Marbofloxacin combined with heavy rare-earth ions makes better candidates for veterinary drugs: crystal structure and bio-activity studies.

Marbofloxacin (MB) is a newly developed fluoroquinolone antibiotic used especially as a veterinary drug. It may be regarded as the improved version of enrofloxacin owing to its antibacterial activity, enhanced bioavailability, and pharmacokinetic-pharmacodynamic (PK-PD) properties. In this study, nine heavy rare-earth ions (Y, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were selected in light of their potential antibacterial activity and satisfactory biosafety to afford the corresponding rare-earth metal complexes of MB: the MB-Ln series. Their chemical structures and coordination patterns were characterized using IR spectroscopy, HRMS, TGA, and X-ray single-crystal diffraction analysis. Our results confirmed that all the MB-Ln complexes yielded the coincident coordination modes with four MB ligands coordinating to the Ln(III) center. In vitro antibacterial screening on five typical bacteria strains revealed that the MB-Ln complexes exhibited antibacterial activities comparable with MB, as indicated by the MIC/MBC values, in which Escherichia coli and Salmonella typhi were the most sensitive ones to MB-Ln. Furthermore, the MB-Ln complexes were found to be much less toxic in vivo than MB, as suggested by the evaluated LD50 (50% lethal dose) values. All the MB-Ln series complexes fell in the LD50 range of 5000-15 000 mg kg-1, while the LD50 value of MB was only 1294 mg kg-1. Furthermore, MB-Lu, as the selected representative of MB-Ln, could effectively inhibit the activity of DNA gyrase, the same as MB, suggesting the primary antibacterial mechanism of the MB-Ln series. The results demonstrated the good prospects and potential of metal-based veterinary drugs with better drug performance.

Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer.

BACKGROUND: As an unconventional subpopulation of T lymphocytes, γδ T cells can recognize antigens independently of major histocompatibility complex restrictions. Recent studies have indicated that γδ T cells play contrasting roles in tumor microenvironments-promoting tumor progression in some cancers (eg, gallbladder and leukemia) while suppressing it in others (eg, lung and gastric). γδ T cells are mainly enriched in peripheral mucosal tissues. As the cervix is a mucosa-rich tissue, the role of γδ T cells in cervical cancer warrants further investigation. METHODS: We employed a multiomics strategy that integrated abundant data from single-cell and bulk transcriptome sequencing, whole exome sequencing, genotyping array, immunohistochemistry, and MRI. RESULTS: Heterogeneity was observed in the level of γδ T-cell infiltration in cervical cancer tissues, mainly associated with the tumor somatic mutational landscape. Definitely, γδ T cells play a beneficial role in the prognosis of patients with cervical cancer. First, γδ T cells exert direct cytotoxic effects in the tumor microenvironment of cervical cancer through the dynamic evolution of cellular states at both poles. Second, higher levels of γδ T-cell infiltration also shape the microenvironment of immune activation with cancer-suppressive properties. We found that these intricate features can be observed by MRI-based radiomics models to non-invasively assess γδ T-cell proportions in tumor tissues in patients. Importantly, patients with high infiltration levels of γδ T cells may be more amenable to immunotherapies including immune checkpoint inhibitors and autologous tumor-infiltrating lymphocyte therapies, than to chemoradiotherapy. CONCLUSIONS: γδ T cells play a beneficial role in antitumor immunity in cervical cancer. The abundance of γδ T cells in cervical cancerous tissue is associated with higher response rates to immunotherapy.

Multi-objective cooperative controller design for rapid state-of-charge balancing and flexible bus voltage regulation in shipboard DC microgrids.

