Biofilm Formation, Motility, and Virulence of Listeria monocytogenes Are Reduced by Deletion of the Gene lmo0159, a Novel Listerial LPXTG Surface Protein.

Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen that causes listeriosis in humans and other animals. Surface proteins with the LPXTG motif have important roles in the virulence of L. monocytogenes. Lmo0159 is one such protein, but little is known about its role in L. monocytogenes virulence, motility, and biofilm formation. Here, we constructed and characterized a deletion mutant of lmo0159 (∆lmo0159). We analyzed not only the capacity of biofilm formation, motility, attachment, and intracellular growth in different cell types but also LD50; bacterial load in mice's liver, spleen, and brain; expression of virulence genes; and survival time of mice after challenge. The results showed that the cross-linking density of the biofilm of ∆lmo0159 strain was lower than that of WT by microscopic examination. The expression of biofilm-formation and virulence genes also decreased in the biofilm state. Subsequently, the growth and motility of ∆lmo0159 in the culture medium were enhanced. Conversely, the growth and motility of L. monocytogenes were attenuated by ∆lmo0159 at both the cellular and mouse levels. At the cellular level, ∆lmo0159 reduced plaque size; accelerated scratch healing; and attenuated the efficiency of adhesion, invasion, and intracellular proliferation in swine intestinal epithelial cells (SIEC), RAW264.7, mouse-brain microvascular endothelial cells (mBMEC), and human-brain microvascular endothelial cells (hCMEC/D3). The expression of virulence genes was also inhibited. At the mouse level, the LD50 of the ∆lmo0159 strain was 100.97 times higher than that of the WT strain. The bacterial load of the ∆lmo0159 strain in the liver and spleen was lower than that of the WT strain. In a mouse model of intraperitoneal infection, the deletion of the lmo0159 gene significantly prolonged the survival time of the mice, suggesting that the lmo0159 deletion mutant also exhibited reduced virulence. Thus, our study identified lmo0159 as a novel virulence factor among L. monocytogenes LPXTG proteins.

Effects of exogenous copper on microbial metabolic function and carbon use efficiency of Panax notoginseng planting soil.

Soil copper (Cu) pollution is a serious environmental risk in the Panax notoginseng planting area. However, the effect of Cu on soil microbial metabolism and nutrient cycling in this area remains unknown. Therefore, Biolog ECO-plate and enzyme stoichiometry methods were utilized in this study to investigate the impact of exogenous Cu (control: 0 mg·kg-1; Cu100: 100 mg·kg-1; Cu400: 400 mg·kg-1; and Cu600: 600 mg·kg-1) on the metabolic function of soil microbial and nutrient limitation in the P. notoginseng soil. The results indicated that Cu100 significantly increased soil organic carbon (SOC), total phosphorus (TP), soil C:N, microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) 9.89%, 15.65%, 17.91%, 61.87%, and 90.56% higher than the control, respectively. Moreover, the carbon source utilization ratio of carbohydrates, amino acids, and amphiphilic compounds of Cu100 also increased by 7.16%, 25.47%, and 84.68%, respectively, compared with the control. The activities of ß-1,4-glucosidase, cellobiohyrolase, leucine amino peptidase, ß-1,4-N-acetylglucosaminidase, and phosphatase significantly decreased with increasing Cu concentration. Soil enzyme stoichiometry showed that all treatments were limited by nitrogen (vector angle < 45°; 19.045-22.081). Cu600 led to the lowest carbon limitation (1.798) and highest carbon use efficiency (CUE:0.267). The PLS-SEM model also showed that MBC, MBN, MBP, and microbial diversity positively affected carbon and nitrogen limitation (0.654 and 0.424). Soil carbon, nitrogen, phosphorus, stoichiometric ratio, MBC, MBN, and MBP positively affected CUE (0.527 and 0.589). The microbial diversity index significantly negatively affected CUE (-1.490). Multiple linear stepwise regression analyses showed that CUE was mainly influenced by MBC, AP, C:P, and LAP. Thus, P. notoginseng soil can benefit soil microbial carbon and nitrogen limitations at low Cu concentrations. Clarifying the metabolic activity and nutritional status of microorganisms under Cu stress can provide some theoretical basis for realizing China's comprehensive and effective management and control policies for environmental risks from metals by 2035.

