KLF transcription factors in bone diseases.

Krüppel-like factors (KLFs) are crucial in the development of bone disease. They are a family of zinc finger transcription factors that are unusual in containing three highly conserved zinc finger structural domains interacting with DNA. It has been discovered that it engages in various cell functions, including proliferation, apoptosis, autophagy, stemness, invasion and migration, and is crucial for the development of human tissues. In recent years, the role of KLFs in bone physiology and pathology has received adequate attention. In addition to regulating the normal growth and development of the musculoskeletal system, KLFs participate in the pathological process of the bones and joints and are intimately linked to several skeletal illnesses, such as osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP) and osteosarcoma (OS). Consequently, targeting KLFs has emerged as a promising therapeutic approach for an array of bone disorders. In this review, we summarize the current literature on the importance of KLFs in the emergence and regulation of bone illnesses, with a particular emphasis on the pertinent mechanisms by which KLFs regulate skeletal diseases. We also discuss the need for KLFs-based medication-targeted treatment. These endeavours offer new perspectives on the use of KLFs in bone disorders and provide prognostic biomarkers, therapeutic targets and possible drug candidates for bone diseases.

Potential Targets of Natural Products for Improving Cardiac Ischemic Injury: The Role of Nrf2 Signaling Transduction.

Myocardial ischemia is the leading cause of health loss from cardiovascular disease worldwide. Myocardial ischemia and hypoxia during exercise trigger the risk of sudden exercise death which, in severe cases, will further lead to myocardial infarction. The Nrf2 transcription factor is an important antioxidant regulator that is extensively engaged in biological processes such as oxidative stress, inflammatory response, apoptosis, and mitochondrial malfunction. It has a significant role in the prevention and treatment of several cardiovascular illnesses, since it can control not only the expression of several antioxidant genes, but also the target genes of associated pathological processes. Therefore, targeting Nrf2 will have great potential in the treatment of myocardial ischemic injury. Natural products are widely used to treat myocardial ischemic diseases because of their few side effects. A large number of studies have shown that the Nrf2 transcription factor can be used as an important way for natural products to alleviate myocardial ischemia. However, the specific role and related mechanism of Nrf2 in mediating natural products in the treatment of myocardial ischemia is still unclear. Therefore, this review combs the key role and possible mechanism of Nrf2 in myocardial ischemic injury, and emphatically summarizes the significant role of natural products in treating myocardial ischemic symptoms, thus providing a broad foundation for clinical transformation.

Phytochemicals against Osteoarthritis by Inhibiting Apoptosis.

Osteoarthritis (OA) is a chronic joint disease that causes pathological changes in articular cartilage, synovial membrane, or subchondral bone. Conventional treatments for OA include surgical and non-surgical methods. Surgical treatment is suitable for patients in the terminal stage of OA. It is often the last choice because of the associated risks and high cost. Medication of OA mainly includes non-steroidal anti-inflammatory drugs, analgesics, hyaluronic acid, and cortico-steroid anti-inflammatory drugs. However, these drugs often have severe side effects and cannot meet the needs of patients. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Apoptosis is programmed cell death, which is a kind of physiologic cell suicide determined by heredity and conserved by evolution. Inhibition of apoptosis-related pathways has been found to prevent and treat a variety of diseases. Excessive apoptosis can destroy cartilage homeostasis and aggravate the pathological process of OA. Therefore, inhibition of apoptosis-related factors or signaling pathways has become an effective means to treat OA. Phytochemicals are active ingredients from plants, and it has been found that phytochemicals can play an important role in the prevention and treatment of OA by inhibiting apoptosis. We summarize preclinical and clinical studies of phytochemicals for the treatment of OA by inhibiting apoptosis. The results show that phytochemicals can treat OA by targeting apoptosis-related pathways. On the basis of improving some phytochemicals with low bioavailability, poor water solubility, and high toxicity by nanotechnology-based drug delivery systems, and at the same time undergoing strict clinical and pharmacological tests, phytochemicals can be used as a potential therapeutic drug for OA and may be applied in clinical settings.

Regulation and therapy, the role of JAK2/STAT3 signaling pathway in OA: a systematic review.

