HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

How do patients' perceptions and doctors' images impact patient decisions? Deconstructing online physician selection using multimodal data.

In the post-pandemic era, medical resources are uneven, and access to healthcare is complicated. Online medical platforms have become a solution to bridge the information gap and reduce hospital pressure. This study uses the stereotype content model and signaling theory to explore the impact of patient perception of patient decision making (PDM) on online medical service platforms. Also, it tests the moderating effect of physician image. We collected information on 12,890 physicians and 746,981 patient reviews from online medical platforms in China. Unsupervised machine learning was used to construct a topic model to extract patients' perceptions of physicians' competence and warmth. Meanwhile, the facial features of physicians, such as age, smile, and glasses, are recognized by convolutional neural networks. Finally, the influence of PDM concern on decision-making and the moderating effect of physician image were analyzed by multiple linear regression. The results of the study showed that (1) patients' perceptions of physicians' competence and warmth had a positive effect on decision-making; (2) physicians' age and wearing glasses enhanced the positive effect of perception on decision-making; and (3) however, physicians' smiles weakened the positive effect of perception on decision-making. This study provides new insights into patients' online physician selection, guides the construction and promotion of medical service platforms, and provides an effective avenue of exploration to alleviate the problem of uneven distribution of offline medical resources.

Risk factors associated with changes in serum anti-Müllerian hormone levels before and after laparoscopic cystectomy for endometrioma.

Background: The objective of our study was to investigate the risk factors for a decrease in ovarian reserve in patients with endometriomas after standardized laparoscopic procedures and evaluation to provide corresponding clinical guidance for patients with fertility requirements. Methods: Anti-Müllerian hormone (AMH) levels and other clinical data from 233 patients with endometriomas and 57 patients with non-endometrioma ovarian cysts admitted to the Peking Union Medical College Hospital between January 2018 and September 2023 were prospectively analysed. The pretreatment AMH levels of the study groups were compared to assess the impact of endometrioma on ovarian reserve, and the decrease in AMH after treatment was analysed to determine potential risk factors contributing to this change. Results: Pretreatment AMH levels did not significantly differ between patients with endometriomas and those with non-endometrioma ovarian cysts. Within the endometrioma group, older age, higher body mass index (BMI), and shorter menstrual cycles were found to be associated with decreased AMH levels prior to treatment (p<0.05). Participants presenting with bilateral cysts, advanced surgical staging, or a completely enclosed Douglas pouch demonstrated significantly lower levels of AMH prior to treatment compared to those without these conditions (p<0.05). Furthermore, their AMH levels further declined within one year after undergoing laparoscopic cystectomy (p<0.05). However, there was no difference in AMH levels after surgery between patients who successfully became pregnant and those who did not (p>0.05). Conclusion: Laparoscopic removal of endometriomas can adversely affect ovarian reserve, especially during bilateral cysts removal and when patients are diagnosed as having a higher stage of endometriosis, further impacting ovarian function. It should be noted that a decrease in AMH levels may not necessarily indicate an absolute decline in fertility. Therefore, it is crucial to conduct thorough patient evaluations and provide comprehensive patient education to offer appropriate guidance for fertility preservation.

Social-economic transitions and vulnerability to extreme temperature events from 1960 to 2020 in Chinese cities.

Climate change leads to more frequent and intense extreme temperature events, causing a significant number of excess deaths. Using an epidemiological approach, we analyze all-cause deaths related to heatwaves and cold spells in 2,852 Chinese counties from 1960 to 2020. Economic losses associated with these events are determined through the value of statistical life. Findings reveal that cold-related cumulative excess deaths (1,133 thousand) are approximately 2.5 times higher than heat-related deaths, despite an increase in heat-related fatalities in recent decades. Monetized mortality due to heat-related events is estimated at 1,284 billion CNY, while cold-related economic loss is 1,510 billion CNY. Notably, cities located in colder regions experience more heat-related excess deaths, and vice versa. Economic development does not significantly reduce mortality risks to heatwaves across China. This study provides insights into the spatial-temporal heterogeneity of heatwaves and cold spells mortality, essential for policymakers ensuring long-term climate adaptation and sustainability.

