Interaction between CAFs and apoptotic cancer cells promotes OSCC proliferation via STING signaling.

BACKGROUND: Apoptosis can fuel oncogenesis by the education of surrounding stromal cells. However, the function of cancer-associated fibroblasts (CAFs), which interacted with apoptotic cancer cells, in oral squamous cell carcinoma (OSCC) progression is still unknown. OBJECTIVES: This study aimed to explore the prognostic value of apoptosis and the biological effects of CAFs, interacted with apoptotic cancer cells, on OSCC. METHODS: A total of 166 samples from OSCC patients were stained via TUNEL reaction to evaluate the correlation between apoptosis and clinical characteristics. Cell viability and proliferation were assessed through flow cytometry and CCK-8 assays, respectively. Levels of mRNA and protein were examined through qRT-PCR, western blot and immunofluorescence. RESULTS: Higher percentage of apoptotic cancer cells in OSCC positively correlated with more Ki67+ cells and predicted poor clinical outcomes. Conditioned medium from CAFs exposed to apoptotic cancer cells significantly facilitated cell proliferation. Co-culture CAFs with apoptotic cancer cells dampened the phosphorylation of STING/IRF3 signaling, as well as the production of type I interferon, which was required for the inhibition of OSCC cell proliferation. CONCLUSION: These results demonstrate the interplay between apoptotic cancer cells and CAFs promotes OSCC proliferation via STING signaling, identifying a potential therapy targeted CAFs surrounded with apoptotic cancer cells for OSCC.

Circ6834 suppresses non-small cell lung cancer progression by destabilizing ANHAK and regulating miR-873-5p/TXNIP axis.

BACKGROUND: Circular RNAs (circRNAs) play important roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear. METHODS: In this study, we identified a novel circRNA, hsa_circ_0006834 (termed circ6834), in NSCLC by RNA-seq and investigated the biological role of circ6834 in NSCLC progression in vitro and in vivo. Finally, the molecular mechanism of circ6834 was revealed by tagged RNA affinity purification (TRAP), western blot, RNA immunoprecipitation, dual luciferase reporter gene assays and rescue experiments. RESULTS: Our results showed that circ6834 was downregulated in NSCLC tumor tissues and cell lines. Circ6834 overexpression inhibited NSCLC cell growth and metastasis both in vitro and in vivo, while circ6834 knockdown had the opposite effect. We found that TGF-ß treatment decreased circ6834 expression, which was associated with the QKI reduction in NSCLC cells and circ6834 antagonized TGF-ß-induced EMT and metastasis in NSCLC cells. Mechanistically, circ6834 bound to AHNAK protein, a key regulator of TGF-ß/Smad signaling, and inhibited its stability by enhancing TRIM25-mediated ubiquitination and degradation. In addition, circ6834 acted as a miRNA sponge for miR-873-5p and upregulated TXNIP gene expression, which together inactivated the TGF-ß/Smad signaling pathway in NSCLC cells. CONCLUSION: In conclusion, circ6834 is a tumor-suppressive circRNA that inhibits NSCLC progression by forming a negative regulatory feedback loop with the TGF-ß/Smad signaling pathway and represents a novel therapeutic target for NSCLC.

Global area boom for greenhouse cultivation revealed by satellite mapping.

Greenhouse cultivation has been expanding rapidly in recent years, yet little knowledge exists on its global extent and expansion. Using commercial and freely available satellite data combined with artificial intelligence techniques, we present a global assessment of greenhouse cultivation coverage and map 1.3 million hectares of greenhouse infrastructures in 2019, a much larger extent than previously estimated. Our analysis includes both large (61%) and small-scale (39%) greenhouse infrastructures. Examining the temporal development of the 65 largest clusters (>1,500 ha), we show a recent upsurge in greenhouse cultivation in the Global South since the 2000s, including a dramatic increase in China, accounting for 60% of the global coverage. We emphasize the potential of greenhouse infrastructures to enhance food security but raise awareness of the uncertain environmental and social implications that may arise from this expansion. We further highlight the gap in spatio-temporal datasets for supporting future research agendas on this critical topic.

