Limited underthrusting of India below Tibet: 3He/4He analysis of thermal springs locates the mantle suture in continental collision.

During continent­continent collision, does the downgoing continental plate underplate far inboard of the collisional boundary or does it subduct steeply into the mantle, and how is this geometry manifested in the mantle flow field? We test conflicting models for these questions for Earth's archetypal continental collision forming the Himalaya and Tibetan Plateau. Air-corrected helium isotope data (3He/4He) from 225 geothermal springs (196 from our group, 29 from the literature) delineate a boundary separating a Himalayan domain of only crustal helium from a Tibetan domain with significant mantle helium. This 1,000-km-long boundary is located close to the Yarlung-Zangbo Suture (YZS) in southern Tibet from 80 to 92°E and is interpreted to overlie the "mantle suture" where cold underplated Indian lithosphere is juxtaposed at >80 km depth against a sub-Tibetan incipiently molten asthenospheric mantle wedge. In southeastern Tibet, the mantle suture lies 100 km south of the YZS, implying delamination of the mantle lithosphere from the Indian crust. This helium-isotopic boundary helps resolve multiple, mutually conflicting seismological interpretations. Our synthesis of the combined data locates the northern limit of Indian underplating beneath Tibet, where the Indian plate bends to steeper dips or breaks off beneath a (likely thin) asthenospheric wedge below Tibetan crust, thereby defining limited underthrusting for the Tibetan continental collision.

Aerobic exercise promotes emotion regulation: a narrative review.

Aerobic exercise improves the three stages of emotion regulation: perception, valuation and action. It reduces the perception of negative emotions, encourages individuals to reinterpret emotional situations in a positive or non-emotional manner, and enhances control over emotion expression behaviours. These effects are generated via increased prefrontal cortex activation, the strengthening of functional connections between the amygdala and several other brain regions, and the enhancement of the plasticity of key emotion regulation pathways and nodes, such as the uncinate fasciculus. The effect of aerobic exercise on emotion regulation is influenced by the exercise intensity and duration, and by individuals' exercise experience. Future research may explore the key neural basis of aerobic exercise's promotion of emotion regulation.

Comparison of proprioception recovery following anterior cruciate ligament reconstruction using an artificial graft versus an autograft.

BACKGROUND: To compare proprioception recovery after anterior cruciate ligament reconstruction (ACLR) with a hamstring tendon autograft versus the artificial Ligament Advanced Reinforcement System (LARS). MATERIAL AND METHODS: Forty patients (9 females, 31 males) with anterior cruciate ligament (ACL) rupture were enrolled in this prospective study. Patients were randomized to two groups, 1) ACLR using a hamstring tendon autograft (n = 20) or 2) ACLR using artificial LARS (n = 20). Proprioception was assessed with knee joint position sense (JPS) passive-passive test at 45° and 75° flexions, with the contralateral healthy knee as a control baseline to calculate the JPS error. Knee JPS absolute error was used as the main outcome variable and defined as the absolute difference between the reproduction and target angles. RESULTS: JPS error in both groups at 3 months after ACLR was significantly higher than that at 12 months. However, no significant difference in JPS error was detected between the LARS and autograft groups at either 3 or 12 months after ACLR. Analyzing JPS data by grouping patients according to whether ACLR was performed more or less than 1 year following injury regardless of graft type showed a statistically significant difference between the groups at 3 months, but not at 12 months, after ACLR. Patients receiving the graft within 1 year of injury had a lower JPS error than those receiving the graft more than 1 year after injury at 3 months. No complications were associated with either ACLR method. CONCLUSION: ACLR with a hamstring tendon autograft or LARS artificial graft is similarly safe and effective for recovering knee proprioception.

3D-printed hemipelvic prosthesis combined with a dual mobility bearing in patients with primary malignant neoplasm involving the acetabulum: clinical outcomes and finite element analysis.

