α-Lys424 Participates in Insertion of FeMoco to MoFe Protein and Maintains Nitrogenase Activity in Klebsiella oxytoca M5al

Our previous investigation of substrates reduction catalyzed by nitrogenase suggested that α-Ile423 of MoFe protein possibly functions as an electron transfer gate to Mo site of active center-“FeMoco”. Amino acid residue α-Lys424 connects directly to α-Ile423, and they are located in the same α-helix (α423-431). In the present study, function of α-Lys424 was investigated by replacing it with Arg (alkaline, like Lys), Gln (neutral), Glu (acidic), and Ala (neutral) through site-directed mutagenesis and homologous recombination. The mutants were, respectively, termed 424R, 424Q, 424E, and 424A. Studies of diazotrophic cell growth, cytological, and enzymatic properties indicated that none of the substitutions altered the secondary structure of MoFe protein, or normal expression of nifA, nifL, and nifD. Substitution of alkaline amino acid (i.e., 424R) maintained acetylene (C2H2) and proton (H+) reduction activities at normal levels similar to that of wild-type (WT), because its FeMoco content did not reduce. In contrast, substitution of acidic or neutral amino acid (i.e., 424Q, 424E, 424A) impaired the catalytic activity of nitrogenase to varying degrees. Combination of MoFe protein structural simulation and the results of a series of experiments, the function of α-Lys424 in ensuring insertion of FeMoco to MoFe protein was further confirmed, and the contribution of α-Lys424 in maintaining low potential of the microenvironment causing efficient catalytic activity of nitrogenase was demonstrated

Enhanced Hemostatic Performance of Tranexamic Acid-Loaded Chitosan/Alginate Composite Microparticles

Novel microparticles based on chitosan and sodium alginate were prepared using emulsification and cross-linking technologies. The spherical microparticles had a porous surface and a diameter of 2~40 μm. In simulated body fluid, these microparticles quickly swelled but gradually degraded. The results of the MTT assay revealed that a slight inhibition of cell proliferation was observed on day 2 and then gradually decreased afterward. No cell morphology changes were observed. By loading tranexamic acid, the hemostatic performance of the microparticles was obviously improved. Using fast-acting styptic powder (Flashclot) as the control, the hemostatic efficiency was investigated in rabbits using a liver transection bleeding model. It was found that both Flashclot and the microparticles achieved hemostasis in 3.07±0.84 min and 2.48±0.88 min, respectively; however, the tranexamic acid-loaded microparticles stopped the bleeding in 1.90±0.75 min (P<0.05). Additionally, Flashclot resulted in heat injury to the experimental livers, while the microparticles did not. Thus, with their biodegradability, safety, and superior hemostatic efficiency, tranexamic acid-loaded microparticles might be a promising new powdered hemostatic agent with a wide range of potential applications

Achieving near-infrared-light-mediated switchable friction regulation on MXene-based double network hydrogels

Abstract MXene possesses great potential in enriching the functionalities of hydrogels due to its unique metallic conductivity, high aspect ratio, near-infrared light (NIR light) responsiveness, and wide tunability, however, the poor compatibility of MXene with hydrogels limits further applications. In this work, we report a uniformly dispersed MXene-functionalized poly-N-isopropylacrylamide (PNIPAM)/poly-2-acrylamido-2-methyl-1-propanesulfonic acid (PAMPS) double network hydrogel (M—DN hydrogel) that can achieve switchable friction regulation by using the NIR light. The dispersity of MXene in hydrogels was significantly improved by incorporating the chitosan (CS) polymer. This M—DN hydrogel showed much low coefficient of friction (COF) at 25 °C due to the presence of hydration layer on hydrogel surface. After illuminating with the NIR light, M—DN hydrogel with good photothermal effect rapidly raised the temperature to above the lower critical solution temperature (LCST), which led to an obvious increase of surface COF owing to the destruction of the hydration layer. In addition, M—DN friction control hydrogel showed good recyclability and controllability by tuning “on-off” of the NIR light. This work highlights the construction of functional MXene hydrogels for intelligent lubrication, which provides insight for interface sensing, controlled transmission, and flexible robotic arms

Learning Motion Constraint-Based Spatio-Temporal Networks for Infrared Dim Target Detections

Efficient infrared dim object detection has been challenged by low signal-to-noise ratios (SNRs). Traditional methods rely on the gradient difference and fixed-parameter model. These methods fail to adapt to sophisticated and variable situations in the real world. To tackle the issue, a deep learning method based on the spatio-temporal network is proposed in this paper. The model is established by the Convolutional Long Short-Term Memory cell (Conv-LSTM) and the 3D Convolution cell (3D-Conv). It is trained to learn the motion constraint of moving targets (spatio-temporal constraint module, called STM) and to fuse the multiscale local feature between the target and background (deep spatial features module, called DFM). In addition, a variable interval search module (state-aware module, called STAM) is added to the inference. The submodule decides to conduct a global search for images only if the target is lost due to fast motion, uncertain obstruction, and frame loss. Comprehensive experiments indicate that the proposed method achieves better performance over all baseline methods. On the mid-wave infrared datasets collected by the authors, the proposed method achieves a 95.87% detection rate. The SNR of the dataset is around 1&ndash;3 dB, and the background of the sequence includes sky, asphalt road, and buildings

Learning Motion Constraint-Based Spatio-Temporal Networks for Infrared Dim Target Detections

