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Abstract Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between meniscus pathologies and KOA radiographic progression remains unclear. We conducted an observational study in the Osteoarthritis Initiative (OAI) cohort, with a 48-month follow-up. Meniscus pathology and synovitis were measured by MRI osteoarthritis knee score (MOAKS) at baseline and 24 months, and a comprehensive synovitis score was calculated using effusion and Hoffa synovitis scores. The knee osteoarthritis radiographic progression was considered that Kellgren–Lawrence (KL) grade and joint space narrowing (JSN) grade at 48 months were increased compared to those at baseline. This study included a total of 589 participants, with KL grades mainly being KL1 (26.5%), KL2 (34.1%), and KL3 (30.2%) at baseline, while JSN grades were mostly 0 at baseline. A logistic regression model was used to analyze the relationship between meniscus pathology, synovitis, and KOA progression. Mediation analysis was used to evaluate the mediation effect of synovitis. The average age of the participants was 61 years old, 62% of which were female. The medial meniscus extrusion was longitudinally correlated with the progression of KL (odds ratio [OR]: 2.271, 95% confidence interval [CI]: 1.412–3.694) and medial JSN (OR: 3.211, 95% CI: 2.040–5.054). Additionally, the longitudinal correlation between medial meniscus damage and progression of KOA (OR: 1.853, 95% CI: 1.177–2.941) and medial JSN (OR: 1.655, 95% CI: 1.053–2.602) was significant. Synovitis was found to mediate the relationship between medial meniscus extrusion and KL and medial JSN progression at baseline (β: 0.029, 95% CI: 0.010–0.053; β: 0.022, 95% CI: 0.005–0.046) and beyond 24 months (β: 0.039, 95% CI: 0.016–0.068; β: 0.047, 95% CI: 0.020–0.078). However, we did not find evidence of synovitis mediating the relationship between meniscal damage and KOA progression. Synovitis mediates the relationship between medial meniscus extrusion (rather than meniscus damage) and KOA progression.

Gastric cancer (GC), a malignant tumor, is highly prevalent, particularly in Asia. miR-509-3p plays a crucial role in regulating tumorigenesis, but its mechanism in GC remains unclear. Potential targets of miR-509-3p were identified through database analysis (miRWalk, TargetScan, ENCORI, and TCGA). The binding site between miR-509-3p and forkhead box protein M1 (FOXM1) was confirmed using a dual-luciferase assay. CCK-8, EdU, Transwell, wound healing assays, flow cytometry, and Western blot analysis were employed to examine changes in proliferation, migration, invasion, apoptosis, FOXM1, and the p38 MAPK (p38)/MAPK-activated protein kinase 2 (MK2) pathway in GC cells (MNK-45 and HGC-27) after miR-509-3p overexpression or knockdown, FOXM1 overexpression, and application of the p38 pathway agonist Anisomycin. The size and weight of subcutaneous xenografts were measured, and the effects of miR-509-3p overexpression were analyzed through histopathological staining (Tunel immunofluorescence, HE staining, Ki67, and FOXM1 immunohistochemistry). The results showed that overexpression of miR-509-3p suppressed proliferation, migration, and invasion while accelerating apoptosis. Knockdown of miR-509-3p promoted malignant progression. miR-509-3p inhibited GC by regulating FOXM1-mediated p38/MK2 pathway activation, and miR-509-3p mimics restrained tumor growth in vivo through this pathway. In conclusion, miR-509-3p suppresses GC malignant progression by regulating FOXM1-mediated p38/MK2 pathway activation.

Abstract Objective The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies. Methods This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs). Results Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein–protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages. Conclusion Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation.

Objective: The article aims to provide genetic counseling to a family with two children who were experiencing growth and developmental delays.Methods: Clinical information of the proband was collected. Peripheral blood was collected from core family members to identify the initial reason for growth and developmental delays by whole exome sequencing (WES) and Sanger sequencing. To ascertain the consequences of the newly discovered variants, details of the variants detected were analyzed by bioinformatic tools. Furthermore, we performed in vitro experimentation targeting SNX14 gene expression to confirm whether the variants could alter the expression of SNX14.Results: The proband had prenatal ultrasound findings that included flattened frontal bones, increased interocular distance, widened bilateral cerebral sulci, and shortened long bones, which resulted in subsequent postnatal developmental delays. The older sister also displayed growth developmental delays and poor muscle tone. WES identified compound heterozygous variants of c.712A>T (p.Arg238Ter) and .2744A>T (p.Gln915Leu) in the SNX14 gene in these two children. Both are novel missense variant that originates from the father and mother, respectively. Sanger sequencing confirmed this result. Following the guideline of the American College of Medical Genetics and Genomics (ACMG), the SNX14 c.712A>T (p.Arg238Ter) variant was predicted to be pathogenic (P), while the SNX14 c.2744A>T (p.Gln915Leu) variant was predicted to be a variant of uncertain significance (VUS). The structural analysis revealed that the c.2744A>T (p.Gln915Leu) variant may impact the stability of the SNX14 protein. In vitro experiments demonstrated that both variants reduced SNX14 expression.Conclusion: The SNX14 gene c.712A>T (p.Arg238Ter) and c.2744A>T (p.Gln915Leu) were identified as the genetic causes of growth and developmental delay in two affected children. This conclusion was based on the clinical presentations of the children, structural analysis of the mutant protein, and in vitro experimental validation. This discovery expands the range of SNX14 gene variants and provides a foundation for genetic counseling and guidance for future pregnancies in the affected children’s families.

