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Oral squamous cell carcinoma (OSCC), with high potential for metastasis, is the most common malignant tumor of the head and neck. Cancer-associated fibroblasts (CAFs) are the main stromal cells in the microenvironment and aggravate tumor progression. However, whether CAFs are associated with the progression of OSCC remains unknown and the underlying mechanism remains unclear. In the present study, the role of CAFs in mediating OSCC cell migration and invasion was investigated, and the participation of exosomal miR-382-5p in this process was elucidated. In this study, according to the α-SMA staining with immunohistochemistry, 47 OSCC patients were divided into CAFs-rich and CAFs poor groups, and association of CAF density and clinicopathologic features of the OSCC patients were analyzed with Pearson χ2 test. Transwell assay was used for evaluating cell migration and invasion ability of OSCC cells after being co-cultured with NFs or CAFs, or after added exosomes. qPCR was used to detect the expression of miR-382-5p. Western blot analysis was used to measure the expression of migration and invasion-associated proteins. In the present study, the CAF density in tumor tissues was found to be relevant to OSCC lymph node metastasis and TNM stage. Furthermore, we revealed that miR-382-5p was overexpressed in CAFs compared with that in fibroblasts of adjacent normal tissue and miR-382-5p overexpression was responsible for OSCC cell migration and invasion. Finally, we demonstrated that CAF-derived exosomes transported miR-382-5p to OSCC cells. The present study confirmed a new mechanism of CAF-facilitated OSCC progression and may be beneficial for identifying new cancer therapeutic targets.

Background The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. Methods In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001–2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. Results Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284–1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. Conclusions There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

Background The maternal-to-zygotic transition (MZT) is a critical process in early human development, involving the degradation of maternal gene transcripts and activation of zygotic genes. Any disruption in the degradation of maternal transcripts may be associated with some reproductive disorders. However, the precise mechanism by which maternal gene transcripts are degraded during this transition remains unclear. Results Through an analysis of weighted gene co-expression networks, an oocyte-specific module was identified, showing high consistency with the expression pattern of maternal transcripts degraded at the 8-cell stage, which is associated with the cell cycle and transcription factor binding. Within this module, a maternal long non-coding RNA known as OIP5 antisense RNA 1 ( OIP5-AS1 ) was identified. It was observed that OIP5-AS1 can bind to the RNA binding protein human antigen R (HuR), potentially limiting its availability for other mRNAs and contributing to the degradation of maternal transcripts during MZT. Moreover, RNA immunoprecipitation sequencing in human induced pluripotent stem cells (iPSCs) revealed HuR and OIP5-AS1 are likely to tightly bind together and involved in functions related to the cell cycle and transcriptional regulation. Upon knocking down OIP5-AS1 and the ELAVL1 gene, which encodes the HuR protein in human iPSCs, a significant reduction in the expression levels of maternal transcripts was observed, suggesting an essential role of these factors in regulating maternal transcript stability during early development. Conclusions The HuR protein plays a critical role in influencing the degradation of maternal transcripts during the MZT in early human embryonic development. Understanding the role of OIP5-AS1 in regulating HuR protein could provide valuable insights into developmental biology and potentially lead to new therapeutic strategies for developmental disorders.

Additionally, BA.1, BA.2, BA.4/5, and BF.7 exhibited susceptibility to BA.2.76 breakthrough infection serum samples; however, BA.2.75 showed more resistance than BA.2 and BA.4/5 (figure E). [...]BA.2.75 is more resistant to breakthrough BF.7 infection neutralisation than BA.2 and BA.4/5. [...]comparisons showed that BA.5.1.2 breakthrough infections induced a broader antibody response against the tested subvariants and induced significantly higher geometric mean titres against BQ.1 and BQ.1.1 compared with delta, BA.1, BA.2.2, BA.2.76, or BF.7 breakthrough infections (figure; appendix p 7). Omicron subvariants BQ.1 and BQ.1.1 with increased resistance to neutralising antibodies can pose a challenge to immunity induced by vaccination or infection and render therapeutic monoclonal antibodies ineffective.3–6 Our results suggest that BQ.1 and BQ.1.1 extensively, but incompletely, escape omicron subvariant breakthrough infection neutralisation, including the most recent BA.5.1.2, BA.2.76, and BF.7 infections.