Unique Approach for Isolating Rat Bone Marrow Neutrophils with Comparable Capacity.

The primary aim of this research was to develop a reliable and efficient approach for isolating neutrophil extracellular traps (NETs) from rat bone marrow. This effort arose due to limitations associated with the traditional method of extracting NETs from peripheral blood, mainly due to the scarcity of available neutrophils for isolation. The study revealed two distinct methodologies for obtaining rat neutrophils from bone marrow: a streamlined one-step procedure that yielded satisfactory purification levels, and a more time-intensive two-step process that exhibited enhanced purification efficiency. Importantly, both techniques yielded a substantial quantity of viable neutrophils, ranging between 50 to 100 million per rat. This efficiency mirrored the results obtained from isolating neutrophils from both human and murine sources. Significantly, neutrophils derived from rat bone marrow exhibited comparable abilities to secrete NETs when compared with neutrophils obtained from peripheral blood. However, the bone marrow-based method consistently produced notably larger quantities of both neutrophils and NETs. This approach demonstrated the potential to obtain significantly greater amounts of these cellular components for further downstream applications. Notably, these isolated NETs and neutrophils hold promise for a range of applications, spanning the realms of inflammation, infection, and autoimmune diseases.

M2 Tumor-Associated Macrophages-Derived Exosomal MALAT1 Promotes Glycolysis and Gastric Cancer Progression.

M2-polarized tumor-associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs-derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis-dependent manner. It is identified that MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ-catenin protein and suppressed its ubiquitination and degradation by ß-TRCP. In addition, MALAT1 upregulated HIF-1α expression by acting as a sponge for miR-217-5p. The activation of ß-catenin and HIF-1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome-mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs-derived exosomes promote gastric cancer progression via MALAT1-mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma.

BACKGROUND: Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC). METHODS: PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis. RESULTS: Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3high tumor showed high proliferation index with metastasis potential, accompanied with less CD3+CD8+ T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8+ T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3highB7-H2high tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285-6.851). CONCLUSIONS: LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.

Neonicotinoid insecticides in waters of the northern Jiangsu segment of the Beijing-Hangzhou Grand Canal: Environmental and health implications.

Neonicotinoid (NEO) insecticides have been frequently detected in natural aquatic environments. Nevertheless, the distribution of NEOs in artificial environments is not clear. The Beijing-Hangzhou Grand Canal is the longest canal in the world. The northern Jiangsu segment of the Grand Canal was selected to study the spatiotemporal variation and source of eight NEOs in the canal water and assess their ecological and health risks. The total NEO concentration in the canal water was 12-289 ng L-1 in the dry season and 18-373 ng L-1 in the wet season, which were within the concentration range in other 11 natural rivers worldwide. The average total NEO concentrations were not statistically different between the seasons; only the concentrations of imidaclothiz, thiacloprid (THI), acetamiprid, and dinotefuran were different. At city scale, the total NEO concentration in the dry season showed a decreasing trend along the water flow from Xuzhou City to Yangzhou City. The total NEO concentrations were found to be positively correlated with the sown area of farm crops and the rural labour force, indicating the agricultural influence on the spatial distribution of NEO concentrations. In the wet season, relatively high NEO concentrations were distributed in downstream sites under the influence of artificial regulation. The primary contributor to the NEO inputs into the canal was the nonpoint source in the dry and wet seasons, with a relative contribution of 68 %. THI, imidacloprid, clothianidin and thiamethoxan would produce chronic ecological risks in both seasons. Further consideration needs to be given to the above four NEOs and NEO mixtures. The human health risks that NEOs posed by drinking water were assessed based on the chronic daily intake (CDI). The maximum CDI for adults and children was lower than the reference doses. This suggested public health would not be at risk from canal water consumption.

Tailored Exfoliation of Polymeric Carbon Nitride for Photocatalytic H2O2 Production and CH4 Valorization Mediated by O2 Activation.

