Coherent interfaces govern direct transformation from graphite to diamond.

Understanding the direct transformation from graphite to diamond has been a long-standing challenge with great scientific and practical importance. Previously proposed transformation mechanisms1-3, based on traditional experimental observations that lacked atomistic resolution, cannot account for the complex nanostructures occurring at graphite-diamond interfaces during the transformation4,5. Here we report the identification of coherent graphite-diamond interfaces, which consist of four basic structural motifs, in partially transformed graphite samples recovered from static compression, using high-angle annular dark-field scanning transmission electron microscopy. These observations provide insight into possible pathways of the transformation. Theoretical calculations confirm that transformation through these coherent interfaces is energetically favoured compared with those through other paths previously proposed1-3. The graphite-to-diamond transformation is governed by the formation of nanoscale coherent interfaces (diamond nucleation), which, under static compression, advance to consume the remaining graphite (diamond growth). These results may also shed light on transformation mechanisms of other carbon materials and boron nitride under different synthetic conditions.

Serum microRNA-125b-5p expression in patients with dilated cardiomyopathy combined with heart failure and its effect on myocardial fibrosis.

OBJECTIVE: This paper was performed to decipher the serum microRNA (miR)-125b-5p expression in patients with dilated cardiomyopathy (DCM) combined with heart failure (HF) and its effect on myocardial fibrosis. METHODS: Serum miR-125b-5p expression, LVEDD, LVESD, LVEF, LVFS, and NT-proBNP levels were evaluated in clinical samples. A rat DCM model was established by continuous intraperitoneal injection of adriamycin and treated with miR-125b-5p agomir and its negative control. Cardiac function, serum TNF-α, hs-CRP, and NT-proBNP levels, pathological changes in myocardial tissues, cardiomyocyte apoptosis, and the expression levels of miR-125b-5p and fibrosis-related factors were detected in rats. RESULTS: In comparison to the control group, the case group had higher levels of LVEDD, LVESD, and NT-pro-BNP, and lower levels of LVEF, LVFS, and miR-125b-5p expression levels. Overexpression of miR-125b-5p effectively led to the improvement of cardiomyocyte hypertrophy and collagen arrangement disorder in DCM rats, the reduction of blue-stained collagen fibers in the interstitial myocardium, the reduction of the levels of TNF-α, hs-CRP, and NT-proBNP and the expression levels of TGF-1ß, Collagen I, and α-SMA, and the reduction of the number of apoptosis in cardiomyocytes. CONCLUSION: Overexpression of miR-125b-5p is effective in ameliorating myocardial fibrosis.

Photosynthetic bacteria-based whole-cell inorganic-biohybrid system for multimodal enhanced tumor radiotherapy.

The whole-cell inorganic-biohybrid systems show special functions and wide potential in biomedical application owing to the exceptional interactions between microbes and inorganic materials. However, the hybrid systems are still in stage of proof of concept. Here, we report a whole-cell inorganic-biohybrid system composed of Spirulina platensis and gold nanoclusters (SP-Au), which can enhance the cancer radiotherapy through multiple pathways, including cascade photocatalysis. Such systems can first produce oxygen under light irradiation, then convert some of the oxygen to superoxide anion (•O2-), and further oxidize the glutathione (GSH) in tumor cells. With the combination of hypoxic regulation, •O2- production, GSH oxidation, and the radiotherapy sensitization of gold nanoclusters, the final radiation is effectively enhanced, which show the best antitumor efficacy than other groups in both 4T1 and A549 tumor models. Moreover, in vivo distribution experiments show that the SP-Au can accumulate in the tumor and be rapidly metabolized through biodegradation, further indicating its application potential as a new multiway enhanced radiotherapy sensitizer.

Cognitive impairment and depression precede increased HDL-C levels in middle-aged and older Chinese adults: cross-lagged panel analyses.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. METHODS: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. RESULTS: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (ß = - 0.036 and ß = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (ß = - 0.008 and ß = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (ß = - 0.026 and ß = - 0.053, respectively, P < 0.05). CONCLUSIONS: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.

Efficacy and safety of laminoplasty combined with C3 laminectomy for patients with multilevel degenerative cervical myelopathy: a systematic review and meta-analysis.