In this paper, a multi-objective cooperative (MOC) controller based on average consensus algorithm is designed to achieve rapid State-of-Charge (SoC) balancing, proportional load current sharing, and flexible DC bus voltage regulation for parallel battery storage units (BSUs) in shipboard DC microgrids. Different from the conventional secondary controllers, the designed MOC controller can simultaneously achieve the above three control objectives with a fully distributed manner without requiring multiple controllers, thereby effectively improving the system stability and reducing the communication burden. Furthermore, an optimized convergence factor is designed to accelerate SoC balancing, and pinning control is introduced to obtain flexible and accurate DC bus voltage regulation. The process of SoC balancing and current sharing analysis, SoC convergence performance analysis, large-signal stability analysis, and global steady-state analysis verifies the rationality and stability of the MOC controller. Finally, the Matlab/Simulink simulation and StarSim HIL experimental results demonstrate the effectiveness and robustness of the designed MOC controller in a shipboard DC microgrid under various testing scenarios.

A novel artificial vertebral implant with Gyroid porous structures for reducing the subsidence and mechanical failure rate after vertebral body replacement.

BACKGROUND: Prosthesis subsidence and mechanical failure were considered significant threats after vertebral body replacement during the long-term follow-up. Therefore, improving and optimizing the structure of vertebral substitutes for exceptional performance has become a pivotal challenge in spinal reconstruction. METHODS: The study aimed to develop a novel artificial vertebral implant (AVI) with triply periodic minimal surface Gyroid porous structures to enhance the safety and stability of prostheses. The biomechanical performance of AVIs under different loading conditions was analyzed using the finite element method. These implants were fabricated using selective laser melting technology and evaluated through static compression and subsidence experiments. RESULTS: The results demonstrated that the peak stress in the Gyroid porous AVI was consistently lower than that in the traditional porous AVI under all loading conditions, with a maximum reduction of 73.4%. Additionally, it effectively reduced peak stress at the bone-implant interface of the vertebrae. Static compression experiments demonstrated that the Gyroid porous AVI was about 1.63 times to traditional porous AVI in terms of the maximum compression load, indicating that Gyroid porous AVI could meet the safety requirement. Furthermore, static subsidence experiments revealed that the subsidence tendency of Gyroid porous AVI in polyurethane foam (simulated cancellous bone) was approximately 15.7% lower than that of traditional porous AVI. CONCLUSIONS: The Gyroid porous AVI exhibited higher compressive strength and lower subsidence tendency than the strut-based traditional porous AVI, indicating it may be a promising substitute for spinal reconstruction.

Development and Performance Evaluation of Integrated Hybrid Power Module for Three-Phase Servo Motor Applications.

This study aims to develop a 30 kHz/12 kW silicon carbide (SiC)/Si integrated hybrid power module (iHPM) for variable frequency drive applications, particularly industrial servo motor control, and, additionally, to theoretically and experimentally assess its dynamic characteristics and efficiency during operation. This iHPM integrates a brake circuit, a three-phase Si rectifier, and a three-phase SiC inverter within a single package to achieve a minimal current path. A space-vector pulse width modulation (SVPWM) scheme is used to control the inverter power switches. In order to reduce parasitic inductance and power loss, an inductance cancellation design is implemented in the Si rectifier and SiC inverter. The switching transients and their parasitic effects during a three-phase operation are assessed through an electromagnetic-circuit co-simulation model, by which the power loss and efficiency of the iHPM are estimated. The modeled parasitic inductance of the inverter is validated through inductance measurement, and the effectiveness of the simulated results in terms of switching transients and efficiency is verified using the experimental results of the double pulse test and open-loop inverter operation, respectively. In addition, the power loss and efficiency of the SiC MOSFET inverter are experimentally compared against those of a commercial Si IGBT inverter.

The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. AIM OF THE STUDY: The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. METHODS: To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. RESULTS: Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. CONCLUSION: According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

Complete Low-Temperature Transformation and Dissolution of the Three Main Components in Corn Straw.