Background Insulin resistance, represented by increased triglyceride-glucose (TyG) index levels, shows interplay with visceral obesity and together promotes cardiovascular diseases and mortality. However, significant controversies exist regarding whether modified TyG indices, such as TyG-BMI, TyG-WC, and TyG-WHtR, outperform the TyG index in predicting cardiovascular outcomes. We aimed to explore whether there was a synergistic effect of a body shape index (ABSI), a better parameter reflecting visceral obesity, and the TyG index on cardiovascular mortality. Methods We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2001–2018 of 17,329 individuals. The associations of the TyG index and ABSI with cardiovascular mortality were investigated via Cox regression analysis and restricted cubic splines. Receiver operating characteristic (ROC) curve analysis was performed to compare the predictive value. Mediation analysis was used to explore the potential mediator. Results A total of 673 (3.9%) cardiovascular deaths occurred during a median follow-up of 8.92 years. Individuals with high TyG and high ABSI (TyG > 9.04 and ABSI > 0.085) were at the highest cardiovascular mortality risk both in individuals with (HR = 1.714, 95% CI 1.123–2.616) and without diabetes (HR = 1.402, 95% CI 1.003–1.960), suggesting a synergistic effect. Next, we multiplied these two indicators and established TyG-ABSI. It showed a J-shaped relationship and a positive linear relationship with cardiovascular mortality in individuals with and without diabetes, respectively. Arterial stiffness, represented by estimated pulse wave velocity, partially mediated the effect of TyG-ABSI on cardiovascular mortality, with a mediation proportion of 42.7%. The predictive value of TyG-ABSI was greater than that of the TyG index, TyG-BMI, TyG-WC, and TyG-WHtR (Harrell’s C-index: 0.710 vs 0.623 vs 0.539 vs 0.612 vs 0.622, all p  < 0.001). Conclusions The simultaneous assessment of the TyG index and ABSI revealed a synergistic effect on cardiovascular mortality. We recommended the use of TyG-ABSI instead of the TyG index and other modified TyG indices in cardiovascular risk assessment.

Background To explore the associations of computed tomography (CT) image features with the serum cryptococcal antigen (CrAg) titers measured by the lateral flow assay (LFA) in localized pulmonary cryptococcosis patients. Methods A retrospective analysis of patients with pathologically confirmed pulmonary cryptococcosis admitted to the First Affiliated Hospital of Xiamen University from January 2016 to December 2022 was performed. Clinical data, CT results, serum CrAg-LFA test results, and follow-up data were collected and analyzed. Results A total of 107 patients with localized pulmonary cryptococcosis were included, of which 31 had a single lesion in chest CT and the other 76 had multiple lesions. The positivity rate was (94.74% vs 64.52%) and titers of serum CrAg-LFA (1.77 ± 0.87 vs 0.91 ± 0.98) in the multiple lesion group were higher than those in the single lesion group, respectively. Multivariate linear regression analysis showed that the serum CrAg titers were positively associated with the number of lesions (β, 0.08; 95% CI, 0.05 to 0.12) and the lesion size (β, 0.40; 95% CI, 0.31 to 0.50) after adjusting other covariates. The serum CrAg-LFA titers of 60 pulmonary cryptococcosis patients showed a decreasing trend with the reduction in pulmonary lesion size after effective therapy. Conclusion In pulmonary cryptococcosis patients, the number and size of lung lesions are positively correlated with the titers of the serum CrAg-LFA test. The CrAg-LFA test could be a useful tool for the diagnosis, severity assessment, and therapeutic monitoring of localized pulmonary cryptococcosis patients.

Background Gastric cancer is one of the most common malignant tumors of the digestive system. However, its targeted therapy develops at a slow pace. Thus, exploring the mechanisms of the malignant behavior of gastric cancer cells is crucial to exploit its treatment. Mammalian never-in-mitosis A (NIMA)-related kinases (NEKs) are considered to play a significant role in cancer cell proliferation. However, no study has reported on NIMA family proteins in gastric cancer. Methods Bioinformatics analysis was employed to clarify the expression patterns of NEK1–NEK11 and their effects on prognosis. The effects of NEK7 on immune infiltration and NEK7 related pathways were also analyzed. At the cell level, 5-ethynyl-2-deoxyuridine, cell cycle, and Cell Counting Kit-8 assays were utilized to clarify the effect of NEK7 on gastric cancer cell proliferation. A mouse subcutaneous model revealed the regulating effect of NEK7 on gastric cancer cell proliferation in vivo. Results Bioinformatics analysis revealed that NEK7 is upregulated in gastric cancer and is related to poor prognosis. NEK7 is also related to T-stage, which is closely associated with cell proliferation. Further analysis showed that NEK7 was correlated with infiltration of multiple immune cells as well as gastric cancer-related pathways. Cell experiments indicated the promoting effect of NEK7 on cell proliferation, while the absence of NEK7 could lead to inhibition of gastric cancer proliferation and G1/S arrest. Conclusion NEK7 exerts a regulatory effect on cell proliferation and is closely related to tumor immune infiltration.

