Oncostatin M (OSM) has pleiotropic effects on various inflammatory diseases, including kidney stone disease. The prevalence of kidney stones has increased worldwide, despite recent therapeutic advances, due to its high recurrence rate, suggesting the importance of prevention of repeated recurrence in the treatment of kidney stone disease. Using a mouse model of renal crystal formation, we investigated the preventive effects of blockade of OSM receptor β (OSMRβ) signaling on the development of kidney stone disease by treatment with a monoclonal anti-OSMRβ antibody that we generated. The anti-OSMRβ antibody abrogated OSM-induced phosphorylation of STAT3 and expression of crystal-binding molecules (Opn, Anxa1, Anxa2) and inflammation/fibrosis-associated molecules (Tnfa, Tgfb, Col1a2) in renal tubular epithelial cells and fibroblasts. In glyoxylate-injected mice, a mouse model of renal crystal formation, there was significant suppression of crystal deposits and expression of crystal-binding molecules (Opn, Anxa1, Anxa2), a tubular injury marker (Kim-1), and inflammation/fibrosis-associated molecules (Tnfa, Il1b, Mcp-1, Tgfb, Col1a2) in the kidneys of the anti-OSMRβ antibody-treated mice, compared with those in vehicle- or isotype control antibody-treated mice. In addition, treatment with the anti-OSMRβ antibody significantly decreased infiltrating macrophages and fibrosis in the kidneys. These findings suggest that anti-OSMRβ antibody-treatment may be effective in preventing kidney stone disease.

Digital trade brings opportunities for the region to develop an open economy, and also leads to changes in regional green productivity and progress towards carbon neutrality. This study uses pilot policies of cross-border e-commerce cities as a quasi-experiment to examine how digital trade policies affect regional carbon emission efficiency. It is found that the carbon efficiency of the pilot cities was significantly improved after the intervention policy of digital trade. This conclusion is still supported by the entropy balance matching sample and the estimator after considering the heterogeneity treatment effect. Digital trade policies can help developing countries improve sustainable competitiveness and pursue carbon neutrality. In addition, digital trade can significantly promote regional energy productivity and green production technology, which is conducive to the improvement of carbon emission efficiency. These findings provide implications and insights for making low-carbon development policies in the era of digital trade.

For relaxor-ferroelectrics and relaxor-ferromagnets, the initial Ehrenfest-classification gives no phase-transition that contradicts the measured order-parameter, while the classification according to order-parameter and its derivatives raises the question about the relationships between the phase-transition and the specific-heat peak above and near the transition temperature. Here, based on the free-energy (F) of the thermodynamic limit systems when the external-field (h) tends 0, thermal equilibrium phase-transitions of thermodynamic limit systems with temperature (T) are reclassified into: (1) Discontinuous phase-transition. [Formula: see text] and [Formula: see text] have discontinuities in a T range; (2) Continuous phase-transition. [Formula: see text] and [Formula: see text] are continuous with T, while [Formula: see text] and [Formula: see text] have discontinuities at a T point; and (3) Diffuse phase-transition. [Formula: see text] and [Formula: see text] are continuous with T, while they are respectively equal to 0 at the transition-temperature (T) and diffuse-temperature (T). The diffuse-region of the phase-transition is [Formula: see text] and the diffuse-degree [Formula: see text], naturally giving the relation of the phase-transition to the specific-heat peak.

Every day, listeners encounter a wide range of acoustic signals. Successfully solving this variability problem allows them to interpret these signals accurately. While this mechanism tends to be less effortful for adults, children need to learn stable categories in the face of such variability. It is unknown to what extent general maturation or diversity of the input plays a role in shaping different speech categorization profiles that children can employ. Here, we tested school-aged children's speech categorization with a continuous speech categorization task called the Visual Analogue Scaling (VAS) task. We measured the linguistic diversity in each child's social environment through a social network analysis. We found that increased linguistic diversity led to more flexible and gradient speech categorization. On the other hand, less diverse linguistic input led to more categorical speech categorization. We argue that these findings have implications for speech perception as well as linguistic diversity research.