Highlights A multifactorial and oriented scaffolds was constructed to stimulate osteochondral regeneration. This is the first demonstration that both drug and gene nanoparticles were spatially deposited on a patterned film through metal-ligand interactions. For the first time, film-rolling approach was employed to construct osteochondral plug to mimick the Haversian canal structure of natural bone.

The sandy cobble stratum presents a high risk for underground tunnel construction due to its low cohesive properties and susceptibility to loosening and falling. The use of Advanced ductule for grouting reinforcement inevitably results in vibrations, and understanding how these vibrations propagate is crucial in selecting tunnel engineering support schemes and responding to accident risks. Based on a bored tunnel under construction in Xi’an, field vibration propagation characteristics testing were carried out for advanced ductile installation. The time-history response and frequency distribution characteristics of the vibration velocity within the tunnel face under sandy cobble stratum conditions were studied, and the law of vibration propagation attenuation within the tunnel face range was obtained. The results showed that: 1) During the conduit drilling process, the tunnel face mainly experienced vertical vibrations, with the horizontal velocity amplitude accounting for only 15%–20% of the vertical velocity amplitude. At a distance of 1.0 m from the conduit, the vertical velocity amplitude reaches 10.602 mm/s, and the vibration energy concentrates mainly in the frequency range of 150–250 Hz. At a distance of 1.5 m from the conduit, the bidirectional vibration velocity significantly attenuates; 2) The vibration characteristics within the tunnel face can be classified into three primary areas: “Loose and Falling” area, “Significant Vibration” area, and “Vibration Attenuation” area. Loose, falling and significant vibrations occurred mainly within a range of about 1.25 m around the conduit. 3) As the diameter of the conduit decreases, the amplitude of vertical vibration velocity decreases by about 20%. By reducing the design diameter of the advanced ductule in a reasonable manner, it is possible to effectively mitigate the impact of vibration caused by the sandy cobble stratum during installation. This can yield a positive impact, curtailing the occurrence of the tunnel’s collapse phenomenon and ensuring its stability.

Continuous large amounts of precipitation can lead to a rapid increase in the water content of concrete in village building foundations, which can adversely affect the mechanical properties, such as the compressive strength of concrete. There are few experimental studies on the compressive stochastic mechanical properties of concrete in the wet state after considering different soaking times (different water contents and saturations), but there is no corresponding stochastic damage principal structure model. In this study, the mechanical properties of concrete under different immersion times were tested to obtain the mechanical properties of the concrete degradation law, and the random damage intrinsic model of wet concrete was established. The results of this paper were compared with the classical test results from the literature to verify the validity of the model. The results show that the proposed stochastic damage model is able to consider both the effects of the saturation and the damage behavior of wet concrete under compression, which is beneficial to the structural design and maintenance protection of village buildings in areas with abundant precipitation.

BackgroundIn recent studies, individual scapular anatomy has been found to be related to degenerative full-thickness rotator cuff tears. However, research on the relationship between the anatomical characteristics of shoulder radiographs and bursal-sided partial-thickness rotator cuff tears (PTRCTs) is limited, and the risk factors for this pathology still need to be determined.MethodsThe bursal-sided PTRCTs group included 102 patients without a history of shoulder trauma who underwent arthroscopy between January 2021 and October 2022. A total of 102 demographically matched outpatients with intact rotator cuffs were selected as the control group. Radiographs were used to measure the lateral acromial angle (LAA), critical shoulder angle (CSA), greater tuberosity angle (GTA), β-angle, acromion index (AI), acromiohumeral distance (AHD), acromial tilt (AT), acromial slope (AS), acromial type, and acromial spur by two independent observers. Multivariate analyses of these data were used to identify potential risk factors for bursal-sided PTRCTs. Receiver operating characteristic (ROC) analysis was performed to assess the sensitivity and specificity of CSA, GTA, and AI for this type of pathology.ResultThe β-angle, AHD, AS and acromion type showed no difference between bursal-sided PTRCTs and controls (p = 0.009, 0.200, 0.747 and 0.078, respectively). CSA, GTA and AI were significantly higher in bursal-sided PTRCTs (p