BACKGROUND: Limb salvage reconstruction for pelvic tumors, especially periacetabular tumors, is challenging. We combined the use of dual mobility bearing and 3D-printed hemipelvic prosthesis to improve function and reduce the probability of complications after hemi-pelvic resection in patients with primary acetabular malignancy. The purpose of this study was to evaluate the efficacy and safety of this combination. METHODS: Between October 2011 and May 2021, 11 patients with malignancies involving the acetabulum received hemipelvic replacement with a 3D-printed prosthesis and dual mobility bearing. Follow-up of postoperative survival, complications, and Musculoskeletal Tumor Society 93 (MSTS-93) lower limb functional scores were carried out. A finite element model of the postoperative pelvis was developed and input into the finite element analysis software. The Von Mises equivalent stress formula was used to analyze the stress distribution of each part of the pelvis under one gait cycle and the stress distribution at different angles of the hip joint. RESULTS: By the last follow-up, 9 of the 11 patients (81.8%) were still alive, and 2 patients had local tumor recurrence. The complications including 1 deep infection and 1 dislocation of the artificial joint. Excluding 1 amputation patient, the average score of the remaining 8 patients at the last follow-up was 21.4/30 (71.3%) on the MSTS-93. In the reconstructed pelvis, stress distributions were concentrated on the junction between hemipelvic prosthesis and screw and iliac bone on the resected side, and between femoral prosthesis stem and femoral bulb, while the stress of polyethylene lining was small. Before impact, the polyethylene lining will rotate at a small angle, about 3°. The inner stress of polyethylene liner is greater than the outer stress in all conditions. The polyethylene liner has no tendency to slide out. CONCLUSION: Pelvic tumor resection and reconstruction using 3D-printed hemipelvic prosthesis combined with dual mobility bearing was an effective treatment for pelvic tumors. Our patients achieved good early postoperative efficacy and functional recovery. The dual mobility bearing is beneficial to prevent dislocation, and the mechanical distribution and wear of the prosthesis are acceptable.

Simultaneous determination of interfacial molarities of an alcohol, bromide ion, and water during an alcohol induced microstructural transition: the difference between medium and long chain alcohols.

The transitions between surfactant aggregate structures are triggered by changes in chemical or physical stimulations, including addition of additives. Effects of added alcohols on aggregate morphologies correlate strongly with alcohol chain length. The local molarities of alcohol, water, and counterions in the interfacial regions play an important role in controlling the aggregate morphologies. However, direct experimental estimates of changes of interfacial alcohol molarities during alcohol induced micelle-to-vesicle transitions have never been reported. Ellipsoidal-wormlike micelle-vesicle transitions in CTAB/KBr aqueous solutions in the presence of long-chain octanol were characterized by using combined rheological, dynamic light scattering (DLS), transmission electron microscopy (TEM) and turbidity measurements. However, the transitions are absent with added butanol. The chemical trapping method (CT) was employed to understand the differences between medium- and long-chain alcohols in determining aggregate morphology. The CT method was used to estimate interfacial water, alcohol, and counterion molarities with increasing stoichiometric alcohol concentrations. With 55 mM alcohol added, the interfacial octanol molarity is 0.9 M, which is three times higher than that for butanol. With added octanol, the ellipsoidal-wormlike micelle-vesicle transition is accompanied by a concurrent sharp increase of interfacial water molarities and a decrease of interfacial counterion molarity, which is not observed with added butanol. The CT data was also employed to estimate the changes of Israelachvili's packing parameter with increasing added alcohol concentration. Our result provides critical molecular level information for understanding the morphological transitions of CTAB/additives.

Long Non-Coding RNA (LncRNA) CAIF is Downregulated in Osteoarthritis and Inhibits LPS-Induced Interleukin 6 (IL-6) Upregulation by Downregulation of MiR-1246.

BACKGROUND Osteoarthritis (OA) affects about 40% of people older than 40 years of age, and the mechanism is not well understood. Long non-coding RNA (lncRNA) CAIF is a recently identified critical player in myocardial infarction, while its role in other human diseases is unclear. The present study aimed to investigate the role of CAIF in OA. MATERIAL AND METHODS Levels of CAIF in synovial fluid of OA patients (n=60) and healthy controls (n=60) were measuring by performing quantitative real-time polymerase chain reaction (qRT-PCR). MiR-1246 and interleukin (IL)-6 levels in synovial fluid were measured by performing qRT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell apoptosis analysis was performed after CHON-001 cells were treated with 500 mg/mL lipopolysaccharide (LPS) for 24 hours. RESULTS We found that CAIF in synovial fluid was downregulated in OA patients and inversely correlated with miR-1246 and IL-6. Downregulated CAIF distinguished OA patients from healthy controls. In cells of chondrogenic cell line CHON-001, CAIF overexpression mediated the inhibited expression of miR-1246 and secretion of IL-6, while miR-1246 overexpression reduced the effects of CAIF overexpression on IL-6 secretion. In addition, CAIF overexpression inhibited the apoptosis of CHON-001 cells under LPS treatment, while miR-1246 overexpression attenuated the effects of CAIF overexpression. CONCLUSIONS Therefore, CAIF may downregulate miR-1246 to improve OA.