Regular physical activity is associated with healthier brains and improved cognition among older adults. Yet, the impact of a short bout of exercise on older adults' cognition still is not fully clarified. The present study explored the effects of 20 min of moderate-intensity aerobic exercise (on a cycle ergometer) on cognition. Forty-eight healthy older adults were randomly assigned to an exercise or a control group and completed four cognitive tests: Affective Go/No-Go (AGN), Simple Reaction Time (SRT), Spatial Working Memory (SWM) and a Backward Counting task. Tests were administered prior to and immediately after 20 min of cycling (exercise group) or rest (control group). Mixed-design 2 × 2 ANOVAs indicated a significant interaction of Group x Session, for commission errors on the positive valence of the Affective Go/No-go task, indicating that the exercise group performed better on one aspect of this inhibition test after cycling (p = 0.004), while the control group's performance declined after rest. A similar pattern was found for the SWM, with the exercise group showing a significantly better performance after the exercise both for total error (p = 0.027) and the strategy (p = 0.002), while no improvement was observed after rest (controls). The study suggests that inhibitory control functions and working memory may be improved by a single relatively short bout of moderate exercise. However, the null effects of exercise on the other cognitive measures indicate that the neurocognitive benefits of acute exercise for older adults may be selectively sensitive to exercise parameters and to specific aspects of cognition.

The world heritage object Nebra Sky Disc is one of the best investigated archaeological objects. The origin of the raw materials it is made of is well known. However, its manufacturing process was not completely clear. Investigations were made in order to clarify the steps of manufacturing from the initial casting to the finished disc using the latest metallographic techniques. Therefore, a small piece from the outer part of the disc was investigated and compared with a replica. Both were prepared regarding the metallographic procedure. Microstructural analysis was made by optical microscopy on a colour etched surface, EDS and electron backscatter diffraction. For the investigation of mechanical properties microhardness measurements were made. It could be found that the Nebra Sky Disc was manufactured from a flat cast followed by hot forging process. During the forging process the disc was heated and forged for approximately 10 times.

Jute endophyte Staphylococcus hominis strain MBL_AB63 was reported to produce a novel antimicrobial peptide, 'homicorcin'. This exhibits potential activity against a broad spectrum of Gram-positive bacteria. Eight genes were predicted to be involved in the sequential maturation of this peptide antibiotic, which includes structural (homA), dehydratase (homB), cyclase (homC), peptidase (homP), immunity (homI), oxidoreductase (homO), ATP-binding cassette transporter (homT1), and permease (homT2), respectively. Among the modification enzymes, HomB, HomC, and HomP exhibit sequence similarities with class I lantibiotic dehydratase, cyclase, and leader peptidase, respectively. The current study investigated the sequential modifications and secretion of homicorcin by constructing robust computational protein models and analyzing their interaction patterns using protein-protein docking techniques. To enhance comprehension of the protein arrangement, their subcellular localization was also extrapolated. The findings demonstrate a network of proteins that works in a synchronized manner, where HomC functions as an intermediary between HomB and the transporter (HomT). Following its dehydration by HomB and cyclization by HomC, the pro-homicorcin is taken out of the cell by the transporter and processed by HomP, resulting in the production of matured, processed homicorcin. This biosynthesis model for homicorcin will lay the groundwork for the sustainable and efficient production of this peptide antibiotic.

Understanding the dynamics of movements between different demographic events is essential for informing effective population management strategies. This study aims to characterize the trajectories of demographic and other vital events within the Nairobi Urban Health and Demographic Surveillance System (NUHDSS). Thus, it intends to unravel patterns and trends that can guide the development of targeted policies and interventions to address the population's evolving needs. Using a continuous-time homogeneous multi-state Markov model, longitudinal data from 223,350 individuals in Korogocho and Viwandani urban slums, we study the enumeration, births, deaths, and migrations among urban poor in Nairobi, shedding light on population dynamics and movements over time, disaggregated by gender. Findings indicate a positive net migration in population per thousand in 2002, dropping in 2004, with Viwandani consistently showing higher birth rates than Korogocho. Males generally have higher death rates than females. Females from Viwandani are 39.0% more likely to exit after enumeration compared to Korogocho, while males are 35.6% more likely to move from enumeration to exit compared to males from Korogocho. Both genders from Viwandani have a decreased likelihood of moving from birth to death compared to Korogocho. Our findings provide unique insights into migration in urban Kenya, the frequency and movement to different demographic events and any gender differences that warrant strategic policies for effective population and health planning in Africa. These findings can inform the design of effective health interventions that are often affected by migration and population growth.

