Objective: To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

Objective: To systematically evaluate the influencing factors for repeated implantation failure (RIF) after in vitro fertilization-embryo transfer (IVF-ET) in China, so as to provide the evidence for prevention of RIF. Methods: Literature on influencing factors for RIF in China were retrieved from CNKI, Wanfang Data, VIP, China Medical Literature Service System, PubMed, Web of Science, Cochrane Library and Embase from inception to September, 2024. A meta-analysis was performed using RevMan 5.3 and Stata 14.0 softwares. Literature were excluded one by one for sensitivity analysis. Publication bias was evaluated using Egger's test. Results: Initially 4 836 relevant articles were retrieved, and 12 of them were finally included, with a total sample size of 11 554 individuals. There were 10 case-control studies, 1 cohort study, and 1 cross-sectional study; and 10 high-quality studies and 2 medium-quality studies. The meta-analysis showed that factors including advanced age (OR=1.121, 95%CI: 1.035-1.215), prolonged infertility duration (OR=1.237, 95%CI: 1.091-1.403), abnormal hysteroscopy findings (OR=2.205, 95%CI: 1.119-4.348), positive anti-nuclear antibody (ANA) (OR=2.393, 95%CI: 1.473-3.886), and positive anti-beta2 glycoprotein Ⅰ antibody (β2-GPⅠ-Ab) (OR=2.824, 95%CI: 1.987-4.013) were associated with an increased risk of RIF; while factors including the large number of embryos transferred (OR=0.309, 95%CI: 0.098-0.973), thicker endometrium (OR=0.601, 95%CI: 0.556-0.650), and higher granulocyte colony-stimulating factor (G-CSF) levels (OR=0.657, 95%CI: 0.511-0.845) were associated with a reduced risk of RIF. Conclusion IVF-ET RIF is associated with age, infertility duration, number of embryos transferred, endometrial thickness, hysteroscopy findings, G-CSF levels, ANA and β2-GPⅠ-Ab.

Dendrobium moniliforme (D. moniliforme) is a traditional medicinal herb widely cultivated in Asia. Flavonoids, one of the largest groups of secondary metabolites in plants, are significant medicinal components in Dendrobium species. Several subgroups of R2R3-MYB proteins have been validated to directly regulate flavonoid biosynthesis. Using PacBio sequencing technology, we assembled a high-quality chromosome-level D. moniliforme genome with a total length of 1.20 Gb and a contig N50 of 3.97 Mb. The BUSCO assessment of genome annotation was 91.4%. By integrating the genome and transcriptome, we identified biosynthesis pathway enzyme genes related to flavonoids, polysaccharides, carotenoids, and alkaloids. A total of 90 R2R3-MYBs were identified in D. moniliforme and classified into 21 subgroups. Studies on the functions of R2R3-MYB transcription factors revealed that R2R3-MYB in SG6 can up-regulate flavonoid biosynthesis. Various validation experiments, including subcellular localization, transient overexpression, UPLC-MS/MS, HPLC, yeast one-hybrid, and dual-luciferase assays, demonstrated that DMYB69 directly up-regulates the expression of enzyme genes involved in flavonoid biosynthesis, increasing the content of flavonoids such as anthocyanin, flavone, and flavonol. Additionally, DMYB44 was shown to directly up-regulate the expression of carotenoid biosynthesis enzyme genes, thereby increasing carotenoid content. This study provides an essential genome resource and theoretical basis for molecular breeding research in D. moniliforme.

Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEO_x-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEO_x) by ester bonds. AEO_x-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEO_x-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEO_x-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEO_x-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.

Pulpitis is a common infective oral disease in clinical situations. The regulatory mechanisms of immune defense in pulpitis are still being investigated. Osteomodulin (OMD) is a small leucine-rich proteoglycan family member distributed in bones and teeth. It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells (hDPSCs). In this study, the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated. The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining. Intriguingly, the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens. The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide (LPS)-induced inflammation. A conditional Omd knockout mouse model with pulpal inflammation was established. LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice, whereas OMD administration exhibited a protective effect against pulpitis. Mechanistically, the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB (NF-κB) signaling pathway. Interleukin-1 receptor 1 (IL1R1), a vital membrane receptor activating the NF-κB pathway, was significantly downregulated in OMD-overexpressing hDPSCs. Additionally, the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking. In vivo, excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist. Overall, OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway. OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
Pulpitis/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction ; Humans ; Mice ; Mice, Knockout ; Dental Pulp/metabolism* ; Disease Models, Animal ; Lipopolysaccharides