RBFOX3 Regulates the Chemosensitivity of Cancer Cells to 5-Fluorouracil via the PI3K/AKT, EMT and Cytochrome-C/Caspase Pathways.

BACKGROUND/AIMS: RBFOX3, an RNA-binding fox protein, plays an important role in the differentiation of neuronal development, but its role in the chemosensitivity of hepatocellular carcinoma (HCC) to 5-FU is unknown. METHODS: In this study, we examined the biological functions of RBFOX3 and its effect on the chemosensitivity of HCC cells to 5-FU in vitro and in a mouse xenograft model. RESULTS: RBFOX3 was found to have elevated expression in HCC cell lines and tissue samples, and its knockdown inhibited HCC cell proliferation. Moreover, knockdown of RBFOX3 improved the inhibitory effect of 5-fluorouracil (5-FU) on cell proliferation, migration and invasion, and enhanced the apoptosis induced by 5-FU. However, overexpression of RBFOX3 reduced the inhibitory effect of 5-fluorouracil (5-FU) on cell proliferation, migration and invasion, and decreased the apoptosis induced by 5-FU. We further elucidated that RBFOX3 knockdown synergized with 5-FU to inhibit the growth and invasion of HCC cells through PI3K/AKT and epithelial-mesenchymal transition (EMT) signaling, and promote apoptosis by activating the cytochrome-c/caspase signaling pathway. Finally, we validated that RBFOX3 regulated 5-FU-mediated cytotoxicity in HCC in mouse xenograft models. CONCLUSIONS: The findings from this study indicate that RBFOX3 regulates the chemosensitivity of HCC to 5-FU in vitro and in vivo. Therefore, targeting RBFOX3 may improve the inhibition of HCC growth and progression by 5-FU, and provide a novel potential therapeutic strategy for HCC.

Translation and validation of the simplified Chinese version of the anterior cruciate ligament-return to sport after injury (ACL-RSI).

PURPOSE: The aim of this study is to obtain a translation and adaptation of the anterior cruciate ligament-return to sport after injury (ACL-RSI) into simplified Chinese and validate the simplified Chinese version. METHODS: Translation and adaptation were performed according to the guidelines of the American Academy of Orthopaedic Surgeons Outcome Committee. A total of 122 patients who were diagnosed with an ACL injury and underwent primary arthroscopic anterior cruciate ligament reconstruction (ACLR) between 2015 and 2016 were included in this study. The simplified Chinese version of the ACL-RSI (SC-ACL-RSI), Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm score and International Knee Documentation Committee (IKDC) subjective knee form were completed. Psychometric evaluations included score distribution, internal consistency, test-retest reliability, and construct and discriminant validity. RESULTS: SC-ACL-RSI scores exhibited a normal distribution without ceiling and floor effects. Internal consistency was high (Cronbach's alpha = 0.94). The intraclass correlation coefficient was 0.98, indicating excellent test-retest reliability. SC-ACL-RSI scores were correlated with all KOOS subscales (r = 0.30 to 0.69, p < 0.001), the IKDC subjective knee form (r = 0.46, p < 0.001) and the Lysholm score (r = 0.56, p < 0.001). The mean scores between patients who returned to the same preinjury level of sport (65.1 ± 14.3) and those who could not return to the same level (51.0 ± 15.0) were significantly different (p < 0.001). CONCLUSIONS: The SC-ACL-RSI is a reliable and valid instrument to evaluate the psychological impact of a patient returning to sport after ACLR. It is important to evaluate patients' ability to return to sport after an ACL injury. The information provided by the SC-ACL-RSI will affect decisions regarding treatment and rehabilitation plans, which are more likely to influence clinical outcomes. LEVEL OF EVIDENCE: II.

Comparison of artificial graft versus autograft in anterior cruciate ligament reconstruction: a meta-analysis.