The conversion of biomass faces the challenge of mass and heat transfer, as well as the exertion of heterogeneous catalyst, because raw biomass exists usually in solid state. In this work, the simultaneous transformation and dissolution of the three main components (hemicellulose, cellulose, lignin) in corn straw were achieved in ethanol/ valerolactone (GVL)/H2 O (10 : 10 : 40, v/v/v) co-solvent system. With the assistance of AlCl3 ⋅ 6H2 O, the conversion of hemicellulose, lignin and cellulose was >96 % at 170 °C. The conversion of solid biomass into fluid, overcoming the mass transfer restrictions between solid biomass and solid catalysts, provides new raw materials to further upgrading. H2 O could penetrate inside the crystalline cellulose to swell even dissolve it, while ethanol and GVL acted as media to dissolve especially the G unit in lignin. The H+ derived from AlCl3 ⋅ 6H2 O hydrolysis could break the linkages of lignin-hemicellulose and glycosidic bond in saccharides, and aluminum chloride promoted the next degradation of polysaccharides to small molecules. Consequently, as high as 33.2 % yield of levulinic acid and 42.2 % yield of furfural were obtained. The cleavage of ß-O-4 and Cß -Cγ bonds in lignin produced large amounts of lignin-derived dimers and trimers. The total yield of monomeric phenols is up to 8 %.

The additional nitrogen atom breaks the uranyl structure: a combined photoelectron spectroscopy and theoretical study of NUO2.

We report a joint photoelectron spectroscopic and relativistic quantum chemistry study on gaseous NUO2-. The electron affinity (EA) of the neutral NUO2 molecule is reported for the first time with a value of 2.602(28) eV. The U-O and U-N stretching vibrational modes for the ground state and the first excited state are observed for NUO2. The geometric and electronic structures of both the anions and the corresponding neutrals are investigated by relativistic quantum chemistry calculations to interpret the photoelectron spectra and to provide insights into the nature of the chemical bonding. Both the ground state of the anion and neutral are calculated to be planar structures with C2v symmetry. Unlike the "T"-shape structure of UO3 which has a quasi-linear O-U-O angle, both the ground-state geometries of the anion and neutral have O-U-O bond angles of around 90°. The significant contraction of the O-U-O bond angle indicates the strong interaction between the U and N atoms compared with the "additional" oxygen in UO3. The chemical bonding calculation indicates that multiple bonding of U(VI) can occur in NUO2- and NUO2, and the UVI-N bond is significantly more covalent than the U-O bond. The current experimental and theoretical results reveal the difference between the U-N and U-O bond in the unified molecular system, and expand our understanding of the bonding capacities of actinide elements with the nitrogen atom.

Combinatorial Application of Papain and CD66B for Isolating Glioma- Associated Neutrophils.

BACKGROUND: Stromal cells in the tumor microenvironment play crucial roles in glioma development. Current methods for isolating tumor-associated stromal cells (such as neutrophils) are inefficient due to the conflict between tissue dissociation and cell surface protein protection, which hampers the research on patient-derived stromal cells. Our study aims to establish a novel method for isolating glioma-associated neutrophils (GANs). METHODS: To observe neutrophil-like polymorphonuclear cells, we performed Hematoxylin-Eosin staining on glioma tissues. For isolating single cells from glioma tissues, we evaluated the efficiency of tissue dissociation with FastPrep Grinder-mediated homogenization or proteases (trypsin or papain) digestion. To definite specific markers of GANs, fluorescence-activated cell sorting (FACS) and immunofluorescence staining were performed. FACS and Ficoll were performed for the separation of neutrophils from glioma tissue-derived single-cell or whole blood pool. To identify the isolated neutrophils, FACS and RT-PCR were carried out. RESULTS: Neutrophil-like cells were abundant in high-grade glioma tissues. Among the three tissue dissociation methods, papain digestion produced a 5.1-fold and 1.7-fold more living cells from glioma mass than physical trituration and trypsin digestion, respectively, and it preserved over 97% of neutrophil surface protein markers. CD66B could be adopted as a unique neutrophil surface protein marker for FACS sorting in glioma. Glioma-derived CD66B+ cells specifically expressed neutrophil marker genes. CONCLUSION: A combination of papain-mediated tissue dissociation and CD66B-mediated FACS sorting is an effective novel method for the isolation of GANs from glioma tissues.