Eâ ¡B Mutation Reduces the Pathogenicity of Listeria monocytogenes by Negatively Regulating Biofilm Formation Ability, Infective Capacity, and Virulence Gene Expression.

To explore the role of the membrane permease ⅡB (EⅡB) gene of Listeria pathogenicity island 4 (LIPI-4) in the virulence of Listeria monocytogenes, both an EⅡB deletion strain (∆EⅡB) and a complemented strain were constructed. In vitro experiments demonstrated that EⅡB deletion affected the biofilm formation ability of the wild-type strain (Lm928). Moreover, this deletion decreased the intracellular proliferation abilities of L. monocytogenes. Mice infected with ∆EⅡB survived longer and experienced less weight loss on days 1, 2, and 3 post-infection. The bacterial load in the liver tissue of ∆EⅡB-infected mice was significantly reduced, and a considerable decrease in the blood levels of inflammatory cytokines IL-ß, IL-6, IL-10, and TNF-α were observed. Following EⅡB deletion, 65% (13/20) of genes were downregulated, 25% (5/20) were upregulated, and 10% (2/20) showed no change. These findings suggest that EⅡB deletion may reduce both the in vivo and in vitro virulence levels as well as the biofilm formation ability of Lm928 by downregulating the transcription levels of genes associated with virulence and biofilm formation. These findings provide a foundation for further examining the pathogenic mechanisms of LIPI-4 and EⅡB in L. monocytogenes.

ß-catenin mediates endodermal commitment of human ES cells via distinct transactivation functions.

BACKGROUND: ß-catenin, acting as the core effector of canonical Wnt signaling pathway, plays a pivotal role in controlling lineage commitment and the formation of definitive endoderm (DE) during early embryonic development. Despite extensive studies using various animal and cell models, the ß-catenin-centered regulatory mechanisms underlying DE formation remain incompletely understood, partly due to the rapid and complex cell fate transitions during early differentiation. RESULTS: In this study, we generated new CTNNB1-/- human ES cells (hESCs) using CRISPR-based insertional gene disruption approach and systematically rescued the DE defect in these cells by introducing various truncated or mutant forms of ß-catenin. Our analysis showed that a truncated ß-catenin lacking both N- and C-terminal domains (ΔN148C) could robustly rescue the DE formation, whereas hyperactive ß-catenin mutants with S33Y mutation or N-terminal deletion (ΔN90) had limited ability to induce DE lineage. Notably, the ΔN148C mutant exhibited significant nuclear translocation that was positively correlated with successful DE rescue. Transcriptomic analysis further uncovered that two weak ß-catenin mutants lacking the C-terminal transactivation domain (CTD) activated primitive streak (PS) genes, whereas the hyperactive ß-catenin mutants activated mesoderm genes. CONCLUSION: Our study uncovered an unconventional regulatory function of ß-catenin through weak transactivation, indicating that the levels of ß-catenin activity determine the lineage bifurcation from mesendoderm into endoderm and mesoderm.

Correlation of imaging characteristics of degenerative cervical myelopathy and the surgical approach with improvement for postoperative neck pain and neural function: a retrospective cohort study.

