Significance Our regional-scale geochemical dataset ( 3 He/ 4 He) resolves the geometry of the continental collision between India and Asia. Geophysical images have led to contradictory interpretations that India directly underthrusts Tibet as a horizontal plate or India subducts steeply into the mantle. Helium transits from mantle depths to the surface within a few millennia, such that the ratio of mantle-derived 3 He to dominantly crust-derived 4 He provides a snapshot of the subsurface. 3 He/ 4 He data from 225 geothermal springs across a >1,000-km-wide region of southern Tibet define a sharp boundary subparallel to the surface suture between India and Asia, just north of the Himalaya, delineating the northern limit of India at ∼80-km depth. The India–Asia collision resembles oceanic subduction with an asthenospheric mantle wedge.

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.

Krüppel-like factor 4 (KLF4) is a transcription factor that contributes to diverse cellular processes and serves as a tumor suppressor or oncogene in various cancers. Previously, we have reported on the tumor suppressive function of KLF4 in lung cancer; however, its precise regulatory mechanism remains elusive. In this study, we found that KLF4 negatively regulated hTERT expression and telomerase activity in lung cancer cell lines and a mouse model. In addition, the KLF4 and hTERT expression levels were significantly related to the clinicopathological features of lung cancer patients. Promoter reporter analyses revealed the decreased hTERT promoter activity in cells infected with Ad-KLF4, and chromatin immunoprecipitation analysis demonstrated that endogenous KLF4 directly bound to the promoter region of hTERT. Furthermore, the MAPK signaling pathway was revealed to be involved in the KLF4/hTERT modulation pathway. Forced expression of KLF4 profoundly attenuated lung cell proliferation and cancer formation in a murine model. Moreover, hTERT overexpression can partially rescue the KLF4-mediated suppressive effect in lung cancer cells. Taken together, these results demonstrate that KLF4 suppresses lung cancer growth by inhibiting hTERT and MAPK signaling. Additionally, the KLF4/hTERT/MAPK pathway is a potential new therapeutic target for human lung cancer.

Melanoma is one of the most aggressive and lethal cancers. Discovery and identification of novel therapeutic targets is urgently needed. In this study, we demonstrated that ribosomal protein S3 (RPS3) was a potential target involved in melanoma growth. Knockdown of RPS3 by siRNA suppressed cell growth and induced apoptosis in melanoma cells. Further mechanism studies showed that RPS3 knockdown in melanoma cells triggered the release of cytochrome C (Cyto C) from mitochondrial, increased the location of BID on mitochondrial membrane and the cleavage of the pro-apoptotic proteins (PARP, caspase-3 and -9), promoted the opening of mitochondrial permeability transition pore and the flooding of calcium ions (Ca2+) into the mitochondrial, and decreased the expression of the Ca2+ gatekeeper MICU1 and its location on the mitochondrial. We also found that knockdown of RPS3 significantly inhibited tumor growth in a melanoma xenograft mouse model. Furthermore, we showed that RPS3 was highly expressed in melanoma cell lines and melanoma tumor tissues, and overexpression of RPS3 was associated with the poor prognosis of melanoma patients. Our results therefore demonstrate that RPS3 regulates melanoma growth through the modulation of the Cyto C/Ca2+/MICU1 dependent mitochondrial signaling and suggest that RPS3 is a potential therapeutic target for melanoma treatment.

The structure of the lithosphere-asthenosphere system is fundamental to understanding plate tectonics and Earth's evolution. Continental lithosphere, which is far more complicated than its oceanic counterpart due to the imprints left by numerous geologic processes during its long life, has drawn great attention from the seismological community (e.g.,