Osteoarthritis (OA) is a multifactorial chronic disease primarily characterized by the degeneration of articular cartilage. Currently, there is a lack of effective treatments for OA other than surgery. The exploration of the mechanisms of occurrence is important in exploring other new and effective treatments for OA. The current evidence shows that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays a vital role in cytogenesis and is involved in OA progression. The terms "JAK2", "STAT3", and "Osteoarthritis"were used in a comprehensive literature search in PubMed to further investigate the relationship between the JAK2/STAT3 signaling pathway and OA. This review focuses on the role and mechanism of JAK2/STAT3 signaling in cartilage degradation, subchondral bone dysfunction, and synovial inflammation. In addition, this review summarizes recent evidence of therapeutic approaches to treat OA by targeting the JAK2/STAT3 pathway to accelerate the translation of evidence into the progression of strategies for OA treatment. Video abstract.

Two-dimensional memristive hyperchaotic maps with different coupling frames and its hardware implementation.

Continuous-time memristors have been used in numerous chaotic circuit systems. Similarly, the discrete memristor model applied to a discrete map is also worthy of further study. To this end, this paper first proposes a discrete memristor model and analyzes the voltage-current characteristics of the memristor. Also, the discrete memristor is coupled with a one-dimensional (1D) sine chaotic map through different coupling frameworks, and two different two-dimensional (2D) chaotic map models are generated. Due to the presence of linear fixed points, the stability of the 2D memristor-coupled chaotic map depends on the choice of control parameters and initial states. The dynamic behavior of the chaotic map under different coupled map frameworks is investigated by using various analytical methods, and the results show that different coupling frameworks can produce different complex dynamical behaviors for memristor chaotic maps. The dynamic behavior based on parameter control is also investigated. The numerical experimental results show that the change of parameters can not only enrich the dynamic behavior of a chaotic map, but also increase the complexity of the memristor-coupled sine map. In addition, a simple encryption algorithm is designed based on the memristor chaotic map under the new coupling framework, and the performance analysis shows that the algorithm has a strong ability of image encryption. Finally, the numerical results are verified by hardware experiments.

Comparison of buttress plate and cannulated screw in the treatment of anteromedial coronoid fracture with elbow posteromedial rotatory instability.

PURPOSE: The purpose of this study is to compare the effect of buttress plate and cannulated screw in the treatment of anteromedial coronoid fracture with posteromedial rotatory instability (PMRI). METHODS: We retrospectively evaluated patients who were diagnosed with O'Driscoll type 2 fractures combined with elbow posteromedial rotatory instability and underwent surgery for anteromedial coronoid fracture between August 2014 and March 2019. They were divided into buttress plate (n=16) and cannulated screw (n=11) groups. The elbow range of motion, visual analog scale (VAS), Mayo elbow performance score (MEPS), and disabilities of the arm, shoulder, and hand score (DASH) were used for clinical outcome assessment. RESULT: There were no significant differences in clinical outcomes. However, the surgical time was significantly shorter in cannulated screw group (85.45±4.156) compared to the buttress plate group (93.81±8.863, P=0.008), and the surgical time was associated with internal fixation (P=0.008). CONCLUSION: Although there was selection of cases in that small fragments were treated with buttress plate and large fragments with cannulated screw, the buttress plate and cannulated screw have comparable functional outcomes on fixation of the anteromedial coronoid fracture with elbow PMRI. The fixation of the anteromedial coronoid fracture with large fragments using the cannulated screw has a shorter operation time.

Conservative versus surgical management of isolated O'Driscoll II coronoid fracture: A systematic review.