PURPOSE: Laminoplasty (LP) combined with C3 laminectomy (LN) can effectively achieve spinal cord decompression while maintaining the integrity of the posterior ligament-muscle complex, thereby minimizing cervical muscle damage. However, its necessity and safety remain controversial. This study aimed to compare the safety and efficacy of LP and LP combined with C3 LN in the treatment of patients with multilevel degenerative cervical spondylotic myelopathy (DCM). METHODS: A systematic review and meta-analysis of the literature was performed. A search of PubMed, Web of Science, Embase, and the Cochrane Library databases was conducted from inception through December 2023 and updated in February 2024. Search terms included laminoplasty, laminectomy, C3 and degenerative cervical spondylosis. The literature search yielded 14 studies that met our inclusion criteria. Outcomes included radiographic results, neck pain, neurologic function, surgical parameters, and postoperative complications. We also assessed methodologic quality, publication bias, and quality of evidence. RESULTS: Fourteen studies were identified, including 590 patients who underwent LP combined with C3 LN (modified group, MG) compared to 669 patients who underwent LP (traditional group, TG). The results of the study indicated a statistically significant improvement in cervical range of motion (WMD = 3.62, 95% CI: 0.39 to 6.85) and cervical sagittal angle (WMD = 2.07, 95% CI: 0.40 to 3.74) in the MG compared to the TG at the last follow-up (very low-level evidence). The TG had a higher number of patients with complications, especially C2-3 bone fusion. There was no significant difference found in improvement of neck pain, JOA, NDI, cSVA, T1 slope at latest follow-up. CONCLUSION: LP combined with C3 LN is an effective and necessary surgical method for multilevel DCM patients to maintain cervical sagittal balance. However, due to the low quality of evidence in existing studies, more and higher quality research on the technology is needed in the future.

Transient Interference Excision and Spectrum Reconstruction with Partial Samples Using Modified Alternating Direction Method of Multipliers-Net for the Over-the-Horizon Radar.

Transient interference often submerges the actual targets when employing over-the-horizon radar (OTHR) to detect targets. In addition, modern OTHR needs to carry out multi-target detection from sea to air, resulting in the sparse sampling of echo data. The sparse OTHR signal will raise serious grating lobes using conventional methods and thus degrade target detection performance. This article proposes a modified Alternating Direction Method of Multipliers (ADMM)-Net to reconstruct the target and clutter spectrum of sparse OTHR signals so that target detection can be performed normally. Firstly, transient interferences are identified based on the sparse basis representation and then excised. Therefore, the processed signal can be seen as a sparse OTHR signal. By solving the Doppler sparsity-constrained optimization with the trained network, the complete Doppler spectrum is reconstructed effectively for target detection. Compared with traditional sparse solution methods, the presented approach can balance the efficiency and accuracy of OTHR signal spectrum reconstruction. Both simulation and real-measured OTHR data proved the proposed approach's performance.

Prognostic factors and outcomes of surgical intervention for patients with spinal metastases secondary to lung cancer: an update systematic review and meta analysis.

PURPOSE: Lung cancer is one of the most common malignant tumors. Most patients develop spinal metastases during the course of cancer and suffer skeletal-related events. Currently, no consensus has been reached on the prognostic factors in patients undergoing surgeries. This study aimed to answer two questions: (1) what are the effects of surgical intervention, and (2) what are the factors associated with postoperative survival. METHODS: Searches were performed on electronic databases including PubMed, Ovid/MEDLINE, Cochrane, and Scopus for articles published before February of 2022, involving the survival factors of patients with spinal metastasis. Multiple data items were considered, such as baseline demographics, surgical details, clinical outcome, and prognostic factors. The analysis was performed in Review Manager (RevMan) 5.5. The prognostic factors of survival were analyzed with univariate and multivariate cox regression analysis. RESULTS: Finally, 14 studies with 813 patients were identified. Their 6, 12, and 24 months survival rates ranged from 18 to 58%, 18 to 22.4%, and 0 to 58.5%, respectively. The pooled hazard ratio of preoperative ambulatory status and the number of involved vertebrae demonstrated statistical significance, while no significant prognostic effect on the overall survival was found for targeted therapy, visceral metastases, chemotherapy, radiotherapy, or postoperative ambulatory status. CONCLUSION: Overall, surgical intervention could achieve significant pain relief and neurological function improvements. For patients receiving surgery for spinal metastasis from lung cancer, preoperative ambulatory status and the number of involved vertebrae were significant prognostic factors associated with their survival.

Pediatric meningioma with a Novel MAML2-YAP1 fusion variant: a case report and literature review.

BACKGROUND: Pediatric meningioma with YAP1 fusion is a rare subset of meningiomas. Currently, there are lack of integrated clinical, radiological, and pathological features on this subset. Here, we reported a case of pediatric meningioma with a novel MAML2-YAP1 fusion variant and reviewed the relevant literature. CASE PRESENTATION: We presented a case of 12-year-old boy with meningioma adjacent to the superior sagittal sinus and falx. Simpson grade II gross total resection was performed after diagnosis. Pathologically, he was diagnosed as WHO grade I meningothelial meningioma with rhabdoid features. A next-generation sequencing-based gene panel was performed to determine the molecular features for potential treatment, and a novel MAML2-YAP1 fusion break point was identified. CONCLUSION: Pediatric meningioma with the fusion of YAP1 and MAML2 genes is more likely to have pathological features of rhabdiod cells, which needs to be validated in large-scale studies for exploring better treatment under the integrated diagnosis.