Background: Complex degenerative cervical spondylotic myelopathy (DCM) is characterized by a variety of complex imaging features. The surgical method for DCM remains controversial. This study aimed to examine the correlation between the imaging characteristics of DCM with varying degrees of complexity and the surgical approach and clinical outcome. Methods: A retrospective cohort study involving retrospective data collection was performed. A total of 139 patients with DCM who underwent surgery between January 2015 and January 2018 in the Orthopedics Department of Shanxi Bethune Hospital were divided into 3 groups according to the complexity of imaging features: 18 patients in the mild group, 66 patients in the moderate group, and 55 patients in the severe group. The Visual Analog Scale (VAS) and Japanese Orthopaedic Association (JOA) scores were used to compare the effects of neck pain and neural function prior to surgery according to the rate of improvement as of the last follow-up. Routine X-ray films were obtained at the follow-up of 3-6 months. The necessity of computed tomography (CT) and magnetic resonance imaging (MRI) examinations was determined based on clinical findings and X-ray images. Analysis of variance (ANOVA) was used to compare groups, the least significant difference (LSD) test was used for multiple comparisons, and the Chi-square test was used to compare classification indicators (imaging manifestations, gender), with P<0.05 being statistically significant. Binary logistic regression analysis was performed to determine the primary influencing factors of the JOA recovery rate. Results: In all three groups, JOA and VAS scores at the final follow-up were significantly higher than those before surgery (P<0.001). There were significant differences in the preoperative VAS and JOA scores between any two groups, as well as in the VAS and JOA scores and improvement rates at the last follow-up between the mild group and the moderate group and between the mild group and the severe group (P<0.001). Age, preoperative JOA scores, MRI intramedullary hyperintensity signal, and the degree of spinal cord compression were primarily related to the nervous system recovery rate (P<0.001). Conclusions: Age, MRI intramedullary hyperintensity signal, degree of spinal cord compression, and other variables were associated with the improvement of neural function in patients with DCM. Therefore, in addition to the JOA improvement rate or VAS score, additional factors, such as the patient's condition, the improvement in quality of life, and the patient's financial capacity, should be considered in evaluating the improvement of postoperative neck pain and neural function.

A Highly Stable Multifunctional Bi-Based MOF for Rapid Visual Detection of S2- and H2S Gas with High Proton Conductivity.

Metal organic frameworks (MOFs) constructed with bismuth metal have not been widely reported, especially multifunctional Bi-MOFs. Therefore, developing multifunctional MOFs is of great significance due to the increasing requirements of materials. In this work, a 3D Bi-MOF (Bi-TCPE) with multifunctionality was successfully constructed, demonstrating high thermal stability, water stability, a porous structure, and strong blue fluorescence emission. We evaluated the properties of Bi-TCPE in detecting anions (S2-, Cr2O72-, and CrO42-) in aqueous solution, along with the rapid visual detection of H2S gas and proton conduction. In terms of anion detection, Bi-TCPE achieved the rapid detection of trace S2- in aqueous solutions, while the Ksv value was 1.224 × 104 M-1 with a limit of detection (LOD) value of 1.93 µM through titration experiments. Furthermore, Bi-TCPE could sensitively detect Cr2O72- and CrO42-, with Ksv values of 1.144 × 104 and 1.066 × 104 M-1, respectively, while LOD reached 2.07 and 2.18 µM. Subsequently, we conducted H2S gas detection experiments, and the results indicated that Bi-TCPE could selectively detect H2S gas at extremely low concentrations (2.08 ppm) and with a fast response time (<10 s). We also observed significant color changes under both UV light and sunlight. Therefore, we developed a H2S detection test paper for the rapid visual detection of H2S gas. Finally, we evaluated the proton conductivity of Bi-TCPE, and the experimental results showed that the proton conductivity of Bi-TCPE reached 4.77 × 10-2 S·cm-1 at 98% RH and 90 °C, achieving an excellent value for unmodified and encapsulated MOFs. In addition, Bi-TCPE showed high stability in proton conduction experiments (it remained stable after 21 consecutive days of testing and 12 cycles of testing), demonstrating relatively high application value. These results indicate that Bi-TCPE is a multifunctional MOF material with great application potential.

Microenvironment-Responsive Targeted Nanomedicine for a Collaborative Integration of Tumor Theranostics and Bone Defect Repair.