The pathogenesis of endometriosis and adenomyosis: insights from single-cell RNA sequencing.

Endometriosis and adenomyosis are two similar gynecological diseases that are characterized by ectopic implantation and the growth of the endometrial tissue. Previous studies have reported that they share a common pathophysiology in some respects, such as a similar cellular composition and resistance to the progestogen of lesions, but their underlying mechanisms remain elusive. Emerging single-cell RNA sequencing (scRNA-seq) technologies allow for the dissection of single-cell transcriptome mapping to reveal the etiology of diseases at the level of the individual cell. In this review, we summarized the published findings in research on scRNA-seq regarding the cellular components and molecular profiles of diverse lesions. They show that epithelial cell clusters may be the vital progenitors of endometriosis and adenomyosis. Subclusters of stromal cells, such as endometrial mesenchymal stem cells and fibroblasts, are also involved in the occurrence of endometriosis and adenomyosis, respectively. Moreover, CD8+ T cells, natural killer cells, and macrophages exhibit a deficiency in clearing the ectopic endometrial cells in the immune microenvironment of endometriosis. It seems that the immune responses are activated in adenomyosis. Understanding the immune characteristics of adenomyosis still needs further exploration. Finally, we discuss the application of findings from scRNA-seq for clinical diagnosis and treatment. This review provides fresh insights into the pathogenesis of endometriosis and adenomyosis as well as the therapeutic targets at the cellular level.

HMGA1 drives chemoresistance in esophageal squamous cell carcinoma by suppressing ferroptosis.

Chemotherapy is a primary treatment for esophageal squamous cell carcinoma (ESCC). Resistance to chemotherapeutic drugs is an important hurdle to effective treatment. Understanding the mechanisms underlying chemotherapy resistance in ESCC is an unmet medical need to improve the survival of ESCC. Herein, we demonstrate that ferroptosis triggered by inhibiting high mobility group AT-hook 1 (HMGA1) may provide a novel opportunity to gain an effective therapeutic strategy against chemoresistance in ESCC. HMGA1 is upregulated in ESCC and works as a key driver for cisplatin (DDP) resistance in ESCC by repressing ferroptosis. Inhibition of HMGA1 enhances the sensitivity of ESCC to ferroptosis. With a transcriptome analysis and following-up assays, we demonstrated that HMGA1 upregulates the expression of solute carrier family 7 member 11 (SLC7A11), a key transporter maintaining intracellular glutathione homeostasis and inhibiting the accumulation of malondialdehyde (MDA), thereby suppressing cell ferroptosis. HMGA1 acts as a chromatin remodeling factor promoting the binding of activating transcription factor 4 (ATF4) to the promoter of SLC7A11, and hence enhancing the transcription of SLC7A11 and maintaining the redox balance. We characterized that the enhanced chemosensitivity of ESCC is primarily attributed to the increased susceptibility of ferroptosis resulting from the depletion of HMGA1. Moreover, we utilized syngeneic allograft tumor models and genetically engineered mice of HMGA1 to induce ESCC and validated that depletion of HMGA1 promotes ferroptosis and restores the sensitivity of ESCC to DDP, and hence enhances the therapeutic efficacy. Our finding uncovers a critical role of HMGA1 in the repression of ferroptosis and thus in the establishment of DDP resistance in ESCC, highlighting HMGA1-based rewiring strategies as potential approaches to overcome ESCC chemotherapy resistance. Schematic depicting that HMGA1 maintains intracellular redox homeostasis against ferroptosis by assisting ATF4 to activate SLC7A11 transcription, resulting in ESCC resistance to chemotherapy.

The difference in extracellular matrix metabolism in women with and without pelvic organ prolapse: A systematic review and meta-analysis.