Cholinergic treatments with an emphasis on M1 muscarinic acetylcholine receptor (mAChR) agonists as potential modulating agents are a new approach in Alzheimer's disease (AD) therapy. In previous research, we designed and characterized novel thiazolidine-2,4-dione (TZD)-derived compounds that possess anti-AD properties and enhance the expression of mAChRM1 in rats. This study evaluated a novel orthosteric agonist of mAChRM1 from related pathways that has shown promising anti-Alzheimer's disease activity. PC12 cells were exposed to various concentrations of TZ4M before they were exposed to scopolamine (3 µM). Immunocytochemistry and western blot analyses revealed that TZ4M increased the expression of mAChRM1 in differentiated cells induced by scopolamine-treated PC12 cells. The results showed that TZ4M (3 and 5 µM) markedly upregulated PKC and ChAT protein expression, and the cells were significantly protected against increased ROS levels followed by neuronal cell loss, as evidenced by the MTT assay. TUNEL staining indicated that TZ4M impeded the shaping of apoptotic bodies. Analysis of the amino acid sequences of the ligand-protein binding site indicated that TZ4M is bound to the orthosteric site (acetylcholine site). This study revealed that TZ4M, a derivative of TZD, effectively protects against scopolamine-induced damage. TZ4M, a novel mACRM1 orthosteric agonist, is promising for treating AD.

The mucociliary clearance (MC) system is a vital host defense against infection in the lung. MC system function is dependent on ciliary density, structure, and function and airway surface liquid (ASL) composition and hydration. Animal and human studies indicate that MC rate decreases with age which may contribute to the increased rates of pulmonary infection experienced by older people. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene encodes an anion channel on epithelial surfaces that plays a key role in maintaining ASL hydration. Failure or dysfunction of CFTR could result in the dehydration of airway mucus, depressing MC. Here we use two available databases including bulk (GTEx) and single-cell (CELLxGENE) sequencing data from the lung to determine if CFTR expression decreases with age. Bulk expression data and single-cell expression data from goblet, club, and respiratory basal cells all demonstrated patterns of decreasing CFTR expression with age. Ciliated airway cells did not. Secretory cells (including club and goblet cells) and basal cells are the largest source of CFTR expression in the airway. This indicates that changes in CFTR expression and ASL dehydration may contribute to the decreasing MC associated with aging.

Accumulating evidence has shown that tRNA-derived small RNAs (tsRNAs) play crucial roles in malignant tumor development. However, whether serum tsRNAs can act as potential biological markers for hepatocellular carcinoma (HCC) are still largely unknown. In the current study, a novel tsRNA, namely tsRNA-Thr-5-0015, was prominently elevated in the sera of HCC patients than that of hepatitis cases and healthy check-ups, and it was related with TNM stage and lymphatic metastasis of HCC patients. Moreover, methodological evaluation confirmed that tsRNA-Thr-5-0015 had excellent stability, precision, accuracy and linear range. Additionally, the combined detection of serum tsRNA-Thr-5-0015 with AFP as well as PIVKA-II improved the diagnostic sensitivity for HCC. Furthermore, dynamic monitoring found that the serum tsRNA-Thr-5-0015 was drastically decreased in the postoperative HCC patients. Besides, Kaplan-Meier analysis displayed that patients with high level of serum tsRNA-Thr-5-0015 had shorter overall survival than that of the low level ones. In addition, bioinformatic prediction unveiled that the downstream targets of tsRNA-Thr-5-0015 were enriched in several signaling pathways, such as MAPK, PI3K-Akt, etc. In summary, tsRNA-Thr-5-0015 may be a promising biomarker for HCC diagnosis, therapeutic effect assessment and prognosis judgement. Especially, the combination with serum tsRNA-Thr-5-0015, AFP and PIVKA-II can enhance the diagnostic efficiency for HCC.

To explore the association between 25-hydroxy vitamin D [25-(OH)-D], interleukin-4 (IL-4), and interferon-γ (IFN-γ) in children with Mycoplasma pneumoniae (MP) infection-related asthma. Logistic analysis was conducted to compare general data in MP asthma and MP non-asthma groups. The level of 25-(OH)-D, IL-4, and IFN-γ were detected and compared between groups. Moreover, the receiver operating characteristic curve (ROC) was applied to test the predictive value of each variable. The results of logistic regression analysis demonstrated that recurrent upper respiratory tract infections and collective living are related to the incidence of MP infection whether with asthma or without asthma. IL-4 and IFN-γ in MP asthma group were significantly higher than those in MP non-asthma group and control group (p < 0. 05), whilst 25-(OH)-D and IFN-γ/IL-4 in MP asthma group were significantly lower than those in MP non-asthma group and control group (p < 0. 05). ROC curves indicated that the area under the curve (AUC) of 25-(OH)-D, IL-4, IFN-γ, IFN-γ/IL-4, and joint detection are 0.765, 0.780, 0.853, 0.638, and 0.912 in diagnosis of MP infection-related asthma, and sensitivity and specificity of joint detection are both greater than 95%. For children with MP infection-related asthma, the level of IL-4 and IFN-γ is upregulated, while 25-(OH)-D is downregulated. The joint detection of 25-(OH)-D, IL-4, IFN-γ, and IFN-γ/IL-4 may improve diagnostic capabilities of MP infection-related asthma.