BACKGROUND: Critically evaluation and summarization for the outcomes between autografts and artificial grafts using in anterior cruciate ligament (ACL) reconstruction have not been performed currently. The purpose of this study is to compare the clinical outcomes between artificial ligaments and autografts at a short- to mid-term follow-up. METHODS: A computerized search of the databases was conducted including Medline, Embase, and the Cochrane library. Only prospective or retrospective comparative studies with a minimum 2-year follow-up and a minimum sample size of 15 for each group were considered for inclusion. Two independent reviewers performed data extraction and methodological quality assessment. A Mantel-Haenszel analysis was used for pooling of results. Sensitivity analysis was performed in order to maintain the stability of results. RESULTS: Seven studies were included in this study. The total sample size was 403 (autograft group: 206 patients; synthetic graft group: 197 patients). Four studies were randomized controlled trials. Two studies were retrospective comparative studies and one study was non-randomized prospective comparative study. In terms of instrumented laxity, patient-oriented outcomes and complications, no significant difference was occurred between new artificial ligaments and autografts. But the results of IKDC grades and instrumented laxity were worsen in early artificial ligaments compared to autografts. CONCLUSIONS: The outcomes of new generation of artificial ligaments are similar to autografts at a short- to mid-term follow-up. However, the early artificial ligaments are not suggested for ACL reconstruction compared to autografts.

Expression and clinical evidence of miR-494 and PTEN in non-small cell lung cancer.

The aim of this study was to explore the expression and clinical significance of miR-494 and PTEN (phosphatase and tensin homologue deleted on chromosome ten) in non-small cell lung cancer (NSCLC). Immunohistochemistry for PTEN and in situ hybridization (ISH) for miR-494 were performed in 92 NSCLC tissues and 10 normal lung tissues to detect their expression, and correlation between their expression with clinical characteristics and prognosis was analyzed. The expression of miR-494 was significantly higher in NSCLC than in normal lung tissues (P = 0.004). The positive expression of PTEN protein in the lung carcinoma tissues was significantly lower than that in the normal lung tissues (P = 0.013), while the level of miR-494 expression was negatively correlated with PTEN expression (r = -0.577, P < 0.01). The high positive rate of miR-494 was positively correlated with pathological TNM (p-TNM) staging and lymph node metastasis. The expression of miR-494 was negatively correlated with grade of differentiation. However, the expression of PTEN was positively correlated with grade of differentiation. Patients with over-expression of miR-494 had a shorter overall survival (OS), while the negative group of PTEN was correlated with poor OS. MiR-494 over-expression and low PTEN expression are closely related to tumor p-TNM staging and lymph node metastasis, differentiation, and OS. Combined detection of PTEN and miR-494 can aid in determining malignancy degree and the prognosis of patients with NSCLC. MiR-494 may be served as a novel prognostic factor and may lead to new treatment strategies for NSCLC.

Effects of chronic aerobic exercise on attentional bias among women with methamphetamine addiction.

Objective: To explore the effects of chronic exercise on attentional bias toward drug-related stimuli and on brain electrophysiological characteristics among women with methamphetamine addiction. Methods: In total, 63 women with methamphetamine addiction were randomized to participate in a dance (n = 21; mean age, 32.16 ± 2.07 years), bicycle (n = 21; mean age, 32.59 ± 2.12 years), or control (maintained regular activities with little exercise; n = 21; mean age, 30.95 ± 2.81 years) group for 12 weeks. The participants in the three groups were not significantly different in terms of methamphetamine use or detoxification. Before and after the intervention, attentional bias was assessed using the dot-probe task, and event-related potentials were recorded during the task. Results: The mean attentional bias scores decreased significantly after the intervention in both exercise groups but not in the control group. After 12 weeks of dance exercise, the amplitudes of the N170, N2, P2, and P3 components of the event-related potentials decreased significantly during attentional bias processing. In addition, differences in N170 amplitudes for congruent vs. incongruent conditions in the dot-probe task were no longer observed. After 12 weeks of cycling exercise, N2 and P2 amplitudes decreased significantly. By contrast, there were no significant differences in N170, N2, P2, and P3 amplitudes in the control group before vs. after the intervention. Conclusions: Chronic (12 weeks of) aerobic exercise reduced attentional bias toward drug-related cues by improving attentional inhibition and reducing the maintenance of extra attention to drug-related cues among women with methamphetamine addiction. Both dance and bicycle exercise improved the early recognition of drug-related cues, weakened the influence of the memory of previous drug use, and improved attentional bias behavior by strengthening attention control. Dance exercise, but not bicycling, also regulated emotional control and improved the attention selection process. These results provide theoretical and empirical evidence that chronic aerobic exercise may reduce the attentional bias toward drug-related cues to assist in the recovery of women with methamphetamine addiction.

