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Introduction A variety of hypoglycaemic drugs are used to treat polycystic ovarian syndrome (PCOS), but their efficacy remains insufficient. Glucokinase activators (GKAs) are a unique class of hypoglycaemic medications with emerging potential, notably in significantly reducing insulin resistance (IR). Nevertheless, the efficacy of GKAs in treating PCOS, particularly in the absence or presence of IR, remains uncertain. The meta-analysis protocol aims to address this knowledge gap, furnish evidence-based data to support potential revisions in PCOS treatment guidelines and promote the utilisation of GKAs in clinical settings.Methods and analysis A comprehensive search will be conducted across the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Embase, Medline, Scopus, CNKI, Wanfang and VIP databases to identify randomised controlled trials investigating the use of GKAs in the treatment of PCOS, irrespective of the presence of IR. The search will encompass all available studies without language restrictions and cover the period from the inception of each database to 10 April 2024. Disputes will be resolved by talking with a third expert following the screening of articles and data extraction by two reviewers. The primary outcomes of interest encompass changes in anthropometric parameters, menstrual frequency, sex hormone levels, and glucose metabolism, while secondary objectives include lipid metabolism and adverse events. The methodological quality of each study will be assessed using Version 2 of the Cochrane Collaboration tool for assessing Risk of Bias (RoB 2.0), and the Grade of Recommendations, Assessment, Development and Evaluation (GRADE) technique will be used to assess the quality of evidence and degree of recommendation. The study duration of this study will be from 5 April 2024 to 10 April 2025.Ethics and dissemination Since this study just analyses data that are readily available to the public and does not directly involve patient participation, ethical approval is not necessary. The findings will be made public by being published in a medical journal that is subject to peer review.PROSPERO registration number CRD42024535633.

Objective The impact and fracture of rockfall are important reasons for the difficulty in predicting movement trajectories, and the geometric characteristics of slope bodies are key factors affecting the movement. Methods To study the crushing process of rockfalls and the influence of slope geometry characteristics on the movement of rockfall blocks, discrete element method (PFC2D) simulation technology was used to establish a rockfall free-fall-impact model to analysethe rock mass structure and slope geometry characteristics of typical rockfall disaster points. The fragmentation process of rockfall under different fall heights and impact angles is analysed, and the block motion velocity, crack number and impact force are obtained. Moreover, the two-parameter Weibull distribution is used to describe the fragmentation degree of blocks. Results The experimental results reveal that the fracture process can be divided into three stages: Contact-disintegration, extrusion-fragmentation and independent movement. Rock mass fragmentation starts at the impact point, disintegration occurs along the structural plane first, and fragmentation occurs on the new fracture plane. Sudden changes of the block velocity, crack quantity and impact force occur in the contact-disintegration and compression-fragmentation stages. The block velocity plummets, exhibiting a "step effect", and the impact force rises sharply, revealing a "double peak phenomenon". Moreover, when the fall height increases or the impact angle decreases, the "step effect" and "double peak phenomenon" become more obvious. Under the same impact angle, an increase of the fall height results in the increase of impact kinetic energy, thus increasing the degree of fragmentation and decreasing the particle size distribution range and characteristic particle size. At the same fall height, an increase in the impact angle causes that the contact area is reduced, and the degree of breakage is reduced, increasing the particle size distribution range and characteristic particle size. Conclusion The present results provide technical support for revealing the impact fragmentation mechanism of rockfall slopes and predicting the trajectory of block motion.

The rise of the 6G wireless communication provides a broader prospect for the development of virtual reality panoramic video.The tile-based panoramic video coding scheme can improve the viewing experience of 360° video under the same condition of network bandwidth.Tile partition affects the video transmission performance.Compared with small tiles,using large tiles can effectively improve coding efficiency,but it will cause more pixel overhead by transmitting a larger area to cover the viewport.The existing tile partition work is mainly designed for the rectangular viewport,but the projection of spherical video to a two-dimensional plane will stretch different areas of the viewport to varying degrees in practice.Deriving the pixel overhead associated with covering irregular viewport areas with rectangular tiles is more complicated.To address this challenge,a tile partitioning algorithm for the user's real viewport has been proposed in this paper.Firstly,the stretching distortion of the viewport caused by the projection format is analyzed,and the pixel overhead of the irregular viewport with different tile partition sizes is derived.Secondly,by trading off the pixel overhead and the coding efficiency of tiles with different granularity,an optimal tile partition scheme has been proposed for the panoramic video sequence.Finally,the proposed scheme is compared with the exhaustive search method for tile partition in the experiment,and the results show that the proposed algorithm can achieve almost the same transmission efficiency as the exhaustive search method with less computational complexity.

In this paper a dynamical system model is proposed for solving the split convex feasibility problem. Under mild conditions, it is shown that the proposed dynamical system globally converges to a solution of the split convex feasibility problem. An exponential convergence is obtained provided that the bounded linear regularity property is satisfied. The validity and transient behavior of the dynamical system is demonstrated by several numerical examples. The method proposed in this paper can be regarded as not only a continuous version but also an interior version of the known CQ-method for solving the split convex feasibility problem. [ABSTRACT FROM AUTHOR]