Despite advancements in breast cancer treatment, bone metastases remain a significant concern for advanced breast cancer patients. Current theranostics strategies face challenges in integrating tumor theranostics and bone formation. Herein, this work develops an activatable targeted nanomedicine AuMnCO@BSA-N3 (AMCBN) to enable a novel collaborative integration of second near-infrared (NIR-II) fluorescence imaging guided precise theranostics for breast cancer bone metastases and osteogenic microenvironment remolding. This strategy employs a chemical coordination between noble metal complex and metal carbonyl (MnCO), with surface modification of azide groups to enhance tumor affinity through passive and active targeting. The initiated respondent behavior of AMCBN by tumor microenvironment accelerate the degradation of coordinated MnCO, resulting in a rapid release of multifunctional agents for efficient chemodynamic therapy (CDT)/gas synergistic therapy. Meanwhile, the exceptional bone-binding properties enable the efficient and controlled release of Mn2+ ions and carbon monoxide (CO) in the bone microenvironment, thereby facilitating the expression of osteogenesis-related proteins and establishing a novel synchronous theranostics process for tumor-bone repair.

Breathing Behavior and Superprotonic Conductivity of Two-Dimensional Flexible Metal-Organic Frameworks Tuned with Alkoxy Groups.

Flexible metal-organic frameworks (FMOFs) exhibit reversible structural transitions ("breathing" behaviors), which can regulate the proton transport passageway effectively. This property offers remarkable advantages for improving the proton conductivity. Our objective of this work is to design a single-variable flexibility synergistic strategy for the fabrication of FMOFs with high conductivity. Herein, four two-dimensional FMOFs, {[Co(4-bpdb)(R-ip)]·xsolvents}n (x = rich, 1-4), have been successfully designed and assembled (4-bpdb = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene and R-ip = MeO/EtO/n-PrO/n-BuO-isophthalate). Upon the release and/or absorption of different solvent molecules, they display reversible breathing behaviors, thereby resulting in the formation of the partial and complete solvent-free compounds {[Co(4-bpdb)(R-ip)]·ysolvents}n (y = free or poor, 1A-4A). This breathing behavior involves the synergistic self-adaption of the dynamic torsion of alkoxy groups and reversible structural transformation, leading to remarkable changes in cell parameters and void space, as evidenced by single-crystal X-ray diffraction, powder X-ray diffraction, and N2 and CO2 adsorption analyses. At 363 K and 98% relative humidity, 2A exhibits the best proton conductivity among the FMOFs. Its conductivity reaches 4.08 × 10-2 S cm-1 and is one of the highest conductivities shown by reported unmodified MOF-based proton conductors.

Bidirectional and Stepwise Rotation of Cells and Particles Using Induced Charge Electroosmosis Vortexes.

The rotation of cells is of significant importance in various applications including bioimaging, biophysical analysis and microsurgery. Current methods usually require complicated fabrication processes. Herein, we proposed an induced charged electroosmosis (ICEO) based on a chip manipulation method for rotating cells. Under an AC electric field, symmetric ICEO flow microvortexes formed above the electrode surface can be used to trap and rotate cells. We have discussed the impact of ICEO and dielectrophoresis (DEP) under the experimental conditions. The capabilities of our method have been tested by investigating the precise rotation of yeast cells and K562 cells in a controllable manner. By adjusting the position of cells, the rotation direction can be changed based on the asymmetric ICEO microvortexes via applying a gate voltage to the gate electrode. Additionally, by applying a pulsed signal instead of a continuous signal, we can also precisely and flexibly rotate cells in a stepwise way. Our ICEO-based rotational manipulation method is an easy to use, biocompatible and low-cost technique, allowing rotation regardless of optical, magnetic or acoustic properties of the sample.

[2 + 2] cycloaddition and its photomechanical effects on 1D coordination polymers with reversible amide bonds and coordination site regulation.