The exfoliation of bulk C3N4 (BCN) into ultrathin layered structure is an effective strategy to boost photocatalytic efficiency by exposing interior active sites and accelerating charge separation and transportation. Herein, we report a novel nitrate anion intercalation-decomposition (NID) strategy that is effective in peeling off BCN into few-layer C3N4 (fl-CN) with tailored thickness down to bi-layer. This strategy only involves hydrothermal treatment of BCN in diluted HNO3 aqueous solution, followed by pyrolysis at various temperatures. The decomposition of the nitrate anions not only exfoliates BCN and changes the band structure, but also incorporates oxygen species onto fl-CN, which is conducive to O2 adsorption and hence relevant chemical processes. In photocatalytic O2 reduction under visible light irradiation, the H2O2 production rate over the optimal fl-CN-530 catalyst is 952 µmol g-1 h-1, which is 8.8 times that over BCN. More importantly, under full arc irradiation and in the absence of hole scavenger, CH4 can be photocatalytically oxidized by on-site formed H2O2 and active oxygen species to generate value-added C1 oxygenates with high selectivity of 99.2 % and record-high production rate of 1893 µmol g-1 h-1 among the metal-free C3N4-based photocatalysts.

Development of a super-hydrophilic anaerobic tube for the optimization of platelet-rich fibrin.

Horizontal platelet-rich fibrin (H-PRF) contains a variety of bioactive growth factors and cytokines that play a key role in the process of tissue healing and regeneration. The blood collection tubes used to produce Solid-PRF (plasmatrix (PM) tubes) have previously been shown to have a great impact on the morphology, strength and composition of the final H-PRF clot. Therefore, modification to PM tubes is an important step toward the future optimization of PRF. To this end, we innovatively modified the inner wall surface of the PM tubes with plasma and adjusted the gas environment inside the PM tubes to prepare super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes). It was made anaerobic for the preparation of H-PRF with the aim of improving mechanical strength and bioactivity. The findings demonstrated that an anaerobic environment stimulated platelet activation within the PRF tubes. After compression, the prepared H-PRF membrane formed a fibrous cross-linked network with high fracture strength, ideal degradation characteristics, in addition to a significant increase in size. Thereafter, the H-PRF membranes prepared by the SHAP tubes significantly promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts while maintaining excellent biocompatibility, and advantageous antibacterial properties. In conclusion, the newly modified PRF tubes had better platelet activation properties leading to better mechanical strength, a longer degradation period, and better regenerative properties in oral cell types including gingival fibroblast and alveolar osteoblasts. It also improves the success rate of H-PRF preparation in patients with coagulation dysfunction and expands the clinical application scenario.

Why was the study done?   Direct anaerobic environment effects on fibrin formation have been insufficiently studied.The effect of hydrophilic change caused by nitrogen plasma treatment on H-PRF coagulation has not been fully studied.Optimal preparation of H-PRF in patients with poor coagulation function was needed in clinical application.What is new?  The coagulation of H-PRF correlated with the level of dissolved oxygen concentrations. Anaerobic environment significantly accelerates fibrin formation and platelet activation.Nitrogen plasma treatment can remarkably enhance the hydrophilicity of the inner surface of glass blood collecting tubes, thereby promoting the activation of platelets and the formation of fibrin network.The H-PRF prepared in the tubes with anaerobic environment and hydrophilic surface showed high fracture strength, promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts.What is the impact?  The work is aimed at developing super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes) for studying gas environment and hydrophilicity participation in fibrin formation in H-PRF preparation and investigating the influence of platelet activation in the anaerobic environment.This study provides a successful trial to convert the physiological process into biotechnological application. The SHAP tubes proposed within this article was an effective versatile H-PRF preparation device, which provided a promising alternative for tissue engineering.

IL-36 antagonism blunts the proliferation and migration of oral squamous cell carcinoma cells.