This work is to investigate the diagnostic value of a deep learning-based magnetic resonance imaging (MRI) image segmentation (IS) technique for shoulder joint injuries (SJIs) in swimmers. A novel multi-scale feature fusion network (MSFFN) is developed by optimizing and integrating the AlexNet and U-Net algorithms for the segmentation of MRI images of the shoulder joint. The model is evaluated using metrics such as the Dice similarity coefficient (DSC), positive predictive value (PPV), and sensitivity (SE). A cohort of 52 swimmers with SJIs from Guangzhou Hospital serve as the subjects for this study, wherein the accuracy of the developed shoulder joint MRI IS model in diagnosing swimmers' SJIs is analyzed. The results reveal that the DSC for segmenting joint bones in MRI images based on the MSFFN algorithm is 92.65%, with PPV of 95.83% and SE of 96.30%. Similarly, the DSC for segmenting humerus bones in MRI images is 92.93%, with PPV of 95.56% and SE of 92.78%. The MRI IS algorithm exhibits an accuracy of 86.54% in diagnosing types of SJIs in swimmers, surpassing the conventional diagnostic accuracy of 71.15%. The consistency between the diagnostic results of complete tear, superior surface tear, inferior surface tear, and intratendinous tear of SJIs in swimmers and arthroscopic diagnostic results yield a Kappa value of 0.785 and an accuracy of 87.89%. These findings underscore the significant diagnostic value and potential of the MRI IS technique based on the MSFFN algorithm in diagnosing SJIs in swimmers.

Radiofrequency ablation (RFA) is effective treatment for Barrett's esophagus (BE). Product of successful RFA is neosquamous epithelium (NSE), which resembles native squamous epithelium and has lower risk for neoplastic transformation. Dilated intercellular spaces (IS) are common microscopic feature of reflux induced injury of esophagus. The aim of this study was to analyze the ultrastructure of NSE by transmission electron microscopy (TEM), depending on the post RFA treatment modalities and to asses impact of these findings on BE recurrence. Prospective observational clinical study based on TEM analysis of biopsy of specimens obtained from patients in whom CE of BE was achieved minimum 6 months after the last RFA session. In each patient biopsies were taken from NSE and proximal esophagus. Two groups of patients were defined according to the post RFA treatment: proton pump inhibitors (PPI's) or laparoscopic Nissen fundoplication (LNF). Comparative analysis of IS length was made between two groups. Endoscopic surveillance with biopsies was conducted for 5 years. Overall 22 patients with CE of BE after RFA underwent complete study protocol, out of whom in 10 LNF was performed, while 12 were treated with PPI's. The mean values of IS length in the proximal esophagus and NSE in LNF group were 0.378 ± 0.116 µm and 0.878 ± 0.354, while in PPI's group 0.724 ± 0.325 µm and 1.228 ± 0.226 µm, respectively. Mean lenghts of IS were statistically significantly higher in PPI's group both in NSE (p = 0.032) and proximal esophagus (p = 0.009). There were 5 BE recurrences after 5 years surveillance, 4 in PPI group and 1 in LNF group, without statistical significance (p = 0.084). Dilated IS are commonly presented in NSE of patients with CE of BE with RFA who are treated with PPI's. LNF provides may offer better reflux protection of NSE than PPI's and may reduce the rates of recurrence after successful RFA treatment.