Objective:To explore the interaction effects on brain activity between the smoking addiction and weight status by resting-state functional magnetic resonance imaging.Methods:Retrospective analysis of clinical data and resting-state functional magnetic resonance imaging data were analyzed from 99 recruited subjects from January 2019 to December 2021. All participants were divided into four groups: overweight smokers ( n=24), normal-weight smokers ( n=28), overweight non-smokers ( n=19), and normal weight non-smokers ( n=28). Calculate regional homogeneity (ReHo) to reflect the internal brain activity of the subjects. Two-way ANOVA was used to detect the interaction effects between smoking addiction and overweight on ReHo by SPM12 software, correcting for age, years of education and head motion. Results:The interaction effect between smoking addiction and overweight on ReHo was significant in right superior frontal gyrus(x, y, z=15, 9, 60)(GRF corrected, Pvoxel<0.005, Pcluster<0.05). The ReHo value in the right superior frontal gyrus of overweight smokers was significantly higher than that of normal weight smokers ( t=3.768, P<0.001, Bonferroni corrected). The ReHo values in the right superior frontal gyrus of overweight non-smokers were significantly lower than those of normal weight non-smokers ( t=-3.242, P=0.002, Bonferroni corrected). The ReHo values in the right superior frontal gyurs of normal-weight smokers were significantly lower than those of normal weight non-smokers( t=-3.540, P=0.001, Bonferroni corrected). The ReHo values in the right superior frontal gyrus of overweight smokers were significantly higher than those of overweight non-smokers ( t=3.392, P=0.002, Bonferroni corrected). Correlation analyses showed that the strengthen ReHo value in right superior frontal gyrus was positively associated with pack-year in smoking addicts( r=0.387, P=0.007, Bonferroni corrected). Conclusion:Smoking addiction and overweight have an antagonistic effect on brain activity in the right superior frontal gyrus, which may provide potential therapeutic targets for individuals with comorbidity of smoking addiction and overweight.

Objective To investigate the effects of calcium and integrin-binding protein 1(CIB1)on the cell proliferation,invasion,apoptosis,and migration of triple-negative breast cancer cells and its possible mechanism.Methods MDA-MB-231 and MDA-MB-468 cells were divided into CIB1-knockdown(infected with CRISPR/Cas9 lentivirus)and negative-control groups.Cell Counting Kit-8(CCK-8)and 5-ethynyl-2′-deoxyuridine(EdU)assays were performed to detect cell proliferation.Cell apoptosis was determined through flow cytometry.Scratch and Transwell experiments were conducted to measure the migration and invasion abilities of cells.The mRNA and protein expression levels of β-catenin,adenomatous polyposis coli(APC),glycogen synthase kinase 3β(GSK-3β),and c-myc were detected via real-time quantitative polymerase chain reaction and Western blot.Results Compared with the negative-control group,the CIB1-knockdown group showed decreased cell proliferation,invasion,and migration(P<0.05)and increased cell apoptosis(P<0.05).The mRNA and protein expressions of β-catenin,APC,and c-myc decreased(P<0.05),and that of GSK-3β increased(P<0.05).Conclusion CIB1 knockdown can inhibit cell proliferation,invasion,and migration and promote the apoptosis of breast cancer cells.Its mechanism may be related to the inhibition of Wnt/β-catenin signaling pathway.

Objective:To explore the dynamic temporal variability of brain functional networks in individuals with internet gaming disorder(IGD)using dynamic functional connectivity density(dFCD).Methods:From January 2019 to December 2021, resting-state functional magnetic resonance imaging data were recruited from 55 patients with IGD and demographically matched 50 healthy controls.Data analysis was performed by IBM SPSS 21.0 software. The functional connectivity density(FCD) combined with sliding window analysis was employed to calculate the temporal variability of global functional connectivity.FCD in whole brain was further devided into ipsilateral and cotralateral parts.The temporal variability of dFCD was further quantified utilizing the standard deviations of whole brain, intra-, and inter-hemispheric FCD. Finally, Pearson correlation analysis was performed between dFCD variance in differential brain regions and clinical behaviors.Results:The inter-hemispheric dFCD in the left posterior cingulate cortex(-0.16±0.24) and the left precuneus(-0.08±0.23) in patients with IGD were lower that those in healthy controls(0.002±0.260, 0.12±0.36)( t=-3.502, -4.160, both P<0.05).And the intra-hemispheric dFCD in the left calcarine, the left precuneus, and the left posterior cingulate cortex in patients with IGD were lower that those in healthy controls( t=-3.809, -4.360, -3.561, all P<0.05).Moreover, abnormal global dFCD variability of the calcarine and ipsilateral dFCD variability of the PCC negatively correlated with the severity of IGD( r=-0.380, -0.413, both P<0.05). Conclusion:Patients with IGD show intra-and inter-hemispheric dFCD differences in the visual attention network and default mode network, which may respond to the underlying neurobiological basis for the presence of cognitive dysfunction and impaired concentration.

Recurrent ulcerative colitis is a difficult point in clinical treatment.Its TCM property is deficiency in nature and excess in superficiality.Deficiency of spleen yang for a long time will affect the kidney;if Taiyang and Shaoyin meridians are attacked for a long time,Jueyin will be involved.San yin diseases will occur,and yang qi will be severely injured;dampness and heat,turbid poison,cold coagulation,food stagnation and other pathogenic factors invade and attack from outside to inside,lie down in the intestinal collaterals,remove heat by stasis,fumigate the lipid membrane and form internal ulcers.Deficiency of healthy qi,weakness and sores are the origin of the disease,stagnation of intestinal collaterals is the superficiality of the disease,and"stasis"as the main pathological factor carries out the disease from beginning to end.According to the idea of supporting sores and removing blood stasis,the self-made Xiaoyong Yukui Decoction can support sores to generate new ones,remove blood stasis and eliminate stagnation,and help regulate cold and heat,so as to strengthen the health and reduce toxin,remove blood stasis and unblock collaterals,so that the pathogenic factors can be removed and health can be restored,and the internal ulcer can heal,achieving good clinical efficacy in treating recurrent ulcerative colitis.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.