IL-36 is known to mediate inflammation and fibrosis. Nevertheless, IL-36 signalling axis has also been implicated in cancer, although understanding of exact contribution of IL-36 to cancer progression is very limited, partly due to existence of multiple IL-36 ligands with agonistic and antagonistic function. Here we explored the role of IL-36 in oral squamous cell carcinoma (OSCC). Firstly, we analyzed expression of IL-36 ligands and receptor and found that the expression of IL-36γ was significantly higher in head and neck cancer (HNSCC) than that of normal tissues, and that the high expression of IL-36γ predicted poor clinical outcomes. Secondly, we investigated the direct effect of IL-36γ on OSCC cells and found that IL-36γ stimulated proliferation of OSCC cells with high expression of IL-36R expression. Interestingly, IL-36γ also promoted migration of OSCC cells with low to high IL-36R expression. Critically, both proliferation and migration of OSCC cells induced by IL-36γ were abrogated by anti-IL-36R mAb. Fittingly, RNA sequence analysis revealed that IL-36γ regulated genes involved in cell cycle and cell division. In summary, our results showed that IL-36γ can be a tumor-promoting factor, and targeting of IL-36R signalling may be a beneficial targeted therapy for patients with abnormal IL-36 signalling.

Decidual stromal cells-derived exosomes incurred insufficient migration and invasion of trophoblast by disturbing of ß-TrCP-mediated snail ubiquitination and degradation in unexplained recurrent spontaneous abortion.

BACKGROUND: Exosomes released from decidual stromal cells (DSC-exos) play a crucial role in facilitating the epithelial-mesenchymal transition (EMT) of trophoblasts and insufficient trophoblasts EMT are associated with URSA (unexplained recurrent spontaneous abortion). However, the mechanisms underlying DSC-exos inducing EMT is not completely understood. METHODS: DSC-exos of normal pregnant women (N-DSC-exos) and URSA patients (URSA-DSC-exos) were extracted and characterized. Characterization of the isolated DSC-exos was performed using with TEM (transmission electron microscopy), NTA (nanoparticle tracking analysis), and WB (western blot) techniques. Subsequently, these DSC-exos were co-cultured with trophoblasts cell lines (HTR-8/SVneo). The influence of both N-DSC-exos and URSA-DSC-exos on trophoblasts proliferation, invasion and migration, as well as on the expression of EMT-related proteins, was evaluated through a series of assays including CCK8 assays, wound healing assays, transwell assays, and western blot, respectively. Then rescue experiments were performed by ß-TrCP knockdown or ß-TrCP overexpressing trophoblasts with snail-siRNA transfection or ß-TrCP overexpressing Lentivirus infection, respectively. Finally, animal experiments were employed to explore the effect of N-DSC-exos on embryo absorption in mice. RESULTS: We found increased ß-TrCP expression in the villus of URSA patients when compared to the normal pregnant women, alongside reduction in the levels of both snail and N-cadherin within URSA patients. N-DSC-exos can promote the EMT of the trophoblast by inhibiting ß-TrCP-mediated ubiquitination and degradation of transcription factor snail. Moreover the capacity to promote EMT was found to be more potent in N-DSC-exos than URSA-DSC-exos. Down-regulation of snail or overexpression of ß-TrCP can reverse the effects of N-DSC-exos on trophoblast. Finally, in vivo experiment suggested that N-DSC-exos significantly reduced the embryo resorption rate of spontaneous abortion mouse model. CONCLUSIONS: Our findings indicate that URSA-DSC-exos caused insufficient migration and invasion of trophoblast because of disturbing of ß-TrCP-mediated ubiquitination and degradation of EMT transcription factor snail. Elucidating the underlying mechanism of this dysregulation may shed light on the novel pathways through which DSC-exos influence trophoblast function, thereby contributing to our understanding of their role in URSA.