PURPOSE: The purpose of this systematic review is to summarize the current literature on conservative and surgical management of isolated O'Driscoll II coronoid fracture. STUDY DESIGN: Systematic review. METHODS: We systematically searched Medline, Embase, Google Scholar, and Web of Science databases for published studies by complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and using the keywords "isolated coronoid fracture," "O'Driscoll type 2 coronoid fracture," "anteromedial coronoid fracture," "anteromedial facet coronoid fracture," "posteromedial rotatory instability," and "varus posteromedial rotatory instability." Patients were divided into conservative treatment and surgical treatment groups. Oxford Centre for Evidence-Based Medicine and Methodological Index for Non-Randomized Studies were assessed to determine each article's quality. The primary outcomes of the present reviews were the Mayo elbow performance score (MEPS) and the disabilities of the arm, shoulder, and hand (DASH) score, and the secondary outcomes were associated with complications and reoperations. Eligible trials were independently chosen by two review authors, and a third reviewer resolved all disagreements. RESULTS: The search yielded 458 records, among which 446 articles were of relevance, and 12 were included. In the final review, 138 patients were evaluated-98 (71%) who received surgical treatment and 40 (29%) who received conservative treatment. The mean MEPS score and the DASH score of surgical treatment were 91 and 8, respectively; 69.8% of patients had excellent scores, and 27.0% had good scores. The mean MEPS score and the DASH score of conservative treatment were 92 and 12, respectively; 70.6% of patients had excellent scores, and 23.5% had good scores. CONCLUSIONS: In select cases, conservative treatment can achieve good results in the treatment of isolated O'Driscoll II coronoid fracture when a stricter indication is followed. However, there is insufficient evidence to recommend the appropriate treatment for a particular fracture subtype, and there is a need for more high-quality randomized controlled trials to determine which treatment is superior.

Open-Framework Iron Fluoride Phosphates Based on Chain, Trinuclear, and Tetranuclear Chain FeIII Building Units: Crystal Structures and Magnetic Properties.

We report the synthesis and characterization of a series of new open-framework iron fluoride-fluorophosphates based on linear, trinuclear, and tetranuclear chain FeIII building units. KFe2(PO3F)2F3 (I) consists of {Fe2(O3F)2F2}10- zigzag chains interconnected by P(O/F)4 tetrahedra forming a three-dimensional (3D) open framework. K2Fe(PO2.5F1.5)2F2 (II) is built up by {Fe(PO2.5F1.5)2F2}2- chains separated by K+ cation layers. The framework for K3Fe3(PO4)(PO3F)2F5 (III) contains two-dimensional {Fe3O4F4(PO3F)2}2- sheets, which are built from trimeric Fe-octahedra insulated by PO3F tetrahedra. The macroanionic framework of K3Fe4(PO4)2F9 (IV) comprises linear {Fe4O8F9}10- chains consisting of tetranuclear magnetic clusters of [Fe4O8F9]10- formed via corner-sharing fluorine atoms decorated with PO4 groups. The magnetic characterization of three iron fluorophosphates reveals diversified magnetism: S = 5/2 spin chains for I, antiferromagnetically coupled triangular Fe units for III, and coupled tetrahedral S = 5/2 spin chains for IV. IV shows strong geometric frustration thanks to its spin motifs of corner-shared tetrahedral clusters.

Effects of low-intensity pulsed ultrasound on knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To systemically review the effects of low-intensity pulsed ultrasound (LIPUS) on pain relief and functional recovery in patients with knee osteoarthritis (KOA). DATA SOURCES: PubMed, Web of Science, Cochrane Library, Physiotherapy Evidence Database (PEDro), and China National Knowledge Infrastructure (CNKI) were used from inception to 18 March 2022. REVIEW METHODS: Meta-analysis was performed to evaluate pain and function recovery between control and LIPUS groups. Standardized mean difference (SMD) or mean difference (MD) and 95% confidence interval (CI) were calculated, and data were combined using the fixed or random-effect model. RESULTS: Thirteen studies involving 807 patients with KOA were included. Patients' outcomes treated by LIPUS were improved significantly, including Visual analog scale (VAS) score (MD = -0.95, 95% CI: -1.43 to -0.48，P < 0.001), Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score (MD = -4.35, 95% CI: -8.30 to -0.40, P = 0.0309), Lysholm score (SMD = 1.59, 95% CI: 1.29 to 1.90, P < 0.001), Lequesne index (MD = -1.33, 95% CI: -1.69 to -0.96, P < 0.001), Range of motion (ROM) (MD = 2.43, 95% CI: 0.39 to 4.46, P = 0.0197) and 50 meter walking time (SMD = 1.48, 95% CI: 0.46 to 2.49, P = 0.0044). Subgroup analyses showed monotherapy of LIPUS produced a better effect on reducing VAS score (P = 0.0213), and the shorter therapeutic period (≤4 weeks) produced a more significant effect on raising the WOMAC score (P = 0.0083). CONCLUSION: LIPUS was beneficial for pain relief and functional knee recovery and maybe as an alternative therapy in KOA rehabilitation.

