Histone lactylation dynamics: Unlocking the triad of metabolism, epigenetics, and immune regulation in metastatic cascade of pancreatic cancer.

Cancer cells rewire metabolism to sculpt the immune tumor microenvironment (TME) and propel tumor advancement, which intricately tied to post-translational modifications. Histone lactylation has emerged as a novel player in modulating protein functions, whereas little is known about its pathological role in pancreatic ductal adenocarcinoma (PDAC) progression. Employing a multi-omics approach encompassing bulk and single-cell RNA sequencing, metabolomics, ATAC-seq, and CUT&Tag methodologies, we unveiled the potential of histone lactylation in prognostic prediction, patient stratification and TME characterization. Notably, "LDHA-H4K12la-immuno-genes" axis has introduced a novel node into the regulatory framework of "metabolism-epigenetics-immunity," shedding new light on the landscape of PDAC progression. Furthermore, the heightened interplay between cancer cells and immune counterparts via Nectin-2 in liver metastasis with elevated HLS unraveled a positive feedback loop in driving immune evasion. Simultaneously, immune cells exhibited altered HLS and autonomous functionality across the metastatic cascade. Consequently, the exploration of innovative combination strategies targeting the metabolism-epigenetics-immunity axis holds promise in curbing distant metastasis and improving survival prospects for individuals grappling with challenges of PDAC.

Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies.

Osteoarthritis (OA) is the most common chronic degenerative joint disease in middle-aged and elderly people, characterized by joint pain and dysfunction. Macrophages are key players in OA pathology, and their activation state has been studied extensively. Various studies have suggested that macrophages might respond to stimuli in their microenvironment by changing their phenotypes to pro-inflammatory or anti-inflammatory phenotypes, which is called macrophage polarization. Macrophages accumulate and become polarized (M1 or M2) in many tissues, such as synovium, adipose tissue, bone marrow, and bone mesenchymal tissues in joints, while resident macrophages as well as other stromal cells, including fibroblasts, chondrocytes, and osteoblasts, form the joint and function as an integrated unit. In this study, we focus exclusively on synovial macrophages, adipose tissue macrophages, and osteoclasts, to investigate their roles in the development of OA. We review recent key findings related to macrophage polarization and OA, including pathogenesis, molecular pathways, and therapeutics. We summarize several signaling pathways in macrophage reprogramming related to OA, including NF-κB, MAPK, TGF-ß, JAK/STAT, PI3K/Akt/mTOR, and NLRP3. Of note, despite the increasing availability of treatments for osteoarthritis, like intra-articular injections, surgery, and cellular therapy, the demand for more effective clinical therapies has remained steady. Therefore, we also describe the current prospective therapeutic methods that deem macrophage polarization to be a therapeutic target, including physical stimulus, chemical compounds, and biological molecules, to enhance cartilage repair and alleviate the progression of OA.

Preschoolers' screen time in China before and during COVID-19 lockdown: a parental survey.

OBJECTIVES: Since COVID-19 first appeared in Wuhan, China, in December 2019, the disease has spread rapidly across the country. To reduce the spread of infection, schools including kindergartens were closed. Prolonged home confinement can affect children's behaviour. Therefore, we investigated the change of preschoolers' total daily screen time during the COVID-19 lockdown in China. DESIGN, SETTING AND PARTICIPANTS: In the parental survey, 1121 preschoolers, whose parents or grandparents completed an online survey from 1 June 2020 to 5 June 2020, were enrolled. PRIMARY OUTCOME: Total daily screen time. Multivariable modelling was performed to identify factors associated with increased screen time. RESULTS: The results showed that preschoolers' total daily screen time during lockdown(median 2.5 hours, IQR 2.5 hours) was significantly longer than it was before lockdown (median 1.5 hours, IQR 1.0 hour). Older age (OR 1.26, 95% CI 1.07 to 1.48), higher annual household income (OR 1.18, 95% CI 1.04 to 1.34),and decrease of moderate-vigorous physical activity (OR 1.41, 95% CI 1.20 to 1.66) were independently associated with increased screen time. CONCLUSIONS: Preschoolers' total daily screen time significantly increased during lockdown.

CircRNAs in lung cancer- role and clinical application.

Lung cancer holds the highest mortality rate among malignancies worldwide. Nevertheless, the potential molecular mechanisms of its tumorigenesis and evolution remain obscure. Circular RNAs (circRNAs), a broad category of covalently closed molecules, follow a malignancy-restricted expression pattern. Leading-edge studies have demonstrated the clinical application prospects of circRNAs in lung cancer. Herein, this review elucidates the biogenesis, biological functions, and pathophysiology of circRNAs. Furthermore, we underscore the forefront of the diagnostic, prognostic, and therapeutic potential of circRNAs in lung cancer as well as discuss the bottleneck that needs to be overcome to translate the basic advances of circRNAs into clinical practice.

[Pleomorphic adenoma of nose and accessory nasal sinuses: a report of 15 cases].

OBJECTIVE: To discuss the clinical characteristics and the treatment of pleomorphic adenoma of nose and accessory nasal sinuses (NPA). METHOD: Fifteen cases of NPA were treated, 2 cases underwent radical maxillary sinusotomy, 2 cases nasal polypectomy, 10 cases lateral rhinotomy and 1 case maxillectomy. RESULT: No recurrence occurred in 7 cases, recurrence occurred in 6 cases, planted recurrence occurred in 1 case, malignant evolution occurred in 1 cases (carcinosarcoma) after the first operation. The 6 cases of recurrence underwent an operation for the second time, 2 cases had no recurrence, 2 cases recurred again, 2 cases became malignant (one was adenoid cystic carcinoma, the other was squamous cell carcinoma). The case who was planted recurrence underwent radiotherapy with 60 Gy and died of failure to respond to medical treatment at last. CONCLUSION: The rate of recurrence and misdiagnosis is very high in NPA, this tumor can be malignant evolution easily after many operations. To get rid of focus completely, it is important to apply a wide range of surgical operation in the first operation, which is the key to treatment. Rapid sections-cutting for microscopic examination should be done during operation, biopsy must not be done before operation if a tumour of nose is suspected to be NPA. Prognosis of this tumour is mainly linked to recurrences in cases of incomplete resection and to possible metastasis, such as an eventual malignant evolution.

Synthesis of ordered mesoporous carbon monoliths with bicontinuous cubic pore structure of Ia3d symmetry.

Large-diameter-sized mesoporous carbon monoliths with bicontinuous cubic structure of Ia3d symmetry have been synthesized by using mesoporous silica monoliths as hard templates; such carbon monoliths show potential application of advanced electrodes and electrochemical double layer capacitors.