Oncolytic virotherapy is a promising form of cancer treatment that uses viruses to infect and kill cancer cells. In addition to their direct effects on cancer cells, the viruses stimulate various immune responses partly directed against the tumour. Efforts are made to genetically engineer oncolytic viruses to enhance their immunogenic potential. However, the interplay between tumour growth, viral infection, and immune responses is complex and not fully understood, leading to variable and sometimes counterintuitive therapeutic outcomes. Here, we employ a spatio-temporal model to shed more light on this interplay. We investigate systematically how the properties of virus-induced immunogenic signals (their half-life, rate of spread, and potential to promote T-cell-mediated cytotoxicity) affect the therapeutic outcome. Our simulations reveal that strong immunogenic signals, combined with faster diffusion rates, improve the spread of immune activation, leading to better tumour eradication. However, replicate simulations suggest that the outcome of virotherapy is more stochastic than generally appreciated. Our model shows that virus-induced immune responses can interfere with virotherapy, by targeting virus-infected cancer cells and/or by impeding viral spread. In the presence of immune responses, the mode of virus introduction is important, with systemic viral delivery throughout the tumour yielding the most favourable outcomes. The timing of virus introduction also plays a critical role; depending on the efficacy of the immune response, a later start of virotherapy can be advantageous. Overall, our results emphasise that the rational design of oncolytic viruses requires optimising virus-induced immunogenic signals and strategies that balance viral spread with immune activity for improved therapeutic success.

Emerging evidence from neurophysiological brain vital sign studies show repeatable sensitivity to cumulative subconcussive impairments over a season of contact sports. The current study addressed the need for research comparing a low-contact control group to high-contact group. Importantly, the study also expanded the scope of neurophysiological changes related to repetitive head impacts to include female athletes in addition to male athletes. In total, 89 high school student athletes underwent 231 brain vital sign scans over a full calendar year. The results replicated prior subconcussive cognitive impairments (N400 delays) and sensory impairments (N100 amplitude reductions) in male athletes and demonstrated similar subconcussive impairments for the first time in female athletes. While there was no significant subconcussive difference between female and male athletes, female athletes show overall larger responses in general. The findings demonstrated that subconcussive impairments are detectable in a controlled experimental comparison for both female and male high school athletes. The study highlights the opportunity to monitor subconcussive changes in cognitive processing for both female and male athletes to help advance prevention, mitigation and management efforts aimed at reducing athletes' risk of potential long-term negative health outcomes related to cumulative exposure to repetitive head impacts.

The relationship between the oxidative balance score (OBS) and the serum Klotho level has yet to be defined. We sought to investigate the potential relationship between OBS and the serum Klotho level in the U.S. population aged 40-79 years. This study included 8,145 participants from the National Health and Nutrition Examination Surveys (NHANES) database spanning from 2007 to 2016. The OBS consisted of the dietary OBS and the lifestyle OBS, based on 16 dietary components and 4 lifestyle components. Weighted multiple linear regressions were performed to explore the association between OBS and serum Klotho level. Furthermore, nonlinear relationships were analyzed through the application of restricted cubic splines (RCS). In the multivariate linear regression model with adjustment for such as demographics, economic income and dietary intake, a higher OBS was associated with a higher serum Klotho, with the beta estimate and 95%CI of 2.85 (1.03-4.68, p < 0.01). Compared with the lowest tertile group, the highest group was associated with a higher Klotho level (30.35, 3.43-57.28, p < 0.05). Furthermore, higher dietary OBS and lifestyle OBS were similarly associated with higher Klotho level (beta (95%CI): 1.27 (0.79-3.32); 14.23 (9.53-18.92), respectively). The RCS exhibited a linear dose-response association between OBS, dietary OBS and lifestyle OBS with serum Klotho concentration (P>0.05). The association between OBS and serum Klotho level was consistent across age, sex, education, marital status, energy intake and poverty income ratio (PIR) (P>0.05). The study reported significant association between OBS and klotho, indicating that adherence to antioxidant behaviors may be linked to slower aging and better health.

A novel and environmentally friendly route was developed for production of sustainable flame retardant, antibacterial and UV protective nanoparticles for polymeric films nanocomposites. For the first time, dried molokhia leaves were engineered into spherical nanoparticles with an average size of 8.5 nm via an eco-friendly, one-pot solid-state ball-milling method. The engineered nanoparticles were proved using spectroscopic and microscopic techniques. The sustainable nanoparticles were employed as an efficient and green flame retardant, antibacterial and UV protective materials for polyvinyl alcohol (PVA) nanocomposite films. The distinct compatibility between PVA chains and spherical nanoparticles afford excellent homogeneous dispersion of each nanoparticle in the polymer matrix. Compared to blank PVA film which burned at a rate of 125 mm/min, the novel nanoparticles achieved significant flame retardancy for polymer nanocomposites films recording zero rate of burning. Their outstanding charring ability and naturally doped elemental composition were attributed to their higher flame retardancy achieved. Moreover, the newly developed multifunctional nanoparticles integrated outstanding UV protection feature to developed polymer nanocomposite films recording UV protection factor superiority of more than 900% compared to nanoparticle free film. Noteworthy to note that, the nanoparticles afford excellent inhibition to bacterial growth against Escherichia coli and Staphylococcus aureus over the surface of developed polymer nanocomposite films achieving clear inhibition zone of 9 and 7.6 mm compared to zero mm for pristine polymer film, respectively. In addition, a proposed and clarified flame retardancy mechanism was presented. Additionally, an assessment was conducted regarding the economic feasibility of producing sustainable multifunctional nanoparticles on an industrial scale.