Motor experience modulates neural processing of lexical action language: Evidence from rugby players.

The perceptual symbol theory proposes a sensorimotor simulation in language processing, emphasizing the role of motor experience. However, the neural basis of motor experience on lexical-level language processing remains little known. In the current fMRI study, we compared brain activation and task-based functional connectivity in 28 rugby players and 28 novices during rugby- specialized and daily verb processing. Distinct differences were observed between the two groups in the bilateral superior temporal gyrus and left angular gyrus regions during specialized verb processing. Notably, intergroup functional connectivity was evident between the left superior temporal gyrus and the right precentral gyrus during specialized verb processing. This study contributes insights into the neural responses and connectivity patterns associated with motor experience at the lexical level, highlighting its potential impact on language processing.

Air Gap Fiber Bragg Grating for Simultaneous Strain and Temperature Measurement.

We propose an air gap fiber Bragg grating (g-FBG) sensor that can measure strain and temperature simultaneously. The sensor is made by aligning two fiber Bragg gratings (FBGs), and an air gap exists between these two sub-gratings. This sensor's architecture allows it to form a spectrum with phase-shifted fiber Bragg grating (PSFBG) spectroscopy and Fabry-Perot interference (FPI) spectroscopy. Since the sensitivity of PSFBG and FPI spectra is different for strain and temperature, it is possible to measure both strain and temperature by measuring one of the reflected dips of PSFBG and the interference dip of FPI. The experimental results show that the strain sensitivity is about 11.95 pm/µÎµ via the dip wavelength detection of FPI, and the temperature sensitivity is about 9.64 pm/°C via the dip wavelength detection of PSFBG. The g-FBG sensor demonstrates a resolution of approximately ±3.7 µÎµ within the strain range of 0 to 1000 µÎµ and about ±0.6 °C within the temperature range of 25 °C to 120 °C. The proposed g-FBG sensor, characterized by its simple structure, compact size, and cost-effectiveness, exhibits significant potential in the field of multi-parameter measurements.

Serum oxidative stress factors predict myocardial ischemia reperfusion injury after percutaneous coronary intervention in patients with acute myocardial infarction and type 2 diabetes mellitus.

Introduction: Serum oxidative stress factors may be considered to be essential parameters for indicating cell oxidative damage. Aim: We designed this study to investigate the clinical diagnostic value of serum oxidative stress factors (superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO)) combined with ischemia-modified albumin (IMA) and heat shock protein 70 (HSP70) for myocardial ischemia-reperfusion injury (MIRI) after percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM). Material and methods: From November 2020 to August 2021, 94 patients with AMI + T2DM and 86 patients with AMI were enrolled in the study; they were sub-grouped into the MIRI and non-MIRI groups following the occurrence of MIRI within 48 h after PCI. SOD, MDA, MPO, IMA, and HSP70 levels were determined. The clinical values of the combined serum oxidative stress factors, IMA, and HSP70 levels to predict MIRI events were analyzed. Results: There was a higher probability of MIRI events in the AMI + T2DM group than the AMI group (p < 0.05). The ROC curve for the combined prediction of SOD, MDA, MPO, IMA, and HSP70 for the occurrence of MIRI events was higher in both the AMI and the AMI + T2DM groups than for predictive factors alone (all p < 0.05). Conclusions: Combined prediction of SOD, MDA, MPO, IMA, and HSP70 has the highest diagnostic value for predicting MIRI events after PCI in AMI patients, especially in patients with AMI combined with T2DM.

Influencing pathways and toxicity changes of pre-ozonation on carcinogenic NDEA formation from greenhouse gas adsorbent DEAPA in subsequent disinfection processes.