BACKGROUND: Studies on the changes of extracellular matrix (ECM) in pelvic organ prolapse (POP) are still controversial. OBJECTIVE: To identify the changes in the ECM in POP patients. SEARCH STRATEGY: Comprehensive searching in Embase, PubMed, Web of Science and the Cochrane Library was carried out until 23 February 2023. SELECTION CRITERIA: Studies comparing the protein levels of ECM-related components between women with and without POP. DATA COLLECTION AND ANALYSIS: Quality and risk of bias were assessed using the Agency for Healthcare Research and Quality assessment. Indicators were pooled with random or fixed effect meta-analysis based on heterogeneity and sub-grouped analysed by the biopsy site. MAIN RESULTS: Thirty cross-sectional studies were included, comprising 840 POP cases and 755 controls. Overall results showed that the expression of type III collagen (COLIII) and several matrix metalloproteinases (MMP-1, -2 and -9) were increased, whereas those of type I collagen (COLI), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were decreased in patients with POP. Subgroup analysis showed that the expression of COLIII in the anterior vaginal wall (AVW) and COLIII, MMP-2 and -9 in the uterosacral ligament (USL) were consistent with the overall results. However, the expression of COLI and MMP-1 in the AVW showed no difference and the expression of COLI and MMP-1 in the USL is still controversial based on current studies. CONCLUSIONS: Patients with POP have lower expression of COLI and TIMP-1 and higher expression of COLIII and MMPs compared with non-POP cases, but further studies are required to investigate in specified anatomical sites.

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid.

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.

Clinical features of patients with previous spontaneous rupture of ovarian endometrioma operated electively: a case-control study.

BACKGROUND: The aim of the study is to investigate the proportion and clinical features of previous spontaneously ruptured ovarian endometrioma among women who underwent elective surgery for endometrioma. METHODS: This retrospective study was based on a cohort of elective surgeries for endometrioma performed by the same gynecologic team at Peking Union Medical College Hospital from January 2017 to October 2022. Patients diagnosed with previous spontaneously ruptured endometrioma during elective surgery were enrolled in the ruptured group. In the same cohort, patients with unruptured endometrioma treated during the same period were selected as the unruptured group by 1:2 matching according to age. Demographic and clinical information were collected and compared between two groups. RESULTS: A total of 422 patients in the cohort were diagnosed with endometrioma. There were 38 patients (9.0%) in ruptured group and 76 patients in unruptured group. All enrolled participants were treated by laparoscopic surgery. In ruptured group, 86.8% patients had a history of acute abdominal pain, which was only 13.2% in unruptured group (P < 0.001). Compared to unruptured group, patients diagnosed with ruptured endometrioma had a lower BMI (P = 0.021), larger maximum diameter of endometrioma (P = 0.040), higher proportion of cul-de-sac partial obliteration rather than complete obliteration (P = 0.003). CONCLUSIONS: Spontaneous rupture of endometrioma is not rare. The proportion of spontaneous rupture of endometrioma in our study was higher than that reported in the literatures. In women with endometrioma, the onset of acute abdominal pain should be considered a rupture of cyst, especially in patients with big cysts.

Ambient fine particulate matter and cardiopulmonary health risks in China.

ABSTRACT: In China, the level of ambient fine particulate matter (PM 2.5 ) pollution far exceeds the air quality standards recommended by the World Health Organization. Moreover, the health effects of PM 2.5 exposure have become a major public health issue. More than half of PM 2.5 -related excess deaths are caused by cardiopulmonary disease, which has become a major health risk associated with PM 2.5 pollution. In this review, we discussed the latest epidemiological advances relating to the health effects of PM 2.5 on cardiopulmonary diseases in China, including studies relating to the effects of PM 2.5 on mortality, morbidity, and risk factors for cardiovascular and respiratory diseases. These data provided important evidence to highlight the cardiopulmonary risk associated with PM 2.5 across the world. In the future, further studies need to be carried out to investigate the specific relationship between the constituents and sources of PM 2.5 and cardiopulmonary disease. These studies provided scientific evidence for precise reduction measurement of pollution sources and public health risks. It is also necessary to identify effective biomarkers and elucidate the biological mechanisms and pathways involved; this may help us to take steps to reduce PM 2.5 pollution and reduce the incidence of cardiopulmonary disease.

Identification of the Active Compound of Liu Wei Di Huang Wan for Treatment of Gestational Diabetes Mellitus via Network Pharmacology and Molecular Docking.