Abstract Repairing damage in the craniofacial skeleton is challenging. Craniofacial bones require intramembranous ossification to generate tissue-engineered bone grafts via angiogenesis and osteogenesis. Here, we designed a mineralized collagen delivery system for BMP-2 and vascular endothelial growth factor (VEGF) for implantation into animal models of mandibular defects. BMP-2/VEGF were mixed with mineralized collagen which was implanted into the rabbit mandibular. Animals were divided into (i) controls with no growth factors; (ii) BMP-2 alone; or (iii) BMP-2 and VEGF combined. CT and hisomputed tomography and histological staining were performed to assess bone repair. New bone formation was higher in BMP-2 and BMP-2-VEGF groups in which angiogenesis and osteogenesis were enhanced. This highlights the use of mineralized collagen with BMP-2/VEGF as an effective alternative for bone regeneration.

The aim of the present study was to investigate the effects of advanced glycation end products (AGEs) and berberine hydrochloride (BBR) on the osteogenic differentiation ability of human periodontal ligament stem cells (hPDLSCs) in vitro, and their underlying mechanisms. hPDLSCs were subjected to osteogenic induction and were treated with AGEs or AGEs + BBR. Following varying numbers of days in culture, alkaline phosphatase (ALP) activity assays, ALP staining, alizarin red staining, ELISAs, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were performed to determine the osteogenic differentiation ability of hPDLSCs; RT-qPCR, western blot analysis, and immunofluorescence staining were conducted to investigate the underlying mechanisms. The canonical Wnt/β-catenin pathway inhibitor XAV-939 and agonist CHIR-99021 were used to determine the contribution of the canonical Wnt/β-catenin pathway to differentiation. Treatment with AGEs resulted in reduced ALP activity and Collagen I protein levels, decreased ALP staining, fewer mineralized nodules, and downregulated expression of osteogenic-specific genes [Runt-related transcription factor 2 (Runx2), Osterix, ALP, osteopontin (OPN), Collagen I and osteocalcin (OCN)] and proteins (Runx2, OPN, BSP and OCN); however, BBR partially rescued the AGE-induced decrease in the osteogenic potential of hPDLSCs. Furthermore, AGEs activated the canonical Wnt/β-catenin signaling pathway and promoted the nuclear translocation of β-catenin; BBR partially attenuated this effect. In addition, XAV-939 partially rescued the AGE-induced reduction in the osteogenic potential of hPDLSCs, whereas CHIR-99021 suppressed the BBR-induced increase in the osteogenic potential of hPDLSCs. The present study indicated that AGEs attenuated the osteogenic differentiation ability of hPDLSCs, in part by activating the canonical Wnt/β-catenin pathway; however, BBR attenuated these effects by inhibiting the canonical Wnt/β-catenin pathway. These findings suggest a role for BBR in periodontal regeneration induced by hPDLSCs in patients with diabetes mellitus.

The vacuum drainage pipe (VDP) pile is a new type of pipe pile on which the current research is mainly focused on laboratory tests. There is little research on bearing characteristics and carbon emissions in practical engineering. To further explore the bearing capacity and sustainable construction of vacuum drainage pipe piles, static load tests were conducted to investigate the single-pile bearing capacity of ordinary pipe piles and vacuum drainage pipe piles, as well as soil settlement monitoring around the piles. Then, the Q-S curves of the two piles, the pile-side friction resistance under different pile top loads, and the development law of pile end resistance were compared and analyzed. Finally, based on the guidelines of the IPCC, the energy-saving and emission-reduction effects of VDP piles in practical engineering were estimated. The results indicate that, after vacuum consolidation, the VDP pile basically eliminates the phenomenon of soil compaction and does not cause excessive relative displacement of the pile and soil. VDP piles have increased lateral friction resistance, and compared to traditional piles, their ultimate bearing capacity is increased by 17.6%. Compared with traditional methods, the VDP pile method can reduce carbon emissions by 31.4%. This study provides guidance for the production and design of future VDP piles and demonstrates the potential of VDP piles for energy conservation and emission reduction in comparison to traditional methods.