BackgroundBirthweight have profound impacts on health status throughout lifetime, however, the relationship between maternal ferritin level in pregnancy and birthweight of the newborn remains controversial.ObjectiveThis retrospective cohort research was to analyze the association between maternal ferritin levels during pregnancy with birthweight outcomes, primarily for low birthweight (LBW) and small for gestational age (SGA).MethodsNewborns weighing lower than 2,500 grams were defined as LBW. SGA is defined as birthweight lower than the 10th percentile of the distribution of newborns' birthweight of the same gestational age. Multivariable logistic regressions have been used to explore the association of maternal ferritin levels and birthweight related outcomes, in which the ferritin concentration was logarithm transformed in the model. We further used restricted cubic spline models to explore linear/non-linear dose–response manners of ferritin level and birthweight outcomes.ResultsA total of 3,566 pregnant women were included in the study. In the results of the present study, we observed that maternal ferritin levels were linearly associated with the risk of LBW (p-trend = 0.005) and SGA (p-trend = 0.04), with the adjusted odds ratios (ORs) of 1.78 (95% CI 1.37–2.32) for LBW and 1.87 (95% CI 1.38–2.54) for SGA with an increase in Ln-ferritin concentrations per unit. The adjusted ORs across quartiles of ferritin levels were 2.14 (95% CI 1.03–4.47) for Quartile 2, 3.13 (95% CI 1.47–6.69) for Quartile 3, and 3.63 (95% CI 1.52–8.68) for Quartile 4 for LBW. The adjusted ORs of LBW and SGA among women using supplemental iron were 0.56 (95% CI 0.38, 0.85) and 0.65 (95% CI 0.40, 1.05) compared with non-users, respectively.ConclusionsOur findings found a linear dose–response relationship between ferritin levels and an increased risk of poor birthweight outcomes, suggesting that maternal ferritin level during pregnancy may provide an additional predictor for differentiating poor birthweight related outcomes. Further exploration should be conducted to ensure maternal ferritin thresholds and iron supplement doses.

Matrix metalloproteinase 9 (MMP9) is an important member of the matrix metalloproteinase family and plays a key role in balancing extracellular matrix proteins. Studies have shown that the homozygous mutations in MMP9 can lead to metaphyseal anadysplasia type 2 (MANDP2, OMIM#613073). The clinical phenotype of this disease is limited and there were only five reported cases of MANDP2 associated with homozygous MMP9 mutations from three families. In this study, we described a case of a fetus with skeletal system malformation. The main clinical manifestations include the short bilateral femur, absence of right fibula, and curved ipsilateral tibia with short length. Importantly, two novel compound heterozygous variants of the MMP9 gene (NM_004,994.3: c.151C > T and c.929del) were found through the trio whole exome sequencing and Sanger sequencing. This is the first report that identified the compound heterozygous variants of the MMP9 gene associated with metaphyseal dysplasia type 2.

Winter jujube fruit is susceptible to aging, peel reddening, dehydration, shrinkage, and tissue softening during shelf life after it is removed from the cold storage conditions. In this study, the effects of 1-methylcyclopropene (1-MCP) and salicylic acid (SA) on the quality of winter jujube fruit during shelf life were investigated by measuring physiological indexes and the activities of antioxidant enzymes and enzymes related to reactive oxygen species (ROS) metabolism of winter jujube fruit. The results showed that 1-MCP treatment and SA treatment suppressed weight loss, respiratory rate, malondialdehyde (MDA) content, H2O2 content, and O2-· production rate, but improved firmness, color difference (ΔE), soluble solid content (SSC), titratable acidity (TA), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), phenylalanine ammonia-lyase (PAL) activities, ascorbic acid content, glutathione content, total phenolic content, and total flavonoid content in comparison with the control. Particularly, the combined treatment of 1-MCP and SA (1-MCP+SA treatment) showed the maximum efficacy compared to the 1-MCP treatment and SA treatment alone. 1-MCP+SA treatment exhibited the best preservation effect, followed by SA treatment and 1-MCP treatment. Thus, the combined treatment of 1-MCP and SA is an effective approach to maintain the postharvest quality of winter jujube fruit and extend the shelf life.