The application of surfactant or surfactant-assisted media to grow polyoxometalate (POM)-based MOFs (POMOFs) is extremely scarce. In this work, for the first time, we use water-polyethylene glycol (PEG) 400 mixed media to synthesize two new crystalline POM-pillared three-dimensional porous arrays, [Co7(Trz)12(H2O)8][HPX12O40(VO)2]·12H2O (X = Mo for Co-PMo and X = W for Co-PW, Trz = 1,2,4-triazole). By employing a simple sonication-driven functionalization strategy, Co-PMo/CNTs (PCNT-n) nanocomposites with increased effective sites, enhanced specific surface area and excellent conductivity are fabricated. The resulting PCNT-2 nanocomposite shows an excellent reversible capacity of 820 mA h g−1 after 100 cycles and outstanding rate capability as an anode for lithium batteries. After the initial decay, the PCNT-2 electrode can bear a current density of 2000 mA g−1 over 450 cycles without obvious capacity loss. Meanwhile, the mechanism of lithium storage in PCNT-2 is discussed using X-ray photoelectron spectroscopy (XPS). Moreover, the PCNT-2 nanocomposite exhibits the hybrid behavior of battery and supercapacitor according to the electrochemical kinetic analyses. This might open new avenues for the design of crystalline POM-based materials or their nanocomposites to achieve high-performance energy storage. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to develop a novel formulation of oleanolic acid (OA) solid dispersion (SD), using leucine (Leu) as the carrier to improve OA oral bioavailability. Methods: The OA‐Leu SD was prepared by solvent evaporation and was evaluated in vitro using differential scanning calorimetry, X‐ray powder diffraction, scanning electron microscopy, flowability, hygroscopicity and dissolution test. The stability of the SD was evaluated using accelerated testing. In vivo pharmacokinetic tests were performed in male Sprague Dawley rats using a liquid chromatography tandem‐mass spectrometry bioanalytical method. Key findings: OA‐Leu SD was successfully prepared, and OA was mostly in an amorphous state. More than 80% of OA could dissolve in OA‐Leu SD in 20 min, while only 13.4% of free OA dissolved. The powder flow of OA‐Leu SD was clearly improved compared with free OA and its moisture absorption was 3.4%. The accelerated testing further demonstrated that SD could maintain OA in an amorphous state at 40 °C for 6 months. OA‐Leu SD showed higher relative oral bioavailability (189.7%) than free OA in rats. Conclusions: Using Leu as a carrier produced a SD with good flowability, low hygroscopicity and high bioavailability. [ABSTRACT FROM AUTHOR]

Background: Adiponectin (ADP) polymorphisms associated with diabetes mellitus in several populations. However, no previous studies have investigated its association with diabetic peripheral neuropathy (DPN). Our study examined the association between ADP-linked SNPs and DPN susceptibility. Methods: We randomly recruited 160 diabetes mellitus (DM) patients and 80 healthy individuals. Results: The C allele of rs3821799 increased DPN susceptibility. In normal individuals, GG of rs3774261 carriers had 7.1 times higher DPN susceptibility than AA carriers. The haplotype analyzes indicated CGG might increase DPN susceptibility. Conclusion: Our study demonstrated that ADP gene polymorphisms are associated with the susceptibility to DPN. [ABSTRACT FROM AUTHOR]

Objectives: To search for mutations in the Frizzled-4 gene (FZD4) in Chinese patients with familial exudative vitreoretinopathy (FEVR) and to delineate the mutation- associated clinical features. Methods: Forty-eight Chinese patients with FEVR and 100 unrelated control subjects were recruited and had complete ophthalmic examinations performed. The coding regions of FZD4 were screened for mutations by polymerase chain reaction and direct sequencing. Multiple sequence alignment was conducted to evaluate the conservation of residues among different FZD4 homologs and the human Frizzled family. Genotype-phenotype correlations were also analyzed. Results: Twelve putative disease-causing mutations were identified in total, 9 of which were novel: 1 deletion (P14fsX57), 1 nonsense mutation (S491X), and 7 missense mutations (G22E, E180K, T237R, R253C, F328S, A339T, and D470N). Three reported FZD4 mutations were also detected: H69Y, M105V, and W496X. Remarkably, 2 patients who harbored compound heterozygous mutations (H69Y with E180K orW496X) had amore severe ocular phenotype than carriers of a single H69Y mutation. Conclusions: FZD4 mutations were responsible for FEVR in 15 of 48 Chinese patients (31.3%) in this study, similar to other ethnic groups. This study supports the highly polymorphic nature of FZD4 with a differential mutation profile in the Chinese population. Clinical Relevance: The profile of the mutations obtained in FZD4 further illustrates the complexity of FEVR and provides a better understanding of the genotypephenotype correlations. [ABSTRACT FROM AUTHOR]

Antigen-adjuvant combination could induce a protective and long-lasting anti-tumor immune response. However, exploiting system which could co-deliver melanoma antigen peptide Trp2 (Tyrosinase-related protein 2) and Toll-like-receptor-7 (TLR7) agonists imiquimod (R837) both are poor aqueous solubility is still challenging. Our new nanocomplex was explored for specific delivery of Trp2 and R837 into antigen-presenting cells (APCs). R837 was loaded into mannosylated-β-cyclodextrin (Man-CD) to target dendritic cells (DCs) by binding mannose receptors (MR) on DCs. A fusion peptide (WT) was constructed by incorporating the amino acid region of TAT (cell-penetrating peptide) into Trp2 to improve the TAT-mediated intracellular efficiency. Negatively charged sodium alginate (SA), a biocompatible polymer, which can induce adjuvant responses by affecting the functions of DCs, was complexed with Man-CD/R837 and WT via physical adsorption. The optimized nanocomplex promoted the cellular uptake and showed remarkable efficacy to enhance the secreting of Th1-cytokines. This multi-functional nanocomplex system may allow effective targeting-codelivery of multi-hydrophobic drugs and be a promising subunit vaccine candidate as a potential prevention action of tumor. [ABSTRACT FROM AUTHOR]