Novel Three-Holed Titanium Plate Fixation during Open Door Laminoplasty for Cervical Spondylotic Myelopathy: Comparison with Conventional Titanium Plate.

OBJECTIVE: For reconstructing the posterior cervical muscular-ligament complex, attachment points and various modified techniques were designed and applied in clinical practice. This study investigated the clinical and radiographic outcomes of open door laminoplasty with modified centerpiece mini-plate fixation and extensor attachment point reconstruction in the treatment of cervical spondylotic myelopathy (CSM). METHODS: Sixty-nine patients with CSM who underwent C3-C7 open door laminoplasty at our hospital from January 2016 to May 2018 were divided into two groups: 37 and 32 patients underwent laminoplasty with modified and conventional centerpiece titanium plate fixation (MPF and CPF groups), respectively. Changes in cervical spinal angle (CSA), cervical range of motion (ROM), posterior cervical muscle atrophy, neurological function (Japanese Orthopaedic Association [JOA] score), Neck Disability Index (NDI), and axial symptom severity were compared between the two groups. RESULTS: There were no significant differences in operative duration (136.7 ± 23.9 vs 128.3 ± 21.5 min, t = 1.525, p > 0.05), volume of intraoperative blood loss (275.9 ± 33.1 vs 268.2 ± 31.6 ml, t = 0.984, p > 0.05), lamina open angle (41.2° ± 4.5° vs 39.4° ± 4.1°, t = 1.726, p > 0.05), and spinal cord drift distance (2.4 ± 0.3 vs 2.3 ± 0.4 mm, t = 1.184, p > 0.05) between the two groups. After surgery, JOA score significantly increased (p < 0.05), and neurological recovery rates were similar (62.7% vs 63.4%, t = 0.208, p > 0.05). The NDI score was significantly decreased in both the groups (p < 0.05); however, the MPF group recovered to a greater degree than the CPF group (8.3 ± 1.2 vs 9.8 ± 1.4) (t = 4.793, p < 0.05). There was no significant change in cervical ROM postoperatively compared with preoperatively in either group (p > 0.05). CSA decreased from 21.7° ± 2.8° to 18.3° ± 2.1°, and posterior cervical muscle cross-sectional area decreased from 35.2 ± 4.9 cm2 to 31.0 ± 4.1 cm2 in the CPF group (p < 0.05), but no significant change was observed in the MPF group (20.6° ± 2.5° to 20.4° ± 2.6°and 35.9 ± 5.1 to 34.1 ± 4.6 cm2 , respectively) (p > 0.05). Postoperative axial symptom severity was significantly worse in the CPF group than in the MPF group (Z = -2.357, p < 0.05). CONCLUSIONS: As an improvement to the conventional titanium plate, the modified centerpiece titanium plate effectively provides an attachment point for the posterior muscle-ligament complex, reducing posterior cervical muscle atrophy and improving neck function, without inflicting additional surgical trauma.

Research Progress on the Biological Activities of Metal Complexes Bearing Polycyclic Aromatic Hydrazones.