Application of the plasmatrix in alveolar ridge preservation / 口腔疾病防治

@#After tooth extraction, significant absorption occurs in the soft and hard tissues of the alveolar ridge. The goal of alveolar ridge preservation is to maintain the volume and shape of the alveolar ridge's soft and hard tissues as much as possible so as to provide suitable conditions for implant placement. Currently, there are challenges in classifying the socket for alveolar ridge preservation, such as the difficulty in directly guiding the selection of graft materials and clinical procedures and the insufficient space for particle xenograft maintenance, resulting in poor bone regeneration. Plasmatrix is an autologous blood derivative that effectively enhances tissue regeneration. This article introduced the characteristics of soft and hard tissue defects after tooth extraction and the primary applications of plasmatrix for alveolar ridge preservation (liquid plasmatrix, solid plasmatrix membrane/plug, and plasmatrix bone blocks) as well as the proposed methods for the reclassification of sockets for alveolar ridge preservation based on soft and hard tissue defects at the extraction site to facilitate the creation of clinical recommendations. The proposed classifications are as follows: Class I, extraction socket without bone defect, with or without soft tissue defect; Class Ⅱ, extraction socket with bone defect, both sides with bone wall defect less than 50%, with or without soft tissue defect; Class Ⅲ, extraction socket with bone tissue defect, at least one side with bone wall defect greater than 50%, with or without soft tissue defect. For the Class I socket, a solid plasmatrix membrane or plug is inserted, followed by injection of liquid plasmatrix, using a double-layer solid plasmatrix membrane for socket closure; for the ClassⅡ socket, plasmatrix bone blocks are inserted, followed by injection of liquid plasmatrix and secondary solidification, using absorbable collagen membrane and double-layer solid plasmatrix membrane for socket closure; for the ClassⅢ socket, tenting screws are used to maintain height, followed by implantation of plasmatrix bone blocks, injection of liquid plasmatrix and secondary solidification, using absorbable collagen membrane and double-layer solid plasmatrix membrane for socket closure. The aim of this article is to provide comprehensive knowledge of plasmatrix for oral clinicians to serve as a reference to simplify the clinical decision-making process and procedures for alveolar ridge preservation.

Cardiac rehabilitation for elderly, weak patients who undergo transcatheter edge-to-edge repair: a case report.

Background: The positive role of rehabilitation programmes for some cardiac patient populations (e.g. coronary artery disease, heart failure, transcatheter aortic valve replacement, and heart transplantation) is now well-known. However, the feasibility and outcomes of rehabilitation, prior to or immediately after percutaneous mitral valve reconstruction, using a clamping procedure have been poorly reported, especially among frail elderly patients. Case summary: An 85-year-old woman with acute heart failure symptoms (New York Heart Association functional class III), who had acute myocardial infarction 3 months ago, was hospitalized. An ultrasound cardiogram showed severe mitral regurgitation, and after a multidisciplinary discussion, transcatheter edge-to-edge repair (TEER) was considered the safest treatment option. Even then, though, due to her poor health status, it was still too risky for the patient to undergo without significant prior preparation. Thus, we decided to begin pre- and post-surgery cardiac rehabilitation (CR) to prepare her for TEER, comprising medicinal, nutritional, and psychological support, as well as exercise and smoking cessation. After pre-operative assessment and rehabilitation, the patient underwent TEER, followed by post-operative reassessment, and continued rehabilitation. Discussion: Our case study demonstrates that CR, both pre- and post-TEER, aids in improving the conditions of elderly patients with poor health, to minimize their risk for developing TEER-related complications. This case provides one possible CR regimen for those patients.

Effect of thermal manipulation on the biological and mechanical characteristics of horizontal platelet rich fibrin membranes.

BACKGROUD: Regardless of application scenarios, proper mechanical characteristics and degradation properties are prerequisites for horizontal platelet rich fibrin (H-PRF) to manifest its ability. Among the methods used to modify PRF, thermal manipulation is promising as it is easy to handle without adding extra additives. Yet there is no consensus on optimal temperature treatment. This study aimed to investigate the effects of heating on the biological and mechanical characteristics of H-PRF and explore the optimum heating temperature for H-PRF thermal treatment. METHODS: We employed a series of temperature gradients, room temperature, 50℃, 75℃, 90℃, 105℃. The microstructure and the mechanical properties were recorded by Scanning Electron Microscope (SEM) and tensile strength tests respectively. The degradation rate of H-PRF membranes was examined by digestion assay with plasmin and trypsin. The viability of cells within H-PRF membranes and the proliferation of osteoblasts cultured with extracts from different H-PRF groups was evaluated using CCK-8 assays. RESULTS: Compared with the nonheated group, overheated manipulation beyond 90℃ can significantly prolong the degradation properties for up to 3 to 4 weeks and enhance the mass stress of H-PRF membranes. A high-temperature treatment of 105℃ accompanied by the cell activity beneath H-PRF reduced more than half, and thus, the biological effect on human osteoblasts (hFOBs) also reduced dramatically. CONCLUSIONS: High thermal manipulation can prolong the degradation properties and enhance the mechanical properties of PRF membranes accompanied by the loss of biological effect.