This study was to evaluate the feasibility of controlling carcinogenic nitrosodiethylamine (NDEA) formation from greenhouse gas adsorbent 3-diethylaminopropylamine (DEAPA) by pre-O3 in subsequent chlorination/chloramination processes. The result indicated that the NDEA yields (0.4 %) during chlorination was 1.3 times of that during chloramination (0.3 %); pre-oxidation with 4 mg/L O3 significantly cut down its formation; the reduction rates were up to 67.5 and 48.5 %, respectively. OH scavenger greatly augmented the final NDEA amount from 1.86 to 5.05 µg/L during ozonation, while its roles on subsequent processes differed with disinfection methods as well as O3(g) dosages. Most of co-existed substances inhibited NDEA generation, except NO2-, CO32- and SO42-, which slightly promoted during ozonation. Basing on Gaussian calculation, GC/MS and UPLC-Q-TOF-MS analysis, the influencing mechanisms of pre-O3 on NDEA formation in subsequent disinfection processes were proposed. In addition, the calculated toxicity analysis as well as the whole toxicity was applied to evaluate the possibility of pre-O3 on risk control.

Fluorescence Properties of ZnOQDs-GO-g-C3N4 Nanocomposites.

In this paper, the fluorescence properties of ZnOQD-GO-g-C3N4 composite materials (ZCGQDs) were studied. Firstly, the addition of a silane coupling agent (APTES) in the synthesis process was explored, and it was found that the addition of 0.04 g·mL-1 APTES had the largest relative fluorescence intensity and the highest quenching efficiency. The selectivity of ZCGQDs for metal ions was also investigated, and it was found that ZCGQDs showed good selectivity for Cu2+. ZCGQDs were optimally mixed with Cu2+ for 15 min. ZCGQDs also had good anti-interference capability toward Cu2+. There was a linear relationship between the concentration of Cu2+ and the fluorescence intensity of ZCGQDs in the range of 1~100 µM. The regression equation was found to be F0/F = 0.9687 + 0.12343C. The detection limit of Cu2+ was about 1.74 µM. The quenching mechanism was also analyzed.

Fibulin-2 Facilitates Malignant Progression of Hepatocellular Carcinoma.

BACKGROUND: Identification of biomarkers to assist in the clinical management of hepatocellular carcinoma represents an urgent requirement. Fibulin-2 is known to contribute to the development and progression of various cancer types. This research investigated the role of fibulin-2 in hepatocellular carcinoma and explored the possible mechanisms. METHODS: The expression of fibulin-2 in hepatocellular carcinoma was measured by bioinformatic analysis and confirmed by western blot and immunohistochemical staining in cell lines or patients' samples. The clinicopathologic features of hepatocellular carcinoma patients was analyzed. Cell viability assays were used to explore the role of fibulin-2 on proliferation in hepatocellular carcinoma. Western blot was conducted to uncover changes of protein expression of Ras-MEK-ERK1/2 pathway when Fibulin-2 was overexpressed or silenced. Flow cytometry analyses were used to determine the roles of fibulin-2 in the function of apoptosis and cell cycle. Subcutaneous xenograft mouse models showed the tumor growth pattern after fibulin-2 silence in vivo. RESULTS: We reported the upregulation of fibulin-2 in most hepatocellular carcinoma tissues and cells lines. Fibulin-2 promoted the proliferation of hepatocellular carcinoma cells in vitro by regulating Ras-MEK-ERK1/2 signaling pathway, whereas knockdown of fibulin-2 incurred the opposite effect on proliferation. Consistently, knockdown of fibulin-2 resulted in increased apoptosis and induced growth arrest during the G0/G1 phase transition. In vivo xenograft assessment confirmed that knockdown of fibulin-2 inhibited hepatocellular carcinoma tumor growth. CONCLUSIONS: Fibulin-2 exhibited tumor promotor activities in malignant progression of hepatocellular carcinoma. The results of the study highlighted the potential of fibulin-2 to be utilized as a promising biomarker and therapeutic target for hepatocellular carcinoma.

Transcriptional investigation of the toxic mechanisms of perfluorooctane sulfonate in rats based on an RNA-Seq approach.

Perfluorooctane sulfonate (PFOS) was widely used in industrial applications before it was listed as a persistent organic pollutant by the Conference of the Parties in the Stockholm Convention in 2009. Although the potential toxicity of PFOS has been studied, its toxic mechanisms remain largely undefined. Here, we investigated novel hub genes and pathways affected by PFOS to gain new conceptions of the toxic mechanisms of PFOS. Reduced body weight gain and abnormal ultra-structures in the liver and kidney tissues were spotted in PFOS-exposed rats, indicating successful establishment of the PFOS-exposed rat model. The transcriptomic alterations of blood samples upon PFOS exposure were analysed using RNA-Seq. GO analysis indicates that the differentially expressed gene-enriched GO terms are related to metabolism, cellular processes, and biological regulation. Kyoto encyclopaedia of gene and genomes (KEGG) and gene set enrichment analysis (GSEA) were conducted to identify six key pathways: spliceosome, B cell receptor signalling pathway, acute myeloid leukaemia, protein processing in the endoplasmic reticulum, NF-kappa B signalling pathway, and Fc gamma R-mediated phagocytosis. The top 10 hub genes were screened from a protein-protein interaction network and verified via quantitative real-time polymerase chain reaction. The overall pathway network and hub genes may provide new insights into the toxic mechanisms of PFOS exposure states.