Photo-responsive materials can convert light energy into mechanical energy, with great application potential in biomedicine, flexible electronic devices, and bionic systems. We combined reversible amide bonds, coordination site regulation, and coordination polymer (CP) self-assembly to synthesize two 1D photo-responsive CPs. Obvious photomechanical behavior was observed under UV irradiation. By combining the CPs with PVA, the mechanical stresses were amplified and macroscopic driving behavior was realized. In addition, two cyclobutane amide derivatives and a pair of cyclobutane carboxyl isomers were isolated through coordination bond destruction and amide bond hydrolysis. Therefore, photo-actuators and supramolecular synthesis in smart materials may serve as important clues.

Bipolar Electrode-based Sheath-Less Focusing and Continuous Acoustic Sorting of Particles and Cells in an Integrated Microfluidic Device.

Sheath-less focusing and sorting of cells or particles is an important preprocessing step in a variety of biochemical applications. Most of the previous sorting methods depend on the use of sheath flows to realize efficient cell focusing. The sheath flow dilutes the sample and requires precise flow control via additional channels. We, for the first time, reported a method of bipolar electrode (BPE)-based sheath-less focusing, switching, and tilted-angle standing surface acoustic wave-based sorting of cells and particles in continuous flow. The device consists of a piezoelectric substrate with a pair of BPEs for focusing and switching, and a pair of interdigitated transducers for cell sorting. Smaller cells experience a weak acoustic force and reach the lower outlet, whereas larger cells are subjected to a strong acoustic force such that they are propelled toward the upper outlet. We first validate the device functionality by sorting 5 and 8 µm PS beads with a high sorting efficiency. The working and deflection regions were increased by propelling the particle beam toward the bottom edge of BPE via changing the applied voltage of BPE, further improving the sorting performance with high efficiency (94%) and purity (92%). We then conducted a verification for sorting THP-1 and yeast cells, and the efficiency and purity reached 90.7 and 91.5%, respectively. This integrated device eliminates the requirement of balancing the flow of several sheath inlets and provides a robust and unique approach for cell sorting applications, showing immense promise in various applications, such as medical diagnosis, drug delivery, and personalized medicine.

Three-dimensional rotation of deformable cells at a bipolar electrode array using a rotating electric field.

Three-dimensional rotation of cells is imperative in a variety of applications such as biology, medicine, and chemistry. We report for the first time a versatile approach for executing controllable 3D rotation of cells or particles at a bipolar electrode (BPE) array using a rotating electric field. The versatility of this method is demonstrated by 3D rotating various cells including yeast cells and K562 cells and the cells can be rotated to a desired orientation and immobilized for further operations. Our results demonstrate how electrorotation torque, induced charge electroosmosis (ICEO) flow and dielectrophoresis can be exerted on certain cells for modulating the rotation axis, speed, and direction. ICEO-based out-of-plane rotation is capable of rotating various cells in a vertical plane regardless of their shape and size. It can realize cell orientation by rotating cells toward a specific angle and enable cell rotation by steadily rotating multiple cells at a controllable speed. The rotation spectrum for in-plane rotation is further used to extract the cellular dielectric properties. This work offers a flexible method for controllable, contactless and precise rotation of different cells or particles, offering a rapid, high-throughput, and nondestructive rotation method for cell analysis and drug discovery.

An 18.3 MJ charging and discharging pulsed power supply system for the space plasma environment research facility (SPERF): the subsystem for the magnetic mirror coil.

The magnetic reconnection process relevant to that at the magnetotail is one of the research contents of the Space Plasma Environment Research Facility, which is under construction at the Harbin Institute of Technology in China. Two magnetic mirror sub-coils placed symmetrically in the vertical direction and connected in series cooperate with a dipole coil to generate a magnetic field environment similar to the Earth's magnetotail. A capacitor-based pulsed power supply (PPS) system with a modular design is developed to excite two magnetic mirror sub-coils to generate a magnetic field with a magnetic flux density of not less than 200 G at the center of the two sub-coils. The PPS should deliver a pulsed current with a peak of more than 8 kA, and the duration of the current not be less than 95% of the peak over 5 ms to two magnetic mirror sub-coils when the charging voltage is not less than 20 kV. In addition, the duration from the peak to 10% of the peak is not more than 130 ms. The detailed design of the PPS is discussed in this paper, and a test method is designed to reduce the risk of damage to the wires and the connection between the wires and the coaxial cables of the PPS when the PPS discharges at a higher charging voltage. Finally, the discharge test of the PPS is carried out to verify the design of the PPS.