Efficient infrared dim object detection has been challenged by low signal-to-noise ratios (SNRs). Traditional methods rely on the gradient difference and fixed-parameter model. These methods fail to adapt to sophisticated and variable situations in the real world. To tackle the issue, a deep learning method based on the spatio-temporal network is proposed in this paper. The model is established by the Convolutional Long Short-Term Memory cell (Conv-LSTM) and the 3D Convolution cell (3D-Conv). It is trained to learn the motion constraint of moving targets (spatio-temporal constraint module, called STM) and to fuse the multiscale local feature between the target and background (deep spatial features module, called DFM). In addition, a variable interval search module (state-aware module, called STAM) is added to the inference. The submodule decides to conduct a global search for images only if the target is lost due to fast motion, uncertain obstruction, and frame loss. Comprehensive experiments indicate that the proposed method achieves better performance over all baseline methods. On the mid-wave infrared datasets collected by the authors, the proposed method achieves a 95.87% detection rate. The SNR of the dataset is around 1–3 dB, and the background of the sequence includes sky, asphalt road, and buildings

Microbial diversity patterns in the root zone of two Meconopsis plants on the Qinghai-Tibet Plateau

In the extreme alpine climate of the Qinghai-Tibet Plateau (QTP), plant growth and reproduction are limited by extremely cold temperatures, low soil moisture, and scarce nutrient availability. The root-associated microbiome indirectly promotes plant growth and plays a role in the fitness of plants on the QTP, particularly in Tibetan medicinal plants. Despite the importance of the root-associated microbiome, little is known about the root zone. This study used high-throughput sequencing to investigate two medicinal Meconopsis plants, M. horridula and M. integrifolia, to determine whether habitat or plant identity had a more significant impact on the microbial composition of the roots. The fungal sequences were obtained using ITS-1 and ITS-2, and bacterial sequences were obtained using 16S rRNA. Different microbial patterns were observed in the microbial compositions of fungi and bacteria in the root zones of two Meconopsis plants. In contrast to bacteria, which were not significantly impacted by plant identity or habitat, the fungi in the root zone were significantly impacted by plant identity, but not habitat. In addition, the synergistic effect was more significant than the antagonistic effect in the correlation between fungi and bacteria in the root zone soil. The fungal structure was influenced by total nitrogen and pH, whereas the structure of bacterial communities was influenced by soil moisture and organic matter. Plant identity had a greater influence on fungal structure than habitat in two Meconopsis plants. The dissimilarity of fungal communities suggests that more attention should be paid to fungi-plant interactions

Effects of Traditional Chinese Medicine on Chemotherapy-Induced Myelosuppression and Febrile Neutropenia in Breast Cancer Patients

Title. Chemotherapy-induced myelosuppression lowers the quality of life in breast cancer patients and causes many complications. Traditional Chinese Medicine (TCM) is a widely used complementary and alternative medicine therapies. Objective. To study whether TCM can reduce the incidence of chemotherapy-induced leukopenia, neutropenia, and febrile neutropenia (FN) in breast cancer patients. Methods. The data were analyzed retrospectively between patients who received TCM treatment (group 1, n=453) and patients who did not receive TCM treatment (group 2, n=359). Significant risk factors associated with the occurrence of chemotherapy-induced leukopenia, neutropenia, and FN were identified using multivariate analysis. Propensity score-matched patients were analyzed to adjust for any baseline differences. Results. Group 1 patients had a significantly lower rate of chemotherapy-induced severe leukopenia, neutropenia, and FN, compared with group 2 (43% versus 71%, P<0.0001, 72% versus 78%, P=0.005, 6% versus 24%, P<0.0001, resp.). Multivariate analysis revealed that chemotherapy regimens containing anthracyclines combined with paclitaxel or docetaxel were the most significant predictor. Subgroup analysis indicated that TCM treatment showed benefit in relieving chemotherapy-induced leukopenia and FN in most chemotherapy regimens. Conclusions. TCM treatment could lower the risk of severe chemotherapy-induced leukopenia, neutropenia, and FN in breast cancer patients

HNF4α ubiquitination mediated by Peli1 impairs FAO and accelerates pressure overload-induced myocardial hypertrophy

Abstract Impaired fatty acid oxidation (FAO) is a prominent feature of metabolic remodeling observed in pathological myocardial hypertrophy. Hepatocyte nuclear factor 4alpha (HNF4α) is closely associated with FAO in both cellular processes and disease conditions. Pellino 1 (Peli1), an E3 ligase containing a RING-like domain, plays a crucial role in catalyzing polyubiquitination of various substrates. In this study, we aimed to investigate the involvement of HNF4α and its ubiquitination, facilitated by Peli1, in FAO during pressure overload-induced cardiac hypertrophy. Peli1 systemic knockout mice (Peli1KO) display improved myocardial hypertrophy and cardiac function following transverse aortic constriction (TAC). RNA-seq analysis revealed that changes in gene expression related to lipid metabolism caused by TAC were reversed in Peli1KO mice. Importantly, both HNF4α and its downstream genes involved in FAO showed a significant increase in Peli1KO mice. We further used the antagonist BI6015 to inhibit HNF4α and delivered rAAV9-HNF4α to elevate myocardial HNF4α level, and confirmed that HNF4α inhibits the development of cardiac hypertrophy after TAC and is essential for the enhancement of FAO mediated by Peli1 knockout. In vitro experiments using BODIPY incorporation and FAO stress assay demonstrated that HNF4α enhances FAO in cardiomyocytes stimulated with angiotension II (Ang II), while Peli1 suppresses the effect of HNF4α. Mechanistically, immunoprecipitation and mass spectrometry analyses confirmed that Peli1 binds to HNF4α via its RING-like domain and promotes HNF4α ubiquitination at residues K307 and K309. These findings shed light on the underlying mechanisms contributing to impaired FAO and offer valuable insights into a promising therapeutic strategy for addressing pathological cardiac hypertrophy