Expeditious, scalable solution growth of metal oxide films by combustion blade coating for flexible electronics.

Metal oxide (MO) semiconductor thin films prepared from solution typically require multiple hours of thermal annealing to achieve optimal lattice densification, efficient charge transport, and stable device operation, presenting a major barrier to roll-to-roll manufacturing. Here, we report a highly efficient, cofuel-assisted scalable combustion blade-coating (CBC) process for MO film growth, which involves introducing both a fluorinated fuel and a preannealing step to remove deleterious organic contaminants and promote complete combustion. Ultrafast reaction and metal-oxygen-metal (M-O-M) lattice condensation then occur within 10-60 s at 200-350 °C for representative MO semiconductor [indium oxide (In2O3), indium-zinc oxide (IZO), indium-gallium-zinc oxide (IGZO)] and dielectric [aluminum oxide (Al2O3)] films. Thus, wafer-scale CBC fabrication of IGZO-Al2O3 thin-film transistors (TFTs) (60-s annealing) with field-effect mobilities as high as ∼25 cm2 V-1 s-1 and negligible threshold voltage deterioration in a demanding 4,000-s bias stress test are realized. Combined with polymer dielectrics, the CBC-derived IGZO TFTs on polyimide substrates exhibit high flexibility when bent to a 3-mm radius, with performance bending stability over 1,000 cycles.

Inference of Molecular Regulatory Systems Using Statistical Path-Consistency Algorithm.

One of the key challenges in systems biology and molecular sciences is how to infer regulatory relationships between genes and proteins using high-throughout omics datasets. Although a wide range of methods have been designed to reverse engineer the regulatory networks, recent studies show that the inferred network may depend on the variable order in the dataset. In this work, we develop a new algorithm, called the statistical path-consistency algorithm (SPCA), to solve the problem of the dependence of variable order. This method generates a number of different variable orders using random samples, and then infers a network by using the path-consistent algorithm based on each variable order. We propose measures to determine the edge weights using the corresponding edge weights in the inferred networks, and choose the edges with the largest weights as the putative regulations between genes or proteins. The developed method is rigorously assessed by the six benchmark networks in DREAM challenges, the mitogen-activated protein (MAP) kinase pathway, and a cancer-specific gene regulatory network. The inferred networks are compared with those obtained by using two up-to-date inference methods. The accuracy of the inferred networks shows that the developed method is effective for discovering molecular regulatory systems.

A New Fault Diagnosis of Rolling Bearing Based on Markov Transition Field and CNN.

The rolling bearing is a crucial component of the rotating machine, and it is particularly vital to ensure its normal operation. In addition, the selection of different category features will add uncertainty and bias to the classification results. In order to decrease the interference of these factors to fault diagnosis, a new method that automatically learns the features of the data combined with Markov transition field (MTF) and convolutional neural network (CNN) is proposed in this paper, namely MTF-CNN. The MTF contributes to convert the original time series into corresponding figures, and the CNN is used to extract the deep feature information in the figure to complete the fault diagnosis. The effectiveness of the proposed method is verified by two public data sets. The experimental results show that MTF-CNN can classify different types of faults, and the highest accuracy rate can reach 100%. Likewise, the classification accuracy of this method is higher than some existing methods.

Cycloidal Magnetic Order Promoted by Labile Mixed Anionic Paths in M2(SeO3)F2 (M = Mn2+, Ni2+).

Two M2(SeO3)F2 fluoro-selenites (M = Mn2+, Ni2+) have been synthesized using optimized hydrothermal reactions. Their 3D framework consists of 1D-[MO2F2]4-chains of edge-sharing octahedra with a rare topology of alternating O-O and F-F µ2 bridges. The interchain corner-sharing connections are assisted by the mixed O vs F anionic nature and develop a complex set of M-X-M superexchanges as calculated by LDA+U. Their interplay induces prominent in-chain antiferromagnetic frustration, while the interchain exchanges are responsible for the cycloidal magnetic structure observed below TN ≈ 21.5 K in the Ni2+ case. For comparison the Mn2+ compound develops a nearly collinear spin (canted) ordering below TN ≈ 26 K with ferromagnetic chain units.