Due to the abundant and promising biological activities of aromatic hydrazones, it is of great significance to study the biological activities of their metal complexes for the research and development of metal-based drugs. In this review, we focus on the metal complexes of polycyclic aromatic hydrazones, which still do not receive much attention, and summarize the studies related to their biological activities. Although the large number of metal complexes in phenylhydrazone prevent them all from being summarized, the significant value of polycyclic aromatic hydrocarbons themselves (such as naphthalene and anthracene) as pharmacophores are also considered. Therefore, the bioactivities of the metal complexes of naphthylhydrazone and anthrahydrazone are focused on, and the recent research progress on the metal complexes of anthrahydrazone by the authors is also included. In terms of biological activities, these complexes mainly show antibacterial and anticancer activities, along with less bioactivities. The present review demonstrates that the structural design and bioactivities of these complexes are fundamental, which also indicates a certain structure-activity relationship (SAR) in some substructural areas. However, a systematic and comprehensive conclusion of the SAR is still not available, which suggests that more attention should be paid to the bioactivities of the metal complexes of polycyclic aromatic hydrazones since their potential in structural design and biological activity remains to be explored. We hope that this review will attract more researchers to devote their interest and energy into this promising area.

[Biomechanical evaluation of effects of percutaneous cement discoplasty and percutaneous cement interbody fusion on spinal stability].

Objective: To investigate the effects of percutaneous cement discoplasty (PCD) and percutaneous cement interbody fusion (PCIF) on spinal stability by in vitro biomechanical tests. Methods: Biomechanical test was divided into intact (INT) group, percutaneous lumbar discectomy (PLD) group, PCD group, and PCIF group. Six specimens of L 4, 5 (including vertebral bodies and intervertebral discs) from fresh male cadavers were taken to prepare PLD, PCD, and PCIF specimens, respectively. Before treatment and after the above treatments, the MTS multi-degree-of-freedom simulation test system was used to conduct the biomechanical test. The intervertebral height of the specimen was measured before and after the axial loading of 300 N, and the difference was calculated. The range of motion (ROM) and stiffness of the spine in flexion, extension, left/right bending, and left/right rotation under a torque of 7.5 Nm were calculated. Results: After axial loading, the change of intervertebral height in PLD group was more significant than that in other three groups ( P<0.05). Compared with INT group, the ROM in all directions significantly increased and the stiffness significantly decreased in PLD group ( P<0.05). Compared with INT group, the ROM of flexion, extension, and left/right rotation in PCD group significantly increased and the stiffness significantly decreased ( P<0.05); compared with PLD group, the ROM of flexion, extension, and left/right bending in PCD group significantly decreased and the stiffness significantly increased ( P<0.05). Compared with INT group, ROM of left/right bending in PCIF group significantly decreased and stiffness significantly increased ( P<0.05); compared with PLD group, the ROM in all directions significantly decreased and the stiffness significantly increased ( P<0.05); compared with PCD group, the ROM of flexion, left/right bending, and left/right rotation significantly decreased and stiffness significantly increased ( P<0.05). Conclusion: Both PCD and PCIF can provide good biomechanical stability. The former mainly affects the stiffness in flexion, extension, and bending, while the latter is more restrictive on lumbar ROM in all directions, especially in bending and rotation.

Energy Absorption Characteristics of Polygonal Bio-Inspired Honeycomb Column Thin-Walled Structure under Quasi-Static Uniaxial Compression Loading.

In this paper, we investigated the internal structure of the beetle elytra, i.e., two different structural forms I and II of the bio-inspired honeycomb column thin-walled structures (BHTS) that give the honeycomb sandwich structure frequently used in construction projects better mechanical properties and lightweight performance. BHTS specimens were fabricated by additive manufacturing selective laser melting (AM-SLM) using AlSi10Mg Al-Si alloy. In order to understand the effect of section angle number on BHTS during loading, quasi-static uniaxial compression tests were carried out and verified by numerical simulation. The experimental results showed that in the quasi-static uniaxial compression tests, the number of section angles greatly improved the energy absorption (EA) index of each BHTS: the average value of initial peak crushing force (PCF) of hexagonal BHTS increased by 108.82% and 43.44%, respectively, compared to triangular and rectangular BHTS. The average value of the mean crushing force (MCF) increased by 74.87% and 45.48%, respectively. The average value of EA increased by 89.02% and 46.64%, respectively. The results indicate that the number of section angles can be used as an effective way to enhance the EA of BHTS. This work can provide a reference for the design of high-efficiency energy absorbers and will be widely used in EA scenarios such as construction, transportation, etc.