In recent years, it has been found that adjusting the organizational structure of Co3O4 through solid solution and other methods can effectively improve its catalytic performance for the oxidation of low concentration methane. Its catalytic activity is close to that of metal Pd, which is expected to replace costly noble metal catalysts. Therefore, the in-depth research on the mechanism and methods of Co3O4 microstructure regulation has very important academic value and economic benefits. In this paper, we reviewed the catalytic oxidation mechanism, microstructure regulation mechanism, and methods of nano-Co3O4 on methane gas, which provides reference for the development of high-activity Co3O4-based methane combustion catalysts. Through literature investigation, it is found that the surface energy state of nano-Co3O4 can be adjusted by loading of noble metals, resulting in the reduction of Co–O bond strength, thus accelerating the formation of reactive oxygen species chemical bonds, and improving its catalytic effect. Secondly, the use of metal oxides and non-metallic oxide carriers helps to disperse and stabilize cobalt ions, improve the structural elasticity of Co3O4, and ultimately improve its catalytic performance. In addition, the performance of the catalyst can be improved by adjusting the microstructure of the composite catalyst and optimizing the preparation process. In this review, we summarize the catalytic mechanism and microstructure regulation of nano-Co3O4 and its composite catalysts (embedded with noble metals or combined with metallic and nonmetallic oxides) for methane combustion. Notably, this review delves into the substance of measures that can be used to improve the catalytic performance of Co3O4, highlighting the constructive role of components in composite catalysts that can improve the catalytic capacity of Co3O4. Firstly, the research status of Co3O4 composite catalyst is reviewed in this paper. It is hoped that relevant researchers can get inspiration from this paper and develop high-activity Co3O4-based methane combustion catalyst.

Exploring the delay causality between airports and comparing the delay propagation patterns across different airport networks is critical to better understand delay propagation mechanisms and provide effective delay mitigation strategies. A novel attention-based recurrent graph convolutional neural network is proposed to identify the hidden delay causality relationship among airports in three different airport networks of China. The selected three airport networks show great heterogeneities in topological characteristics, such as average intensity, modularity and eigenvector centrality. The modeling results indicate that the identified delay causality networks of three airport networks are greatly varied in terms of complexity, delay propagation distance and efficiency. Moreover, the delay state of each airport is categorized into three levels, and the delay state transition of the three networks is explored. The results indicate that delay state transition in the North China Control Area exhibits an obvious bidirectional transition form that mainly propagates between the large-degree airports and small-degree airports, while severe delays of some hub airports account for a relatively large proportion in the other two networks. The results of this study could better reveal the delay propagation mechanism among airports and help airport operators develop effective strategies to alleviate flight delays and improve airport operation efficiency.

The aim of this study was to investigate the potential protective effects of walnut oligopeptides (WOPs) on indomethacin-induced gastric ulcers in rats. The rats were divided into the following groups: normal group, model group, omeprazole group (0.02 g/kg), and WOPs groups (0.22, 0.44, and 0.88 g/kg, respectively). After receiving gavage once per day for 30 consecutive days, the rats were injected intraperitoneally with indomethacin 48 mg/kg to induce gastric ulcers. Then, the serum inflammatory cytokines and gastric prostaglandin E2 (PGE2), oxidative stress-related indicators, and the RNA expression of COX-1 and COX-2 were measured. The results revealed that WOPs confer significant gastroprotection on gastric ulcers caused by indomethacin, regulating inflammatory cytokines, oxidative stress, and prostaglandins synthesis, and enhancing the expression of COX-1 and COX-2 in gastric tissue, thus exerting its protective effect on gastric mucosa. The gastroprotective mechanism may be related to the involvement of the arachidonic acid metabolism and upregulation of tryptophan, phenylalanine, tyrosine, and alpha-Linolenic acid metabolism synthesis in vivo.

Organoids well recapitulate organ-specific functions from their tissue of origin and remain fundamental aspects of organogenesis. Organoids are widely applied in biomedical research, drug discovery, and regenerative medicine. There are various cultivated organoid systems induced by adult stem cells and pluripotent stem cells, or directly derived from primary tissues. Researchers have drawn inspiration by combination of organoid technology and tissue engineering to produce organoids with more physiological relevance and suitable for translational medicine. This review describes the value of applying organoids for tumorigenesis modeling and tumor vaccination. We summarize the application of organoids in tumor precision medicine. Extant challenges that need to be conquered to make this technology be more feasible and precise are discussed.