Small extracellular vesicles derived from umbilical cord mesenchymal stem cells repair blood-spinal cord barrier disruption after spinal cord injury through down-regulation of Endothelin-1 in rats.

Spinal cord injury could cause irreversible neurological dysfunction by destroying the blood-spinal cord barrier (BSCB) and allowing blood cells like neutrophils and macrophages to infiltrate the spinal cord. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) found in the human umbilical cord have emerged as a potential therapeutic alternative to cell-based treatments. This study aimed to investigate the mechanism underlying the alterations in the BSCB permeability by human umbilical cord MSC-derived sEVs (hUC-MSCs-sEVs) after SCI. First, we used hUC-MSCs-sEVs to treat SCI rat models, demonstrating their ability to inhibit BSCB permeability damage, improve neurological repair, and reduce SCI-induced upregulation of prepro-endothelin-1 (prepro-ET-1) mRNA and endothelin-1 (ET-1) peptide expression. Subsequently, we confirmed that hUC-MSCs-sEVs could alleviate cell junction destruction and downregulate MMP-2 and MMP-9 expression after SCI, contributing to BSCB repair through ET-1 inhibition. Finally, we established an in vitro model of BSCB using human brain microvascular endothelial cells and verified that hUC-MSCs-sEVs could increase the expression of junction proteins in endothelial cells after oxygen-glucose deprivation by ET-1 downregulation. This study indicates that hUC-MSCs-sEVs could help maintain BSCB's structural integrity and promote functional recovery by suppressing ET-1 expression.

Label free and high-throughput discrimination of cells at a bipolar electrode array using the AC electrodynamics.

BACKGROUND: Cell characterization and manipulation play an important role in biological and medical applications. Cell viability evaluation is of significant importance for cell toxicology assay, dose test of anticancer drugs, and other biochemical stimulations. The electrical properties of cells change when cells transform from healthy to a pathological state. Current methods for evaluating cell viability usually requires a complicated chip and the throughput is limited. RESULTS: In this paper, a bipolar electrode (BPE) array based microfluidic device for assessing cell viability is exploited using AC electrodynamics. The viability of various cells including yeast cells and K562 cells, can be evaluated by analyzing the electro-rotation (ROT) speed and direction of cells, as well as the dielectrophoresis (DEP) responses of cells. Firstly, the cell viability can be identified by the position of the cell captured on the BPE electrode in terms of DEP force. Besides, cell viability can also be evaluated based on both the cell rotation speed and direction using ROT. Under the action of travelling wave dielectric electrophoresis force, the cell viability can also be distinguished by the rotational motion of cells on bipolar electrode edges. SIGNIFICANCE: This study demonstrates the utility of BPEs to enable scalable and high-throughput AC electrodynamics platforms by imparting a flexibility in chip design that is unparalleled by using traditional electrodes. By using BPEs, our proposed new technique owns wide application for cell characterization and viability assessment in situ detection and analysis.

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage.

Osteoarthritis (OA) is the most common degenerative bone and joint disease that can lead to disability and severely affect the quality of life of patients. However, its etiology and pathogenesis remain unclear. It is currently believed that articular cartilage lesions are an important marker of the onset and development of osteoarthritis. Long noncoding RNAs (lncRNAs) are a class of multifunctional regulatory RNAs that are involved in various physiological functions. There are many differentially expressed lncRNAs between osteoarthritic and normal cartilage tissues that play multiple roles in the pathogenesis of OA. Here, we reviewed lncRNAs that have been reported to play regulatory roles in the pathological changes associated with osteoarthritic cartilage and their potential as biomarkers and a therapeutic target in OA to further elucidate the pathogenesis of OA and provide insights for the diagnosis and treatment of OA.

