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Colorectal cancer (CRC) is one of the most common cancers and a major cause of mortality. The present study aimed to identify potential biomarkers for CRC metastasis and uncover the mechanisms underlying the etiology of the disease. The five datasets GSE68468, GSE62321, GSE22834, GSE14297 and GSE6988 were utilized in the study, all of which contained metastatic and non-metastatic CRC samples. Among them, three datasets were integrated via meta-analysis to identify the differentially expressed genes (DEGs) between the two types of samples. A protein-protein interaction (PPI) network was constructed for these DEGs. Candidate genes were then selected by the support vector machine (SVM) classifier based on the betweenness centrality (BC) algorithm. A CRC dataset from The Cancer Genome Atlas database was used to evaluate the accuracy of the SVM classifier. Pathway enrichment analysis was carried out for the SVM-classified gene signatures. In total, 358 DEGs were identified by meta-analysis. The top ten nodes in the PPI network with the highest BC values were selected, including cAMP responsive element binding protein 1 (CREB1), cullin 7 (CUL7) and signal sequence receptor 3 (SSR3). The optimal SVM classification model was established, which was able to precisely distinguish between the metastatic and non-metastatic samples. Based on this SVM classifier, 40 signature genes were identified, which were mainly enriched in protein processing in endoplasmic reticulum (e.g., SSR3), AMPK signaling pathway (e.g., CREB1) and ubiquitin mediated proteolysis (e.g., FBXO2, CUL7 and UBE2D3) pathways. In conclusion, the SVM-classified genes, including CREB1, CUL7 and SSR3, precisely distinguished the metastatic CRC samples from the non-metastatic ones. These genes have the potential to be used as biomarkers for the prognosis of metastatic CRC.

Bacteria identified in the oral cavity are highly complicated. They include approximately 1000 species with a diverse variety of commensal microbes that play crucial roles in the health status of individuals. Epidemiological studies related to molecular pathology have revealed that there is a close relationship between oral microbiota and tumor occurrence. Oral microbiota has attracted considerable attention for its role in in‐situ or distant tumor progression. Anaerobic oral bacteria with potential pathogenic abilities, especially Fusobacterium nucleatum and Porphyromonas gingivalis, are well studied and have close relationships with various types of carcinomas. Some aerobic bacteria such as Parvimonas are also linked to tumorigenesis. Moreover, human papillomavirus, oral fungi, and parasites are closely associated with oropharyngeal carcinoma. Microbial dysbiosis, colonization, and translocation of oral microbiota are necessary for implementation of carcinogenic functions. Various underlying mechanisms of oral microbiota‐induced carcinogenesis have been reported including excessive inflammatory reaction, immunosuppression of host, promotion of malignant transformation, antiapoptotic activity, and secretion of carcinogens. In this review, we have systemically described the impact of oral microbial abnormalities on carcinogenesis and the future directions in this field for bringing in new ideas for effective prevention of tumors. Oral microbiota has been playing an important role in the development of cancer throughout human body. Thus we try to summarize the current researches about this topic.

Maternal psychological distress during pregnancy is associated with unfavorable outcomes in infants. Mindfulness-based interventions (MBIs) can effectively alleviate psychological distress, but there are often barriers to the access of face-to-face interventions. This study aimed to investigate the effectiveness of a digital guided self-help (GSH) MBI (GSH-MBI) in reducing maternal psychological distress and improving infant neuropsychological performance. This was a randomized controlled trial. We recruited 160 women who were 12 to 20 weeks pregnant and exhibited psychological distress. We randomized them into a digital GSH-MBI group and a control group (usual perinatal care). The digital GSH-MBI consisted of a 6-week intervention through a WeChat mini program, with a daily reminder sent to the participants by a research assistant via WeChat. The primary outcomes consisted of maternal psychological distress, including depression, anxiety, and pregnancy-related anxiety symptoms, which were assessed at 6 time points from baseline to 6 months post partum (only pregnancy-related anxiety symptoms were assessed 3 times during pregnancy). The secondary outcomes were infant neuropsychological outcomes, including temperament and developmental behaviors, which were assessed at 6 weeks and 6 months post partum. Compared with the control group, the digital GSH-MBI group showed a significant reduction in depression, anxiety, and pregnancy-related anxiety symptoms. In addition, the scores of the digital GSH-MBI group were lower than those of the control group for the 3 types of infant temperament at 6 weeks post partum, including quality of mood, distractibility, and adaptability. Digital GSH-MBIs are effective in alleviating psychological distress among pregnant women and protecting infant outcomes. Chinese Clinical Trial Register ChiCTR2000040717; https://www.chictr.org.cn/showproj.aspx?proj=65376.