Variable Structures and One-Dimensional-Canting Antiferromagetism Found in Fluoride Selenates, A2Mn(SeO4)F3 (A = K, Rb, Cs).

Three new alkali-metal manganese fluoride selenates, A2Mn(SeO4)F3 (A = K, Rb, Cs), were prepared through hydrothermal redox reactions. The products consisted of one-dimensional polymeric anionic ∞[Mn(SeO4)F3]2- chains, where the A+ cations are connected by O and/or F atoms to form blocks with two-dimensional layers. A2Mn(SeO4)F3 (A= Rb, Cs) is isostructural with the monoclinic space group P21/c, while K2Mn(SeO4)F3 crystallizes in the orthorhombic space group Pbcn. A2Mn(SeO4)F3 (A = K, Rb, Cs) forms spin chains of Mn3+ with different Mn-F-Mn bridges, which showed canting antiferromagnetic behaviors. Single-crystal magnetic measurements revealed that the magnetic moments of the Mn ions were more canted for larger alkali-metal compounds in an antiferromagnetically ordered state.

New global dynamical results and application of several SVEIS epidemic models with temporary immunity.

This work applies a novel geometric criterion for global stability of nonlinear autonomous differential equations generalized by Lu and Lu (2017) to establish global threshold dynamics for several SVEIS epidemic models with temporary immunity, incorporating saturated incidence and nonmonotone incidence with psychological effect, and an SVEIS model with saturated incidence and partial temporary immunity. Incidentally, global stability for the SVEIS models with saturated incidence in Cai and Li (2009), Sahu and Dhar (2012) is completely solved. Furthermore, employing the DEDiscover simulation tool, the parameters in Sahu and Dhar'model are estimated with the 2009-2010 pandemic H1N1 case data in Hong Kong China, and it is validated that the vaccination programme indeed avoided subsequent potential outbreak waves of the pandemic. Finally, global sensitivity analysis reveals that multiple control measures should be utilized jointly to cut down the peak of the waves dramatically and delay the arrival of the second wave, thereinto timely vaccination is particularly effective.

Aggregation control in natural brush-printed conjugated polymer films and implications for enhancing charge transport.

Shear-printing is a promising processing technique in organic electronics for microstructure/charge transport modification and large-area film fabrication. Nevertheless, the mechanism by which shear-printing can enhance charge transport is not well-understood. In this study, a printing method using natural brushes is adopted as an informative tool to realize direct aggregation control of conjugated polymers and to investigate the interplay between printing parameters, macromolecule backbone alignment and aggregation, and charge transport anisotropy in a conjugated polymer series differing in architecture and electronic structure. This series includes (i) semicrystalline hole-transporting P3HT, (ii) semicrystalline electron-transporting N2200, (iii) low-crystallinity hole-transporting PBDTT-FTTE, and (iv) low-crystallinity conducting PEDOT:PSS. The (semi-)conducting films are characterized by a battery of morphology and microstructure analysis techniques and by charge transport measurements. We report that remarkably enhanced mobilities/conductivities, as high as 5.7×/3.9×, are achieved by controlled growth of nanofibril aggregates and by backbone alignment, with the adjusted R2 (R2adj) correlation between aggregation and charge transport as high as 95%. However, while shear-induced aggregation is important for enhancing charge transport, backbone alignment alone does not guarantee charge transport anisotropy. The correlations between efficient charge transport and aggregation are clearly shown, while mobility and degree of orientation are not always well-correlated. These observations provide insights into macroscopic charge transport mechanisms in conjugated polymers and suggest guidelines for optimization.

A novel 3D non-autonomous system with parametrically excited abundant dynamics and bursting oscillations.