Liu Wei Di Huang Wan (LWDHW) is a well-known Chinese herbal compound, which has been prescribed for the treatment of gestational diabetes mellitus (GDM). We sought to clarify the potential therapeutic effects of LWDHW against GDM. Differentially expressed genes (DEGs) in GDM were firstly identified from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal the biological functions of the DEGs. Subsequently, the LWDHW-compound-target network was constructed based on public databases to identify the relationship between the active components in LWDHW and the corresponding targets. Furthermore, gene functional analysis and protein-protein interaction (PPI) network construction were applied to investigate the function of potential targets and to evaluate hub genes. Finally, molecular docking was used to verify the binding activities between active ingredients and hub targets. Thirteen active components and 39 corresponding therapeutic target genes were obtained via network pharmacology analysis. The enrichment analysis demonstrated that the anti-GDM effect of LWDHW included oxidoreductase activity, involvement in renal system process, and regulation of blood pressure, which may be achieved through regulation of serotonergic synapses, vascular smooth muscle contraction, and neuroactive ligand-receptor interaction pathways. Additionally, molecular docking revealed that the main active component, Mu Dan Pi, exhibited the best affinity for proteins encoded by hub genes. This study applied network pharmacology analysis and molecular docking to display the multicomponent and multitarget characteristics of LWDHW in the treatment of GDM. Our findings provide novel insights into the pathogenesis of GDM and the therapeutic mechanisms of LWDHW against GDM.

SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK.

Salt-inducible kinase 2 (SIK2; also known as serine/threonine-protein kinase SIK2) is overexpressed in several cancers and has been implicated in cancer progression. However, the mechanisms by which SIK2 regulates cancer cell motility, migration and metastasis in ovarian cancer have not been fully discovered. Here, we identify that SIK2 promotes ovarian cancer cell motility, migration and metastasis in vitro and in vivo. Mechanistically, SIK2 regulated cancer cell motility and migration by myosin light chain kinase, smooth muscle (MYLK)-meditated phosphorylation of myosin light chain 2 (MYL2). SIK2 directly phosphorylated MYLK at Ser343 and activated its downstream effector MYL2, promoting ovarian cancer cell motility and metastasis. In addition, we found that adipocytes induced SIK2 phosphorylation at Ser358 and MYLK phosphorylation at Ser343, enhancing ovarian cancer cell motility. Moreover, SIK2 protein expression was positively correlated with the expression of MYLK-pS343 in ovarian cancer cell lines and tissues. The co-expression of SIK2 and MYLK-pS343 was associated with reduced median overall survival in human ovarian cancer samples. Taken together, SIK2 positively regulates ovarian cancer motility, migration and metastasis, suggesting that SIK2 is a potential candidate for ovarian cancer treatment.

Identification of Candidate Gene Signatures and Regulatory Networks in Endometriosis and its Related Infertility by Integrated Analysis.

Endometriosis is a common gynecological disease associated with infertility, and it represents an economic burden worldwide. However, the molecular mechanisms underlying endometriosis development have not yet been fully elucidated. Here, we aimed to identify reliable key genes and the related regulatory network that may be involved in endometriosis. Differentially expressed genes (DEGs) were identified through integrated analysis of four expression datasets of endometriosis from Gene Expression Omnibus. Gene functional analysis and protein-protein interaction network construction were performed to reveal the potential function of DEGs. Subsequently, candidate hub genes were defined and validated in GSE105764 dataset, and the associated regulatory networks were constructed. Additionally, GSE120103 dataset was applied to identify the differential expression between the infertile and fertile groups of patients with stage IV endometriosis. Finally, real-time quantitative polymerase chain reaction analysis was performed to identify the differential expression of hub genes in the collected clinical specimens. Robust rank aggregation integrated analysis determined 158 DEGs. Epithelial cell differentiation was the most significantly enriched biological process, and leukocyte transendothelial migration was the most significantly enriched pathway. Eight hub genes including CLDN3, CLDN5, CLDN7, CLDN11, HOXC8, HOXC6, HOXB6, and HOXB7 were identified, and most of these were validated as abnormally expressed genes in both the infertile group and patients with endometriosis. Transcriptional factors and microRNAs related to these genes were identified. Altogether, our integrated analysis identified critical gene signatures, involved pathways, and regulatory networks, which could provide clinically significant insights into the molecular mechanisms underlying endometriosis and its related infertility.

MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway.

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional enzyme located in the mitochondria. MTHFD2 has been reported to be overexpressed in several malignant tumors and is implicated in cancer development. This study aimed to investigate the effect of MTHFD2 on ovarian cancer progression. The expression of MTHFD2 was detected by bioinformatic analysis, immunohistochemistry, RT-qPCR (real-time quantitative PCR analysis), and western blot analysis. The effects of MTHFD2 depletion on cell proliferation, migration, and invasion were determined through in vitro experiments. Cell cycle progression and apoptosis were accessed by flow cytometry. The related signaling pathway protein expression was determined by western blot analysis. We found that MTHFD2 is highly expressed in both ovarian cancer tissues and cell lines. MTHFD2 deletion suppressed cell proliferation and metastasis. Knockdown of MTHFD2 induces cell apoptosis and G2/M arrest, whereas the number of cells in S phase increased with MTHFD2 overexpression. Mechanically, our results indicate that an inhibitory effect of MTHFD2 knockdown may be mediated by the downregulation of cyclin B1/Cdc2 complex and the inhibitory effect on its activity. Additionally, MTHFD2 could regulate cell growth and aggressiveness via activation of STAT3 and the STAT3-induced epithelial-mesenchymal transition signaling pathway. These findings indicate that MTHFD2 is overexpressed in ovarian cancer and regulates cell proliferation and metastasis, presenting an attractive therapeutic target.

2D bimetallic Ni/Fe MOF nanosheet composites as a peroxidase-like nanozyme for colorimetric assay of multiple targets.

In this contribution, 2D Ni/Fe MOF nanosheets were synthesized by a simple two-step ultrasound strategy at room temperature, i.e. the 2D Ni-MOF with a lamellar structure was first synthesized by the top-down ultrasonic assisted stripping route, followed by introducing Fe3+ ions as a metal node and terephthalic acid as an organic ligand to form 2D Ni/Fe MOF nanosheets that exhibited weak oxidase-like and strong peroxidase-like properties. Relative to that of the single metal Ni-MOF and Fe-MOF, the peroxidase-mimicking capability of the 2D Ni/Fe MOF nanosheets increased by over 14-fold and 3-fold, respectively. Reactive oxygen trials indicated that the 2D Ni/Fe MOF nanosheets can efficiently catalyze the decomposition of H2O2 to generate the ˙OH and O2˙- radicals, which can oxidize TMB to oxTMB from colorless to blue. The kinetic trial demonstrated the high affinity of the 2D Ni/Fe MOF nanosheet to H2O2 with a Km of 0.037 mM, which was 100 times lower than that of HRP. These impressive characteristics are likely related to the good dispersion of the in situ formed Fe MOF in the 2D Ni-MOF nanosheet structure with coordinatively unsaturated metal sites. This allows the 2D Ni/Fe MOF nanosheets to expose more active metal sites and to enhance the intrinsic catalytic activity of each site due to the synergistic interaction between the two metals. Interestingly, glutathione can obviously restrict the peroxidase-like activity of the 2D Ni/Fe MOF nanosheet, while the inhibited TMB oxidation can be restored upon further introducing Hg2+ ions due to the high and specific affinity of Hg2+ to thiol groups in glutathione. Based on the above facts, the 2D Ni/Fe MOF nanozyme was used to construct a nanoplatform to determine multiple targets, i.e. H2O2, glutathione and Hg2+. The 2D Ni/Fe MOF nanozyme-based colorimetric assay exhibits a linear response to H2O2, glutathione and Hg2+ ions over the 0.01-100 µM, 0.02-100 µM, and 100 nM to 200 µM ranges, respectively. The limits of detection (3σ) for the determination of H2O2, glutathione and Hg2+ are 10 nM, 10 nM, and 100 nM, respectively. This method was used to determinate the content of Hg2+ ions in real water samples.

[Component Characteristics and Source Appointment of Volatile Organic Compounds in Lianyungang City].