Development and evaluation of nomograms for predicting osteoarthritis progression based on MRI cartilage parameters: data from the FNIH OA biomarkers Consortium.

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability worldwide. However, the existing methods for evaluating OA patients do not provide enough comprehensive information to make reliable predictions of OA progression. This retrospective study aimed to develop prediction nomograms based on MRI cartilage that can predict disease progression of OA. METHODS: A total of 600 subjects with mild-to-moderate osteoarthritis from the Foundation for National Institute of Health (FNIH) project of osteoarthritis initiative (OAI). The MRI cartilage parameters of the knee at baseline were measured, and the changes in cartilage parameters at 12- and 24-month follow-up were calculated. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to extract the valuable characteristic parameters at different time points including cartilage thickness, cartilage volume, subchondral bone exposure area and uniform cartilage thickness in different sub regions of the knee, and the MRI cartilage parameters score0, scoreΔ12, and scoreΔ24 at baseline, 12 months, and 24 months were constructed. ScoreΔ12, and scoreΔ24 represent changes between 12 M vs. baseline, and 24 M vs. baseline, respectively. Logistic regression analysis was used to construct the nomogram0, nomogramΔ12, and nomogramΔ24, including MRI-based score and risk factors. The area under curve (AUC) was used to evaluate the differentiation of nomograms in disease progression and subgroup analysis. The calibration curve and Hosmer-Lemeshow (H-L) test were used to verify the calibration of the nomograms. Clinical usefulness of each prediction nomogram was verified by decision curve analysis (DCA). The nomograms with predictive efficacy were analyzed by secondary analysis. Internal verification was assessed using bootstrapping validation. RESULTS: Each nomogram included cartilage score, KL grade, WOMAC pain score, WOMAC disability score, and minimum joint space width. The AUC of nomogram0, nomogramΔ12, and nomogramΔ24 in predicing the progression of radiology and pain were 0.69, 0.64, and 0.71, respectively. All three nomograms had good calibration. Analysis by DCA showed that the clinical effectiveness of nomogramΔ24 was higher than others. Secondary analysis showed that nomogram0 and nomogramΔ24 were more capable of predicting OA radiologic progression than pain progression. CONCLUSION: Nomograms based on MRI cartilage change were useful for predicting the progression of mild to moderate OA.

Comparison of the clinical efficacy of unilateral and bilateral pedicle screw short-segment fixation and fusion in the treatment of atlantoaxial fracture-dislocation.

BACKGROUND: Few studies have compared the clinical efficacy of unilateral and bilateral pedicle screw fixation and fusion in treating atlantoaxial fracture-dislocation. OBJECTIVE: To compare the efficacy of unilateral and bilateral fixation and fusion for atlantoaxial fracture-dislocation and to explore the feasibility of the unilateral surgical procedure. METHODS: Twenty-eight consecutive patients with atlantoaxial fracture-dislocation were included in the study from June 2013 to May 2018. They were divided into a unilateral fixation group and a bilateral fixation group (14 patients in each group with an average age of 43.6 ± 16.3 years and 51.8 ± 15.4 years, respectively). The unilateral group had a unilateral anatomical variation of the pedicle or vertebral artery, or traumatic pedicle destruction. All patients underwent atlantoaxial unilateral or bilateral pedicle screw fixation and fusion. Intraoperative blood loss and operation time were recorded. The visual analog scale (VAS) and Japanese Orthopedic Association (JOA) scoring systems were used to evaluate pre- and postoperative occipital-neck pain and neurological function. X-ray and computerized tomography (CT) were used to assess atlantoaxial stability, the implants' position, and bone graft fusion. RESULTS: All patients were followed up for 39-71 months postoperatively. Intraoperatively, no spinal cord or vertebral artery injury was observed. At the last follow-up, occipital-neck pain and neurological function in the two groups were significantly improved (P< 0.05). The X-ray films and CT showed satisfactory atlantoaxial stability, implant position, and osseous fusion in all the patients at 6 months postoperatively. CONCLUSION: Unilateral and bilateral pedicle screw fixation and fusion can restore atlantoaxial stability and improve occipital-neck pain and neurological function in patients with atlantoaxial fracture-dislocation. The unilateral surgical procedure can be a supplementary option for patients with unilateral abnormal atlantoaxial lesions.