Biomedical application of terahertz imaging technology: a narrative review.

Background and Objective: Terahertz (THz) imaging has wide applications in biomedical research due to its properties, such as non-ionizing, non-invasive and distinctive spectral fingerprints. Over the past 6 years, the application of THz imaging in tumor tissue has made encouraging progress. However, due to the strong absorption of THz by water, the large size, high cost, and low sensitivity of THz devices, it is still difficult to be widely used in clinical practice. This paper provides ideas for researchers and promotes the development of THz imaging in clinical research. Methods: The literature search was conducted in the Web of Science and PubMed databases using the keywords "Terahertz imaging", "Breast", "Brain", "Skin" and "Cancer". A total of 94 English language articles from 1 January, 2017 to 30 December, 2022 were reviewed. Key Content and Findings: In this review, we briefly introduced the recent advances in THz near-field imaging, single-pixel imaging and real-time imaging, the applications of THz imaging for detecting breast, brain and skin tissues in the last 6 years were reviewed, and the advantages and existing challenges were identified. It is necessary to combine machine learning and metamaterials to develop real-time THz devices with small size, low cost and high sensitivity that can be widely used in clinical practice. More powerful THz detectors can be developed by combining graphene, designing structures and other methods to improve the sensitivity of the devices and obtain more accurate information. Establishing a THz database is one of the important methods to improve the repeatability and accuracy of imaging results. Conclusions: THz technology is an effective method for tumor imaging. We believe that with the joint efforts of researchers and clinicians, accurate, real-time, and safe THz imaging will be widely applied in clinical practice in the future.

Liquid platelet-rich fibrin produced via horizontal centrifugation decreases the inflammatory response and promotes chondrocyte regeneration in vitro.

Objective: Recently, liquid platelet-rich fibrin (PRF), a rich source of concentrated platelets and growth factors, has emerged as a promising agent for stimulating tissue regeneration. However, its specific efficacy in chondrocyte proliferation and cartilage regeneration remains underexplored. To address this question, we investigated liquid PRF obtained through horizontal centrifugation and compared its effects with hyaluronic acid (HA), a high molecular weight glucosamine supplement widely used in clinical practice to safeguard against chondral damage. Materials and Methods: Liquid PRF, produced using horizontal centrifugation (liquid H-PRF) at 500 g for 8 min, served as our experimental agent. We conducted cell viability and proliferation assays using PRF-conditioned medium. We assessed the chondrocyte phenotype of ATDC5 cells through toluidine blue and alcian blue staining, real-time polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence staining. Furthermore, we examined the expression of genes involved in inflammation through RT-PCR and Western blot analysis. Results: Liquid H-PRF exerted notable effects on chondrocytes, influencing proliferation, inflammatory responses, and chondrogenic differentiation. The H-PRF group displayed significantly higher expression of chondrogenic markers, including Col2a1, compared to HA-treated cells, whereas aggrecan expression was significantly higher in the HA group. PRF also demonstrated the ability to reduce inflammatory levels in chondrogenic ATDC5 cells, and this effect was further enhanced when PRF from the buffy coat zone was added. In comparison, chondrocytes cultured in the HA group produced significantly fewer inflammatory factors than those in the PRF group, as confirmed qualitatively by Western blot analysis. Conclusion: Liquid H-PRF emerged as a potent stimulator for chondrogenesis and a regulator of the inflammatory response, achieving levels similar to HA. Moreover, liquid H-PRF exhibited strong potential for enhancing the production of cartilage extracellular matrix and promoting chondrogenic regeneration with notably increased Col2a1 levels. Future research should encompass animal studies and human trials to further evaluate the comparative effectiveness of liquid PRF versus HA, potentially as an alternative or complementary strategy for future clinical applications.