The aim of our study was to assess the medium-term clinical outcomes of anterior cruciate ligament (ACL) reconstruction using the Ligament Advanced Reinforcement System (LARS) artificial ligament.A total of 168 patients who underwent arthroscopic ACL reconstruction with the LARS artificial ligament in our department were enrolled in our research. Only 125 met the inclusion/exclusion criteria, and 91 could ultimately be contacted to participate in our research. The mean follow-up was 92 ± 19 months. Physical examinations and a KT-1000 arthrometer were used to evaluate knee laxity. The International Knee Documentation Committee (IKDC) and Lysholm knee scales were evaluated for knee function. The Tegner score was tested for the condition of return to sport. Range of motion (ROM) and the rates of failure and complications were calculated.Among all patients enrolled in the study, the failure rate was 4.4%, and the overall complication rate was 2.2%. Knee laxity measured by the KT-1000 arthrometer was 1.4 ± 1.5 mm, compared with the preoperative value of 5.1 ± 1.3 mm. The Lysholm score improved from a preoperative value of 54.6 ± 14.3 to a postoperative value of 85.4 ± 12.1. The proportion of return to sport was 86.8% (79/91). The postoperative Tegner score was 4.7 ± 1.3, while its value before injury was 5.5 ± 1.0.In this study, ACL reconstruction using the LARS artificial ligament has a good prognosis with a low failure and complication rate at a mean follow-up of 91 months.Abbreviations: ACL = anterior cruciate ligament, BPTB = one-patellar tendon-bone, FDA = Food and Drug Administration, IKDC = the International Knee Documentation Committee, LARS = the Ligament Advanced Reinforcement System, PET = polyethylene terephthalate, ROM = range of motion.

Activation of the telomere maintenance mechanism is a key hallmark of cancer. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, which is highly expressed in more than 80% of tumors, including hepatocellular carcinoma (HCC). However, the exact mechanisms by which hTERT is up-regulated in HCCs and promotes tumor growth and progression is not fully understood. The aim of this study was to discover the novel molecular targets that modulate hTERT signaling and HCC growth. In this study, we pulled down and identified RBFOX3 (RNA binding protein fox-1 homolog 3) as a novel hTERT promoter-binding protein in HCC cells using biotin-streptavidin-agarose pull-down and proteomics approach, and validated it as a regulatory factor for hTERT signaling and tumor growth in HCCs. Knockdown of RBFOX3 suppressed the promoter activity and expression of hTERT and consequently inhibited the growth and progression of HCC cells in vitro and in vivo. The suppression of HCC growth mediated by RBFOX3 knockdown could be rescued by hTERT overexpression. Conversely, exogenous overexpression of RBFOX3 activated the promoter activity and expression of hTERT and promoted the growth and progression of HCC cells. Moreover, we found that RBFOX3 interacted with AP-2β to regulate the expression of hTERT. Furthermore, we demonstrated that RBFOX3 expression was higher in the tumor tissues of HCC patients compared to the corresponding paracancer tissues, and was positively correlated with hTERT expression. Kaplan-Meier analysis showed that the HCC patients with high levels of RBFOX3 and hTERT had poor prognosis. Collectively, our data indicate that RBFOX3 promotes HCC growth and progression and predicts a poor prognosis by activating the hTERT signaling, and suggest that the RBFOX3/hTERT pathway may be a potential therapeutic target for HCC patients.

Receiver function techniques are widely used in imaging crustal and mantle structure beneath a seismic station. The weak P-to-S conversions at deep seismic structures are usually masked by strong shallow reverberations when unconsolidated sediments are present below the station, making it nearly impossible to utilize receiver function techniques. We develop a method to estimate sediment and crustal structures beneath a seismic station based on wavefield downward continuation and decomposition method. The method parametrizes velocity structure beneath the station with a stack of constant velocity layers overlying a homogeneous half-space, and approximates the teleseismic P wave and its coda by the structural response to an incoming plane P wave. Our method is based on the principle that the upgoing S wavefield is absent in the half-space, and searches for the optimum velocity and thickness of the layers that give the minimum S-wave energy flux from the half-space to the layers. An iterative grid-search algorithm from the top to the bottom layers is employed to implement the search. In this study, we only use models comprising either only one crust layer or two layers (sediment + crust) with a half-space mantle, although models with more layers are also implementable. The method is especially useful in resolving seismic structure beneath a station sitting on unconsolidated sediments. It not only can be used to determine the sediment thickness and velocity structure, but also provides an effective way to generate subsurface receiver functions, which are formed by deconvolving the upgoing P wavefield from the upgoing S waves at the top of hardrock crust, and thus are free from shallow reverberations. The technique is applied to various synthetic data generated with different types of velocity model and noise levels, and appears to have good capability in recovering the input models. We further applied this method to teleseismic data recorded at a station inside the Songliao Basin in northeast China. The estimated sediment thickness and velocity agrees well with the results of previous activesource studies. The subsurface receiver functions also show a superior power in exposing the Moho Ps conversions, resulting in a well-defined peak in the H-κ domain, which are absent in the regular receiver function data.