-5p.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a devastating condition that affects neurodevelopment and results in brain injury in infants. Morroniside (MOR), a natural secoiridoid glycoside, has been found to possess neuroprotective effect. However, the effects of MOR on neonatal HIE are unclear. An