IGF2BP2-meidated m6A modification of CSF2 reprograms MSC to promote gastric cancer progression.

The interaction between tumor cells and stromal cells within the tumor microenvironment plays a critical role in cancer progression. Mesenchymal stem cells (MSCs) are important tumor stromal cells that exhibit pro-oncogenic activities when reprogrammed by the tumor. However, the precise mechanisms underlying MSC reprogramming in gastric cancer remain not well understood. QRT-PCR, western blot, and immunohistochemistry were used to examine gene and protein expression levels. In vitro and in vivo experiments were conducted to assess the biological functions of gastric cancer cells. RNA-sequencing, RNA immunoprecipitation (RIP), and meRIP assays were performed to investigate underlying molecular mechanisms. We found a significant increase in the expression and N6-methyladenosine (m6A) modification levels of colony-stimulating factor 2 (CSF2) in gastric cancer MSCs. CSF2 gene overexpression induced the reprogramming of normal MSCs into cancer-promoting MSCs, thereby enhancing the proliferation, migration, and drug resistance of gastric cancer cells through the secretion of various pro-inflammatory factors. Additionally, we demonstrated that the m6A reader IGF2BP2 bound to and stabilized CSF2 mRNA in gastric cancer MSCs. Notably, overexpression of IGF2BP2 mimicked the effect of CSF2 on MSCs, promoting gastric cancer progression. Finally, we unveiled that CSF2 induced the ubiquitination of Notch1 to reprogram MSCs. Our study highlights a critical role of IGF2BP2-mediated m6A modification of CSF2 in reprogramming MSCs, which presents a promising therapeutic target for gastric cancer.

A high spatial resolution dataset for methylmercury exposure in Guangdong-Hong Kong-Macao Greater Bay Area.

Dietary methylmercury (MeHg) exposure increases the risk of many human diseases. The Guangdong-Hong Kong-Macao Greater Bay Area (GBA) is the world's most populous bay area and people there might suffer a high risk of dietary MeHg exposure. However, there lacks a time-series high spatial resolution dataset for dietary MeHg exposure in the GBA. This study constructs a high spatial resolution (1 km × 1 km) dataset for dietary MeHg exposure in the GBA during 2009-2019. It first constructs the dietary MeHg exposure inventory for each county/district of the GBA, based on MeHg concentrations of foods (i.e., rice and fish in this study) and per capita rice and fish intake. Subsequently, this study spatializes the dietary MeHg exposure inventory at 1 km × 1 km scale, using gridded data for food consumption expenditure as the proxy. This dataset can describe the spatially explicit hotspots, distribution patterns, and variation trend of dietary MeHg exposure in the GBA. This dataset can support spatially explicit evaluation of MeHg-related health risks in the GBA.

LINC02159 promotes non-small cell lung cancer progression via ALYREF/YAP1 signaling.

Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have emerged as key regulators of cancer development and progression, and as promising biomarkers for the diagnosis and prognosis of cancer. In this study, we identified a new lncRNA (LINC02159) that was upregulated in the tumor tissues and serum of non-small cell lung cancer (NSCLC) patients. We demonstrated that knockdown of LINC02159 inhibited NSCLC cell proliferation, migration, and invasion, but induced cell apoptosis and cell cycle arrest in vitro and retarded tumor growth in vivo, while overexpression of LINC02159 led to the opposite effect. We discovered that LINC02159 was highly correlated with cancer growth and metastasis-related pathways by using transcriptomic analysis and that YAP1 was a potential target gene of LINC02159. Mechanistically, LINC02159 bound to the Aly/REF export factor (ALYREF) to enhance the stability of YAP1 messenger RNA (mRNA) via m5C modification, which led to the overexpression of YAP1 and the activation of the Hippo and ß-catenin signaling pathways in NSCLC cells. Rescue experiments showed that LINC01259 promoted NSCLC progression in a YAP1- and ALYREF-dependent manner. In conclusion, LINC02159 plays an oncogenic role in NSCLC progression by regulating ALYREF/YAP1 signaling, and it has the potential to be utilized as a diagnostic marker and therapeutic target for NSCLC.