Biomechanical Evaluation of Spinal Column after Percutaneous Cement Discoplasty: A Finite Element Analysis.

OBJECTIVE: To compare the biomechanical properties of percutaneous cement discoplasty (PCD) in the spinal column between different implant-endplate friction. METHODS: A validated L3-Scarumfinite element (FE) model was modified for simulation. In the PCD model, the L4/5 level was modified based on model 1 (M1) and model 2 (M2). In M1, the interaction between bone cement and endplate was defined as face-to-face contact with a friction coefficient of 0.3; in M2, the contact was defined as a Tie constraint. 7.5 N m moments of four physiological motions and axial load of 15, 100 and 400 N preload were imposed at the top of L3. The range of motion (ROM) and interface stress analysis of endplates, annulus fibrosus and bone cement of the operated level were calculated for comparisons among the three models. RESULTS: The ROM of M1 and M2 increased when compared with the intact model during flexion (FL) (17.5% vs 10.0%), extension (EX) (8.8% vs -8.8%), left bending (LB) (19.0% vs -17.2%) and left axial rotation (LR) (34.6% vs -3.8%). The stress of annulus fibrosus in M1 and M2 decreased in FL (-48.4% vs -57.5%), EX (-25.7% vs -14.7%), LB (-47.5% vs -52.4%), LR (-61.4% vs -68.7%) and axis loading of 100 N (-41.5% vs -15.3%), and 400 N (-27.9% vs -27.3%). The stress of upper endplate of M1 and M2 increased in FL (24.6% vs 24.7%), LB (82.2% vs 89.5%), LR (119% vs 62.4%) and axis loading of 100 N (64.6% vs 45.5%), and 400 N (58.2% vs 24.3%), but was similar in EX (2.9% vs 0.3%). The stress of lower endplate of M1 and M2 increased in FL (170.9% vs 175.0%), EX (180.8% vs 207.7%), LB (302.6% vs 274.7%), LR (332.4% vs 132.8%) and axis loading of 100 N (350.7% vs 168.6%), and 400 N (165.2% vs 106.7%). CONCLUSION: Percutaneous cement discoplasty procedure could make effect on the mobility or stiffness. The fusion of bone cement and endplate might have more biomechanical advantages, including of the decreasing rate of implant subsidence and dislocation, and the increase spine stability.

Tibio-Femoral Contact Force Distribution of Knee Before and After Total Knee Arthroplasty: Combined Finite Element and Gait Analysis.

OBJECTIVE: To assess the tibio-femoral contact forces before and after total knee arthroplasty (TKA) in patients with knee osteoarthritis (KOA) by three-dimensional (3D) finite element analysis (FEA) models and gait analysis. METHODS: Two hospitalized patients with Kellgren-Lawrence grade IV varus KOA and two healthy subjects were enrolled in this study. Both patients underwent unilateral TKA. FEA models were established based on CT and MR images of the knees of the patients with KOA and healthy subjects. Gait analysis was performed using a three-dimensional motion capture system with a force plate. Three direction forces at the ankle joints were calculated by inverse dynamic analysis, which provided the load for the FEA models. The total contact forces of the knee joints were also calculated by inverse dynamic analysis to enable comparisons with the results from the FEA models. The total knee contact forces, maximum von Mises stress, and stress distribution of the medial plateau were compared between the patients and healthy subjects. The distributions of the medial plateau force at 2 and 6 months postoperatively were compared with the distributions of the forces preoperatively and those in the healthy subjects. RESULTS: During static standing, the medial plateau bore the most of the total contact forces in the knees with varus KOA (90.78% for patient 1 and 93.53% for patient 2) compared with 64.75 ± 3.34% of the total force in the healthy knees. At the first and second peaks of the ground reaction force during the stance phase of a gait cycle, the medial plateau bore a much higher percentage of contact forces in patients with KOA (74.78% and 86.48%, respectively, for patient 1; 70.68% and 83.56%, respectively, for patient 2) than healthy subjects (61.06% ± 3.43% at the first peak and 72.09% ± 1.83% at the second peak). Two months after TKA, the percentages of contact forces on the medial tibial plateau were 79.65%-85.19% at the first and second peaks of ground reaction forces during the stance phase of a gait cycle, and the percentages decreased to 53.99% - 68.13% 6 months after TKA. CONCLUSION: FEA showed that TKA effectively restored the distribution of tibio-femoral contact forces during static standing and walking, especially 6 months after the surgery. The changes in the gait were consistent with the changes in the contact force distribution calculated by the FEA model.