Background SARS-CoV-2, which has brought a huge negative impact on the world since the end of 2019, is reported to invade cells using the spike (S) protein to bind to angiotensin-converting enzyme II (ACE2) receptors on human cells while the transmembrane protease serine 2 (TMPRSS2) is the key protease that activates the S protein, which greatly facilitates the entry of SARS-CoV-2 into target cells. In our previous study, it was observed that the positive rate of SARS-CoV-2 nucleic acids in saliva was higher in male and the elderly COVID-19 patients, suggesting that the susceptibility of oral tissues to SARS-CoV-2 may be related to gender and age. This research aimed to further investigate the SARS-CoV-2 susceptibility in oral tissues and influencing factors from the perspective of ACE2 and TMPRSS2, which were two proteins closely associated with SARS-CoV-2 infection. Methods Immunofluorescence was used to find the localization of ACE2 and TMPRSS2 in oral mucosal tissues. Transcriptomic sequencing data of several datasets were then collected to analysis the relationship between the expressions of ACE2 and TMPRSS2 with the age and gender of patients. Furthermore, oral tissues from patients with different ages and genders were collected. Immunohistochemistry staining, qRT-PCR and western blot were performed to explore the relationship between expression levels of ACE2 and TMPRSS2 and patient age as well as gender. Results The results showed that the two proteins were able to be co-expressed in the epithelial cells of oral tissues, and their expression levels were higher in the relatively elderly group than those in relatively younger group. Male oral epithelial cells exhibited higher level of TMPRSS2. Conclusions Our findings comprehensively confirmed the existence of ACE2 and TMPRSS2 in oral tissues and clarify the relationship between the expression levels with human age and gender for the first time, providing evidence for possible entry routes of SARS-CoV-2 and the influencing factors of SARS-CoV-2 colonization in oral cavity. Thus, the oral mucosa might be at potential risk of infection by SARS-CoV-2, especially in male or elderly patients. Using saliva to detect the nucleic acids of SARS-CoV-2 may be more accurate for elder male COVID-19 patients.

Insufficient bone matrix formation caused by diabetic chronic inflammation can result in bone nonunion, which is perceived as a worldwide epidemic, with a substantial socioeconomic and public health burden. Macrophages in microenvironment orchestrate the inflammation and launch the process of bone remodeling and repair, but aberrant activation of macrophages can drive drastic inflammatory responses during diabetic bone regeneration. In diabetes mellitus, the proliferation of resident macrophages in bone microenvironment is limited, while enhanced myeloid differentiation of hematopoietic stem cells (HSCs) leads to increased and constant monocyte recruitment and thus macrophages shift toward the classic pro-inflammatory phenotype, which leads to the deficiency of bone regeneration. In this review, we systematically summarized the anomalous origin of macrophages under diabetic conditions. Moreover, we evaluated the deficit of pro-regeneration macrophages in the diabetic inflammatory microenvironment. Finally, we further discussed the latest developments on strategies based on targeting macrophages to promote diabetic bone regeneration. Briefly, this review aimed to provide a basis for modulating the biological functions of macrophages to accelerate bone regeneration and rescue diabetic fracture healing in the future.

Exposure to artificial light at night (LAN) can induce obesity, depressive disorder and osteoporosis, but the pernicious effects of excessive LAN exposure on tissue structure are poorly understood. Here, we demonstrated that artificial LAN can impair developmental growth plate cartilage extracellular matrix (ECM) formation and cause endoplasmic reticulum (ER) dilation, which in turn compromises bone formation. Excessive LAN exposure induces downregulation of the core circadian clock protein BMAL1, which leads to collagen accumulation in the ER. Further investigations suggest that BMAL1 is the direct transcriptional activator of prolyl 4-hydroxylase subunit alpha 1 (P4ha1) in chondrocytes, which orchestrates collagen prolyl hydroxylation and secretion. BMAL1 downregulation induced by LAN markedly inhibits proline hydroxylation and transport of collagen from ER to golgi, thereby inducing ER stress in chondrocytes. Restoration of BMAL1/P4HA1 signaling can effectively rescue the dysregulation of cartilage formation within the developmental growth plate induced by artificial LAN exposure. In summary, our investigations suggested that LAN is a significant risk factor in bone growth and development, and a proposed novel strategy targeting enhancement of BMAL1-mediated collagen hydroxylation could be a potential therapeutic approach to facilitate bone growth.

Progesterone (P4) is an important biomarker of various diseases. When P4 level exceeds the normal value, the human body produces a series of problems, including carcinogenic risks. Developing the method for P4 monitoring with accurate, inexpensive, and fast becomes an important topic for researchers. In recent years, the abundance of new materials and synthesis technologies has developed P4 biosensors. Based on functional materials, this paper reviews the recent decade literatures and summarizes the latest progress and applications in enhancing detection of P4. In this study, the functional materials used to manufacture P4 biosensors are mainly divided into three categories: metal and metal-oxide nanomaterials, composite material, and other materials. A composite material refers to a combination of two or three types of materials, including carbonaceous nanomaterials, metal nanomaterials, polymers, and biological materials. The other materials mainly include a combination of special compounds, biomaterials, luciferin materials, and quantum dot materials, of which one or two. The introduction of these new functional materials improves the sensitivity and selectivity of P4 detection. Moreover, this study provides ideas for the future research on improving the performance of P4 biosensor. The future study should put more attentions on enzyme catalysis amplification, cyclic amplification, and DNA isothermal amplification strategies.