Volatile organic compounds (VOCs) are important precursors of ozone and particulate matter; thus, their impacts on air quality are particularly significant. To study the composition characteristics and sources of VOCs in Lianyungang City, four national control sites were selected to conduct VOCs sampling and analysis on typical days in spring, summer, and autumn. Concentrations of VOCs, the effects of different components of VOCs on ozone formation were quantified, and the sources of VOCs were analyzed using the Positive Matrix Factorization model. The VOC concentrations were in the range of 27.46×10-9-40.52×10-9 in spring, 45.79×10-9-53.45×10-9 in summer, and 38.84×10-9-46.66×10-9 in autumn. Concentrations of oxygenated compounds accounted for 41%-48% of all measured VOCs. VOC species with higher concentrations were acetone, acrolein, and propionaldehyde, and the concentration of isoprene was higher in summer. Generally, VOC concentrations were higher at 09:00 than at 13:00 when acrolein, ethylene, and dichloromethane concentrations changed greatly. The ozone formation potential (OFP) of oxygenated compounds was the highest, followed by aromatics and alkenes, and the OFP of alkanes was the smallest. The VOC species with higher OFP were acrolein, propylene, and ethylene. The main sources of VOCs in Lianyungang were industry (49%), solvent usage (23%), transportation (14%), paint usage (10%), and natural sources (4%). The results suggest further investigating the oxygenated compounds with higher concentrations and higher OFP in Lianyungang City, and studying the impacts of industrial sources on VOCs.

MiR-155 promotes interleukin-1ß-induced chondrocyte apoptosis and catabolic activity by targeting PIK3R1-mediated PI3K/Akt pathway.

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation, in which elevated chondrocyte apoptosis and catabolic activity play an important role. MicroRNA-155 (miR-155) has recently been shown to regulate apoptosis and catabolic activity in some pathological circumstances, yet, whether and how miR-155 is associated with OA pathology remain unexplored. We report here that miR-155 level is significantly up-regulated in human OA cartilage biopsies and also in primary chondrocytes stimulated by interleukin-1ß (IL-1ß), a pivotal pro-catabolic factor promoting cartilage degradation. Moreover, miR-155 inhibition attenuates and its overexpression promotes IL-1ß-induced apoptosis and catabolic activity in chondrocytes in vitro. We also demonstrate that the PIK3R1 (p85α regulatory subunit of phosphoinositide 3-kinase (PI3K)) is a target of miR-155 in chondrocytes, and more importantly, PIK3R1 restoration abrogates miR-155 effects on chondrocyte apoptosis and catabolic activity. Mechanistically, PIK3R1 positively regulates the transduction of PI3K/Akt pathway, and a specific Akt inhibitor reverses miR-155 effects on promoting chondrocyte apoptosis and catabolic activity, phenocopying the results obtained via PIK3R1 knockdown, hence establishing that miR-155 promotes chondrocyte apoptosis and catabolic activity through targeting PIK3R1-mediated PI3K/Akt pathway activation. Altogether, our study discovers novel roles and mechanisms of miR-155 in regulating chondrocyte apoptosis and catabolic activity, providing an implication for therapeutically intervening cartilage degradation and OA progression.

Investigation on direct electrochemical and electrocatalytic behavior of hemoglobin on palladium-graphene modified electrode.

Palladium-graphene (Pd-GR) nanocomposite was acted as modifier for construction of the modified electrode with direct electrochemistry of hemoglobin (Hb) realized. By using Nafion as the immobilization film, Hb was fixed tightly on Pd-GR nanocomposite modified carbon ionic liquid electrode. Electrochemical behaviors of Hb modified electrode were checked by cyclic voltammetry and a pair of redox peaks originated from direct electron transfer of Hb was appeared. The Hb modified electrode had excellent electrocatalytic activity to the reduction of trichloroacetic acid and sodium nitrite in the concentration range from 0.6 to 13.0mmol·L-1 and from 0.04 to 0.5 mmol·L-1. Therefore Pd-GR nanocomposite was proven to be a good candidate for the fabrication of third-generation electrochemical biosensor.