Aging-related muscle loss is a hallmark of aging and is the cause of some negative outcomes. An optimized diet and supplements have a positive effect in slowing down the process of muscle loss. This study was designed to evaluate the beneficial effects of walnut oligopeptides (WOPs) on aging-related muscle loss and explore the possible underlying mechanism in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice. SAMP8 mice were randomly divided into four groups (n = 15/group), including one group which was the SAMP8 age control group and three groups those were WOP intervention groups. Meanwhile, Senescence Accelerated Resistant Mouse 1 (SAMR1) mice (n = 12), which had normal senescence rates, were used as model controls. During the six-month intervention period, the age control and normal control groups were given sterilized water, while the three WOP intervention groups were given WOP solution with low (110 mg/kg·bw), medium (220 mg/kg·bw) and high concentrations (440 mg/kg·bw), respectively. The results showed that WOPs could significantly increase muscle mass and improve physical performance (wire hang and catwalk behavioral tests) in aging mice. Moreover, WOPs could significantly reduce the levels of IL-1β, IL-6 and TNF-α in serum and gastrocnemius tissues and increase the mitochondrial DNA content, as well as the expression levels of AMPK, PGC-1α, NRF-1 and TFAM in the gastrocnemius muscle of aging mice, which was speculated to be the specific mechanism related to mitochondrial function improvement and inflammation reduction. These results indicate that WOPs can improve aging-related muscle loss, in term of both muscle mass and physical performance, and WOP supplements seems to be potentially effective in elderly individuals.

The authors would like to correct spelling mistakes (undenatured type II collagen) in the title, as well as in the main manuscript including the tables and figures in the title paper [...]

Ageing-related bone impairment due to exposure to hyperglycemic environment is scarcely researched. The aim was to confirm the improvement effects of undenatured type II collagen (UC II) on bone impairment in ageing db/db mice, and the ageing model was established by normal feeding for 48-week-old. Then, the ageing db/db mice were randomly assigned to UC II intervention, the ageing model, and the chondroitin sulfate + glucosamine hydrochloride control groups. After 12 weeks of treatment, femoral microarchitecture and biomechanical parameters were observed, biomarkers including bone metabolism, inflammatory cytokines, and oxidative stress were measured, and the gastrocnemius function and expressions of interleukin (IL) 1β, receptor activator of nuclear factor (NF)-κB ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) were analyzed. The results showed that the mice in the UC II intervention group showed significantly superior bone and gastrocnemius properties than those in the ageing model group, including bone mineral density (287.65 ± 72.77 vs. 186.97 ± 32.2 mg/cm3), gastrocnemius index (0.46 ± 0.07 vs. 0.18 ± 0.01%), muscle fiber diameter (0.0415 ± 0.005 vs. 0.0330 ± 0.002 mm), and cross-sectional area (0.0011 ± 0.00007 vs. 0.00038 ± 0.00004 mm2). The UC II intervention elevated bone mineralization and formation and decreased bone resorption, inflammatory cytokines, and the oxidative stress. In addition, lower protein expression of IL-1β, RANKL, and TRAP in the UC II intervention group was observed. These findings suggested that UC II improved bones impaired by T2DM during ageing, and the likely mechanism was partly due to inhibition of inflammation and oxidative stress.

Peptic ulcer has a serious impact on people’s health around the world, and traditional medicines can cause adverse reactions. This study investigated the protective effects of tilapia collagen oligopeptides (TCOPs) on gastroduodenal injury. Seventy-two specific pathogen-free (SPF) male Sprague Dawley (SD) rats were randomly divided into six groups according to body weight: normal control group, ethanol group, whey protein group (500 mg/kg BW), and three TCOPs dose groups (250, 500, 1000 mg/kg BW). After intragastric administration for 30 days, the acute gastroduodenal injury was induced by anhydrous ethanol (5 mL/kg, intragastrically) in all groups except the normal control group. Biomarkers in gastric and duodenal tissue and serum were measured. Furthermore, western blot was used to detect the expression of apoptosis-related proteins. The results showed that the administration with TCOPs significantly reduced gastric and duodenal ulcer index, increased gastric juice pH, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, along with the reduction of malondialdehyde (MDA) contents. TCOPs decreased tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and myeloperoxidase (MPO) levels, while interleukin– 10 (IL-10) levels were increased. Furthermore, pepsinogens 1 (PG1), pepsinogens 2 (PG2), gastrin (GAS), and the pepsinogen ratio (PGR) were decreased, the prostaglandin E2 (PGE2) and NO contents were increased after TCOPs intervention. Moreover, TCOPs up-regulated the expression of Bcl-2 and inhibited the expression of Bax and Caspase-3. In conclusion, TCOPs have protective effects on ethanol-induced gastroduodenal injury through gastrointestinal mucosal microcirculation promotion, antioxidation, anti-inflammation, and anti-apoptosis mechanisms.