Identification of Neural Progenitor Cell-associated Chemoradiotherapy Resistance Gene Set (ARL4C, MSN, TNFAIP6) for Prognosis of Glioma.

BACKGROUND: Glioma is the most common malignant intracranial tumor with high lethality. Despite surgery combined with chemoradiotherapy, the prognosis for patients with glioma remains poor. This is primarily due to acquired chemoradiotherapy resistance. Therefore, to improve the prognosis of glioma, further study into the mechanism of chemoradiotherapy resistance is needed. OBJECTIVE: This study aimed to (1) evaluate the prognosis of patients with glioma by using a prognostic risk score model constructed by chemoradiotherapy resistance genes, (2) provide new targets and directions for precise treatment of glioma, and (3) discuss the tumor heterogeneity of tumor cells. METHODS: According to therapy class and overall survival (OS), we identified 53 genes associated with glioma chemoradiotherapy resistance in The Cancer Genome Atlas Glioblastoma (TCGA GBM) database. Considering the important role of chemoradiotherapy resistance-related genes in the prognosis of glioma, we preliminarily screened and identified vital prognostic factors among these genes by using the Cox regression model of absolute contraction and selection operators in the TCGA GBM lower-grade glioma (TCGA GBMLGG) dataset. Next, the heterogeneity of the chemoradiotherapy resistance-associated genes in different glioma cells was revealed by single-cell sequencing in the GSE117891 cohort. RESULTS: A prognostic risk score model consisting of three genes (ARL4C, MSN, TNFAIP6) was constructed. The expression of this model was high in glioma neural progenitor cells (NPCs) and low in glioma oligodendrocytes. The OS rates were significantly lower in the high- vs. low-risk group. CONCLUSION: Our 3 gene risk score complements the current glioma diagnosis and provides a novel insight into chemoradiotherapy resistance mechanisms for the prognosis of patients with glioma.

The copper(II) complex of dantron showed therapeutic effect on bacterial gill-rot disease in tilapia infected by Flavobacterium columnar.

Dantron (DA), a kind of polyhydric anthraquinone and one of the bio-active ingredient in Rheum officinale was chosen as the ligand to coordinate with the bio-active copper(II) ion to achieve its antibacterial copper(II) complex, DA-Cu. The coordination structure of DA-Cu, both in the crystal state and solution state, was studied by spectroscopy and X-ray single-crystal diffraction analysis. The inhibition zone, MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) values regarding the in vitro antibacterial activity of DA-Cu towards Flavobacterium columnar, which causes the bacterial gill-rot disease on fish, were significant and specific. DA-Cu in vivo acute toxicity on zebrafish and tilapia was evaluated, suggesting that the higher dose of DA-Cu than 0.1 mg/mL might give potential toxicity. The further therapeutic effect of DA-Cu on the tested tilapia challenged by Flavobacterium columnar was also studied, which showed its clear advantage (including the survival rate, relative weight gain rate, and feed conversion ratio) over DA and the positive control, Sanhuang San, at a much lower dosage of 0.025 mg/mL.