Lack of health knowledge can be a main cause of barriers to early diagnosis and treatment, and it can also highlight the deficiencies in health education. Therefore, it is essential to understand the health knowledge needs of individuals and the related influencing factors in order to improve health education models. A total of 935 administrative staff (AS) were selected as study participants by convenience sampling in Yuxi City, China. An electronic questionnaire, comprising four parts-Health Knowledge Needs, Sociodemographic Characteristics, Health Psychology and Behavior, and Self-Reported Medical History-were used to collect data. Statistical analysis was conducted using an internal consistency test, Kruskal-Wallis test, principal component analysis, hierarchical clustering analysis, and binary logistic regression analysis, performed with SPSS version 19.0. The Health Knowledge Needs Questionnaire had a Cronbach's α of 0.883 and a Guttman Split-Half coefficient of 0.907. The need rates for health knowledge exceeding 30% are as follows: Traditional Chinese Medicine, Hypertension, Weight Management, Dietary Nutrition and Food Hygiene, Hyperlipidemia, Gastrointestinal Diseases, Heart Diseases, and First Aid. Health knowledge needs were summarized into six dimensions: "Diseases with Low Health Knowledge Needs", "Maternal and Child Health Care and Thyroid Diseases", "Cardiovascular and Cerebrovascular Diseases and Malignancies", "Health Preservation and First Aid", "The Four Highs Syndrome", and "Respiratory and Digestive Diseases". Gender, self-rated economic pressure, family size, and self-reported number of diseases were identified as influencing factors of health knowledge needs (P < 0.05). Thus, precision health education should be conducted according to the health knowledge needs of the target group, and various health knowledge topics should be organically integrated into modular health education to improve its efficiency.

In this randomized controlled trial, we assessed the effects of three consecutive intra-silicone oil (SO) injections of methotrexate (MTX) on the outcomes of surgery for proliferative vitreoretinopathy grade C (PVR-C). Seventy-four eyes of 74 patients with PVR-C were included. Of these, 37 eyes were assigned to the MTX group and 37 eyes to the control group. Fourteen patients failed to comply with the 6-month follow-up period. All eyes underwent vitrectomy and SO injection. In the MTX group, 250 µg MTX was injected into the SO after surgery and at weeks 3 and 6 postoperatively. The primary outcome was the retinal reattachment rate at 6 months. The secondary outcomes included limited PVR recurrence and adverse events. Retinal reattachment was achieved in 22 eyes (73.3%) in the MTX group and 23 eyes (76.7%) in the control group (difference: -3.4%, 95% CI: -25.2-18.5%). Limited PVR recurrence was observed in one eye (4.5%) in the MTX group versus nine eyes (39.1%) in the control group at 6 months (P = 0.01). No adverse effects were observed. Adjunctive treatment with three consecutive applications of intra-SO MTX did not reveal a significant effect on the retinal re-detachment rate but could statistically significantly reduce limited PVR recurrence.Trial registration: http//ClinicalTrials.gov NCT04482543, 22/07/2020.

Roof breaking is the root cause of rock burst and mine earthquake. However, the classical "thin plate theory" and "thick plate theory" cannot fully reveal the mechanical mechanism of the influence of roof thickness-span ratio on the fracture mode. In this paper, based on the cohesive element technology, the mechanical behavior of cohesive element failure was studied according to the maximum nominal stress criterion and BK fracture criterion, and the fracture mechanical behavior of roofs with different thicknesses fixed on four sides under uniform load was numerically simulated. The fracture pattern and the maximum principal stress evolution laws of roofs with different thicknesses were obtained. The results show that there are three fracture modes of the plates with different thickness: pure tensile fracture mode at the bottom surface, mixed fracture mode around the "X" shape crack, and pure shear fracture mode along the long edge boundary. The crack morphology of thin plate is the transverse "O-X" type, and the crack morphology of thick plate is the "O-❋" type. With the increase of thickness, the tensile-shear mixed failure mode gradually changes from the tensile dominant to the shear dominant.