In this paper, a novel non-autonomous chaotic system with rich dynamical behaviors is proposed by introducing parametric excitation to a Lorenz-like system, and the effect of the initial value of the excitation system on the resulting system dynamics is then thoroughly investigated. The attractors resulting from the proposed chaotic system will enter different oscillating states or have topological change when the initial value varies. Furthermore, some novel bursting oscillations and bifurcation mechanism are revealed. Stability and bifurcation of the proposed 3D non-autonomous system are comprehensively investigated to analyze the causes of the observed dynamics through a range of analytical methods, including bifurcation diagram, Lyapunov exponent spectrum, and sequence and phase diagrams. Software simulation and hardware experimentation are conducted in this study, which verify the dynamic behaviors of the proposed chaotic system. This study will create a new perspective and dimension of perceiving non-autonomous chaotic systems and exploring their applicability in real-world engineering applications.

Oxide-Polymer Heterojunction Diodes with a Nanoscopic Phase-Separated Insulating Layer.

Organic semiconductor-insulator blend films are widely explored for high-performance electronic devices enabled by unique phase-separation and self-assembly phenomena at key device interfaces. Here we report the first demonstration of high-performance hybrid diodes based on p- n junctions formed by a p-type poly(3-hexylthiophene) (P3HT)-poly(methyl methacrylate) (PMMA) blend and n-type indium-gallium-zinc oxide (IGZO). The thin film morphology, microstructure, and vertical phase-separation behavior of the P3HT films with varying contents of PMMA are systematically analyzed. Microstructural and charge transport evaluation indicates that the polymer insulator component positively impacts the morphology, molecular orientation, and effective conjugation length of the P3HT films, thereby enhancing the heterojunction performance. Furthermore, the data suggest that PMMA phase segregation creates a continuous nanoscopic interlayer between the P3HT and IGZO layers, playing an important role in enhancing diode performance. Thus, the diode based on an optimal P3HT-PMMA blend exhibits a remarkable 10-fold increase in forward current versus that of a neat P3HT diode, yielding an ideality factor value as low as 2.5, and a moderate effective barrier height with an excellent rectification ratio. These results offer a new approach to simplified manufacturing of low-cost, large-area hybrid inorganic-organic electronics technologies.

Studies of congenital cataract-related TSR1 mutation and its expression in the lens.

Congenital cataract (CC) is a rare disease with dysplasia of the lens, mainly characterized by partial or complete opacity of the lens. The molecular basis of the disease is complex, mutations in over 266 genes associated with congenital cataracts had been reported. In this study, a novel congenital cataract candidate gene TSR1 was identified by whole genome sequencing and Sanger sequencing in a Chinese congenital cataract family. The TSR1 c.202-1G>A substitution affected splicing of TSR1 mRNA was confirmed by a minigene assay. The expression of TSR1 in mouse lens, anterior lens capsule of age-related cataract patients and 24-week human fetal lens were determined by RT-PCR, Western blotting, and immunofluorescence assays. The expression of TSR1 in the embryonic and different developmental stages of the mouse lens was confirmed by analyzing the iSyTE database. The expression of TSR1 was down-regulated in the lens-specific CBP:p300 double knockout mouse, and a set of genes with the same expression pattern of Tsr1 in the CBP:p300 double knockout mouse lens were extracted for protein-protein interaction network analysis, and six proteins were screened for direct interaction with Tsr1. GO function analysis indicated that Tsr1 might play a role in the MAPK-Erk signaling pathway in addition to its involvement in ribosome assembly. This study provided valuable research clues to further clarify the function of Tsr1 in the lens.

Stochastic modelling of multistage carcinogenesis and progression of human lung cancer.

In this paper, we propose a stochastic multistage model that incorporates clonal expansion of premalignant cells and mutational events. Using the age-specific lung cancer as the test system, the proposed model is used to fit the incidence data in the Surveillance, Epidemiology, and End Results (SEER) registry. We first use the model with different numbers of mutations to fit the data of all lung cancer patients. Our results demonstrate that, although from two to six driver mutations in the genome of lung stem cells are reasonable for normal lung stem cells to become a malignant cell, three driver mutations are most likely to occur in the development of lung cancer. In addition, the models are employed to fit the data of female and male patients separately. The interesting result is that, for female patient data the best fit model contains four mutations while that for male patient data is the three-stage model. Finally, robustness analysis suggests that the decrease of cell net proliferation rates is more effective than the decrease of mutation rates in reducing the lung cancer risk.