Genetic and Functional Analyses of Archaeal ATP-Dependent RNA Ligase in C/D Box sRNA Circularization and Ribosomal RNA Processing.

RNA ligases play important roles in repairing and circularizing RNAs post-transcriptionally. In this study, we generated an allelic knockout of ATP-dependent RNA ligase (Rnl) in the hyperthermophilic archaeon Thermococcus kodakarensis to identify its biological targets. A comparative analysis of circular RNA reveals that the Rnl-knockout strain represses circularization of C/D box sRNAs without affecting the circularization of tRNA and rRNA processing intermediates. Recombinant archaeal Rnl could circularize C/D box sRNAs with a mutation in the conserved C/D box sequence element but not when the terminal stem structures were disrupted, suggesting that proximity of the two ends could be critical for intramolecular ligation. Furthermore, T. kodakarensis accumulates aberrant RNA fragments derived from ribosomal RNA in the absence of Rnl. These results suggest that Rnl is responsible for C/D box sRNA circularization and may also play a role in ribosomal RNA processing.

A New Calcium(II)-Based Substitute for Enrofloxacin with Improved Medicinal Potential.

Enrofloxacin (EFX) reacting with Ca(II) afforded a new complex, [Ca(EFX)2(H2O)4] (EFX-Ca), which was structurally characterized both in solid and solution chemistry. E. coli and S. typhi were tested to be the most sensitive strains for EFX-Ca. The LD50 value of EFX-Ca in mice was 7736 mg/kg, implying the coordination of EFX to Ca(II) effectively reduced its acute toxicity. EFX-Ca also decreased the plasma-binding rate and enhanced the drug distribution in rats along with longer elimination half-life. EFX-Ca also showed similar low in vivo acute toxicity and higher anti-inflammation induced by H2O2 or CuSO4 in zebrafish, with reactive oxygen species (ROS)-related elimination. The therapeutic effects of EFX-Ca on two types (AA and 817) of E. coli-infected broilers were also better than those of EFX, with cure rates of 78% and 88%, respectively. EFX-Ca showed promise as a bio-safe metal-based veterinary drug with good efficacy and lower toxicity.

Mixed Transcriptome Analysis Revealed the Possible Interaction Mechanisms between Zizania latifolia and Ustilago esculenta Inducing Jiaobai Stem-Gall Formation.

The smut fungus Ustilago esculenta infects Zizania latifolia and induces stem expansion to form a unique vegetable named Jiaobai. Although previous studies have demonstrated that hormonal control is essential for triggering stem swelling, the role of hormones synthesized by Z. latifolia and U. esculenta and the underlying molecular mechanism are not yet clear. To study the mechanism that triggers swollen stem formation, we analyzed the gene expression pattern of both interacting organisms during the initial trigger of culm gall formation, at which time the infective hyphae also propagated extensively and penetrated host stem cells. Transcriptional analysis indicated that abundant genes involving fungal pathogenicity and plant resistance were reprogrammed to maintain the subtle balance between the parasite and host. In addition, the expression of genes involved in auxin biosynthesis of U. esculenta obviously decreased during stem swelling, while a large number of genes related to the synthesis, metabolism and signal transduction of hormones of the host plant were stimulated and showed specific expression patterns, particularly, the expression of ZlYUCCA9 (a flavin monooxygenase, the key enzyme in indole-3-acetic acid (IAA) biosynthesis pathway) increased significantly. Simultaneously, the content of IAA increased significantly, while the contents of cytokinin and gibberellin showed the opposite trend. We speculated that auxin produced by the host plant, rather than the fungus, triggers stem swelling. Furthermore, from the differently expressed genes, two candidate Cys2-His2 (C2H2) zinc finger proteins, GME3058_g and GME5963_g, were identified from U. esculenta, which may conduct fungus growth and infection at the initial stage of stem-gall formation.