Bone Marrow Mesenchymal Stem Cell Exosome Attenuates Inflammasome-Related Pyroptosis via Delivering circ_003564 to Improve the Recovery of Spinal Cord Injury.

Bone marrow mesenchymal stem cell (BMSC) is previously reported to present a certain effect on treating spinal cord injury (SCI), while the underlying mechanism is largely uncovered. Therefore, the current study aimed to investigate the involvement of exosome-delivered circRNA profile in the BMSC's effect on pyroptosis for SCI treatment. H2O2 treated rat primary neurons were cultured with normal medium, BMSC, BMSC plus GW4869, and BMSC-derived exosome, respectively, then inflammasome-related pyroptosis markers, and circRNA profiles were detected. Subsequently, circ_003564-knockdown BMSC exosome was transfected into H2O2 treated rat primary neurons and NGF-stimulated PC-12 cells. Furthermore, in vivo validation was conducted. BMSC and BMSC-derived exosome both decreased inflammasome-related pyroptosis markers including cleaved caspase-1, GSDMD, NLRP3, IL-1ß, and IL-18 in H2O2-treated neurons, while exosome-free BMSC (BMSC plus GW4869) did not obviously reduce these factors. Microarray assay revealed that BMSC (vs. exosome-free BMSC) and BMSC-derived exosome (vs. normal medium) greatly regulated circRNA profiles, which were enriched in neuroinflammation pathways (such as neurotrophin, apoptosis, and TNF). Among three functional candidate circRNAs (circ_015525, circ_008876, and circ_003564), circ_003564 was most effective to regulate inflammasome-related pyroptosis. Interestingly, circ_003564-knockdown BMSC exosome showed higher expression of inflammasome-related pyroptosis markers compared to negative-control-knockdown BMSC exosome in H2O2 treated primary neurons/NGF-stimulated PC-12 cells. In vivo, BMSC exosome improved the function recovery and decreased tissue injury and inflammasome-related pyroptosis in SCI rats, whose effect was attenuated by circ_003564 knockdown transfection. BMSC exosome attenuates inflammasome-related pyroptosis via delivering circ_003564, contributing to its treatment efficacy for SCI.

The NRF2-dependent transcriptional axis, XRCC5/hTERT drives tumor progression and 5-Fu insensitivity in hepatocellular carcinoma.

Human telomerase reverse transcriptase (hTERT) is highly expressed in many tumors and is essential for tumorigenesis and metastasis in multiple cancers. However, the molecular mechanisms underlying its high expression level in hepatocellular carcinoma (HCC) remain unclear. In this study, we identified X-ray repair cross-complementing 5 (XRCC5), a novel hTERT promoter-binding protein in HCC cells, using biotin-streptavidin-agarose pull-down assay. We found that XRCC5 was highly expressed in HCC cells, in which it transcriptionally upregulated hTERT. Functionally, the transgenic expression of XRCC5 promoted HCC progression and 5-fluorouracil resistance, whereas short hairpin RNA knockdown of XRCC5 had converse effects in vitro and in vivo. Moreover, hTERT overexpression reversed XRCC5 knockdown- or 5-fluorouracil (5-Fu)-mediated HCC inhibition. Mechanistically, nuclear-factor-erythroid-2-related factor 2 (NRF2) interacted with XRCC5, which in turn upregulated hTERT. However, the upregulation was insignificant when NRF2 was reduced, suggesting that the XRCC5-mediated hTERT expression was NRF2 dependent. The HCC patients with high expression levels of XRCC5 and hTERT had shorter overall survival times compared with those with low XRCC5 and hTERT levels in their tumor tissues. Collectively, our study demonstrates the molecular mechanisms of the XRCC5/NRF2/hTERT signaling in HCC metastasis, which will aid in the identification of novel strategies for the diagnosis and treatment of HCC.