Effect of biochar application rate on changes in soil labile organic carbon fractions and the association between bacterial community assembly and carbon metabolism with time.

Biochar aging affects the stability of soil carbon. Analyzing the effect of biochar on soil organic carbon (SOC) forms and their relations with microbial community assembly and carbon metabolism with time is helpful for soil carbon sequestration (by adapting the farm management approach). Four treatments with no, low, medium, and high biochar application rates (0 %, 1 %, 2 %, and 4 % of the total dry weight of topsoil before winter wheat planting, abbreviated as control, LB, MB, and HB, respectively) were conducted in the field. The SOC and particulate organic carbon positively correlated with the biochar application rate. Biochar decreased readily oxidizable carbon (P < 0.05) after 8 months of application compared to the control; however, the difference disappeared with time. Biochar increased dissolved organic carbon (DOC) but had no effect on water- soluble organic carbon (WSOC); DOC and WSOC decreased with time. Furthermore, LB and HB stabilized the bacterial alpha diversities with time. Based on high-throughput sequencing, HB reduced the relative abundance of Actinobacteriota but increased that of Acidobacteria (P < 0.05) after 12 months of biochar application. Time-wise, the bacterial community assembly was determined by deterministic processes that were significantly affected by the available nitrogen, DOC, or WSOC. Compared with the control, biochar decreased bacterial links and improved bacterial metabolism of phenolic acids and polymers with time, as evidenced by Biolog EcoPlates. Structural equation modeling revealed that the contribution of bacterial assembly processes to carbon metabolism changed with time. Microbial carbon metabolism was most positively influenced by differences in the composition of bacterial specialists. These findings reinforced that changes in soil labile organic carbon were time-dependent but not necessarilty affected by the biochar application rate.

The association between statin use and osteoarthritis-related outcomes: An updated systematic review and meta-analysis.

Objective: Findings among studies evaluating the effect of statin use and OA development in a 2020 meta-analysis of data from 11 observational studies of statin use and osteoarthritis (OA) revealed controversial results. We aimed to determine the associations between statin use and OA-related outcomes in an updated meta-analysis. Methods: The protocol was registered with PROSPERO (CRD42020163983). A systematic literature retrieval was performed in the online databases, including PubMed, Cochrane Library, Embase, Web of Science, and Scopus, from inception to 1 June 2022, for clinical studies that compared the effects of statin users vs. nonusers on OA-related outcomes risks. Systematic reviews and meta-analyses were performed to estimate the correlations between statin use and OA-related outcomes. Tendency analysis was also used to estimate dose-response effects. The risk of bias was evaluated with the Newcastle-Ottawa scale. Results: We included 23 studies involving more than 6,000,000 participants. Statin use was associated with increased OA risk (OR 1.099 [95%CI 1.002-1.206, p = 0.045]). Higher statin doses had higher OA risk (simvastatin equivalent daily of >40 mg). OA and related surgery risks were significantly reduced in statin users using antihypertensive drugs (AHDs). No significant differences were seen in other outcomes. Conclusion: This meta-analysis inferred that statin use might be associated with increased OA development, especially at higher doses. The present study highlights the importance of recognizing potential OA risk in the population with long-term and/or high-dose statin use, especially in older populations. In addition, AHDs are associated with lower OA risk and fewer surgeries in hypertensive statin users. Due to limitations of heterogeneity and confounders, more rigorous studies are needed to define the correlations between statin use and OA-related outcomes.