The occurrence of aging is intricately associated with alterations in circadian rhythms that coincide with stem cell exhaustion. Nonetheless, the extent to which the circadian system governs skeletal aging remains inadequately understood. Here, we noticed that skeletal aging in male mice was accompanied by a decline in a core circadian protein, BMAL1, especially in bone marrow endothelial cells (ECs). Using male mice with endothelial KO of aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), we ascertained that endothelial BMAL1 in bone played a crucial role in ensuring the stability of an extracellular structural component, fibrillin-1 (FBN1), through regulation of the equilibrium between the extracellular matrix (ECM) proteases thrombospondin type 1 domain-containing protein 4 (THSD4) and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), which promote FBN1 assembly and breakdown, respectively. The decline of endothelial BMAL1 during aging prompted excessive breakdown of FBN1, leading to persistent activation of TGF-β/SMAD3 signaling and exhaustion of bone marrow mesenchymal stem cells. Meanwhile, the free TGF-β could promote osteoclast formation. Further analysis revealed that activation of ADAMTS4 in ECs lacking BMAL1 was stimulated by TGF-β/SMAD3 signaling through an ECM-positive feedback mechanism, whereas THSD4 was under direct transcriptional control by endothelial BMAL1. Our investigation has elucidated the etiology of bone aging in male mice by defining the role of ECs in upholding the equilibrium within the ECM, consequently coordinating osteogenic and osteoclastic activities and retarding skeletal aging.

Background Parenting styles play a critical role in children’s development, especially for those in families with a depressed parent. To date, no study has explored whether youth perceptions of parenting style are heterogeneous in families with a depressed parent or whether heterogeneous parenting styles are associated with children’s internalizing symptoms. Methods Participants were children aged 8–16 years who had a parent with major depressive disorder; they were enrolled through their parents, who were outpatients at two hospitals in Ningxia. Parenting styles were measured using the Parental Bonding Instrument. Youth depression and anxiety were measured using the Depression Self-Rating Scale for Children and the Screen for Child Anxiety-Related Emotional Disorders, respectively. We applied latent profile analysis to identify the subtypes of parenting styles with similar patterns. Differences between subtypes in relation to demographic variables and parenting style scores were calculated using one-way ANOVAs, Wilcoxon rank sum tests, and chi-squared tests. Bivariate logistic analyses were conducted to examine the associations between parental bonding subtypes and children’s depression and anxiety. Results Four parenting styles were identified through latent profile analysis: care-autonomy, overprotection-indifference, indifference, and undifferentiated parenting. Youth with care-autonomy parents had a lower risk of depression (OR: 0.16; 95% CI: 0.06–0.41) and anxiety (OR: 0.22; 95% CI: 0.10–0.48), while indifference parenting increased children’s risk of depression (OR: 5.29; 95% CI: 1.30–21.54) more than undifferentiated parenting. Conclusions Children with a depressed parent had heterogeneous perceptions of parenting styles. Mothers’ and fathers’ parenting styles were largely congruent. Care-autonomy parenting (high care and high autonomy) may decrease children’s risk of depression, whereas indifference parenting (low care and autonomy) may increase their risk of depression.

Laizhou Bay’s coastline has undergone multiple alterations due to human activities such as land reclamation and port construction. These changes in the coastline have led to modifications in the bay’s hydrodynamic conditions, which, in turn, can impact the marine environment and potentially result in a decline in biodiversity. To date, there has been no comprehensive study focusing on the coastline changes and hydrodynamic variations in Laizhou Bay. Therefore, this study utilizes coastline and water depth data from four time points—1990, 2003, 2013, and 2023—to establish a two-dimensional tidal current model of Laizhou Bay using Delft3D. Based on the good agreement between the simulated tidal current results and the observed data, this study further investigates the changes in tidal prism and water exchange in Laizhou Bay. The results indicate that tidal currents dominate the bay, with significant influences of topographic changes on the velocity and direction of tidal flows. The Eulerian residual current velocity is substantially lower than the tidal current velocity. Both tidal and residual currents play a role in controlling the distribution of materials within Laizhou Bay. Over the past three decades (1990-2023), the tidal prism in Laizhou Bay has shown a downward trend, with the tidal prism during spring, intermediate, and neap tides in 2023 reduced by 2.03%, 6.36%, and 10.19%, respectively, compared to 1990. The water exchange capacity has also weakened, with the half-exchange time being 71 days in 1990, increasing to 73 days in 2003 and 81 days in 2013, and showing a slight increase of 1 day in 2023 compared to 2013. Thus, changes in the coastline and water depth of Laizhou Bay can alter its hydrodynamic conditions, significantly impacting the tidal prism and water exchange, leading to a decrease in tidal prism and exchange rate, an increase in the water exchange period, a slower dispersion rate of pollutants, and a reduced water environmental carrying capacity. This research provides a scientific reference for protecting the marine environment and coastal management in Laizhou Bay.