Structural Determination of a Graphite/Hexagonal Boron Nitride Superlattice Observed in the Experiment.

A previous study reported an observed unidentified graphite/hexagonal boron nitride (hBN) superlattice structure in special multilayer heterojunction devices via cross-sectional transmission electron microscopy [Haigh S. J. et al., Nat. Mater. 2012, 11, 764-767]. In this letter, we designed and confirmed two possible graphite/hBN superlattice structures (AA and Ab), which were probably the structures observed by the aforementioned experiment. The formation enthalpies of both structures were negative, indicating that they could be successfully synthesized as the previous experiment reported. The results also showed that both structures possessed dynamic stability and elastic stability. Importantly, the theoretical interlayer distances of AA and Ab were 3.34 and 3.30 Å, respectively, which were consistent with the experimental value of 3.32 Å. The X-ray diffraction patterns and Raman spectra of both structures were simulated to aid in distinguishing them. This study on the atomic structure of the graphite/hBN superlattice lays a foundation for further research and application of this material.

Cascade Oxidative C-H Annulation of Thiophenes: Heck-Type Pathway Enables Concise Access to Thienoacenes.

The pursuit of efficient synthetic route to thienoacenes represents an appealing yet challenging task in the fields of both organic synthetic chemistry and organic functional materials. In this work, we disclose a rhodium-catalyzed cascade C-H annulation of phenacyl phosphoniums with (benzo)thiophenes via a Heck-type pathway to provide a new class of planar thienoacenes, which involves the formation of three Caryl -Caryl bonds and one Caryl -O bond in a single operation. The neutral S,O-heteroacenes exhibit superior stability and adopt a herringbone-like packing mode with efficient π-π stacking in the crystals, suggesting their potential in organic semiconducting materials. This work first exemplifies the superiority of cascade oxidative C-H annulation involving a Heck-type pathway in the development of concise access to heteroacenes.

Carrier-Free Platinum Nanomedicine for Targeted Cancer Therapy.

Numerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs; however, the complexities in carrier materials and functional integration make it challenging to promote these candidates for clinical translation. In this study, a facile method to prepare carrier-free anticancer nanodrug with inherent bone targeting and osteoclastogenesis inhibition capabilities is reported. Phytic acid, a naturally occurring and nontoxic product, is reacted with cisplatin to form uniform nanoparticles of different sizes. The prepared nanoparticles possess high drug loading and pH-responsive drug release behaviors. Phytic acid in the nanomedicine ensures high bone targeting and osteoclastogenesis inhibition, and the released platinum drugs triggered by tumor extracellular acidity eradicate tumor cells. The nanomedicine around 100 nm shows high anticancer activity and much reduced side effects in a subcutaneous breast cancer model when compared with cisplatin. In addition, it shows high accumulation at osteolytic lesions, and efficiently inhibits tumor growth and tumor-associated osteolysis in a bone metastatic breast cancer model. Here, a facile and efficient strategy to prepare carrier-free nanomedicines with high anticancer drug loading, inherent bone targeting, and osteoclast inhibitory activities for cancer therapy is provided.

Noninvasive prenatal detection of hemoglobin Bart hydrops fetalis via maternal plasma dispensed with parental haplotyping using the semiconductor sequencing platform.

BACKGROUND: Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE: In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN: In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS: As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION: Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.

GREM1 overexpression inhibits proliferation, migration and angiogenesis of osteosarcoma.

Osteosarcoma is the most common malignancy of bone that occurs in young adults and children, with a five-year survival rate of 60-70%. Metastasis of osteosarcoma maintains an even poorer prognosis. GREM1 plays an important role in regulating organogenesis, body patterning, and tissue differentiation. However, there are limited studies on GREM1 in osteosarcomas. This study was carried out to characterize the expression and function of GREM1 in osteosarcoma cells, thus extending our understanding of osteosarcoma metastasis. GREM1 expression was detected in hBMSC, hFOB1.19, Saos-2, MG63 and U2OS cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Gain- and loss-of-function approaches were used to assess the biological function of GREM1 in U2OS cells. The effects of GREM1 on U2OS cell proliferation were examined using the CCK-8 and colony formation assay. Migration and invasion ability were confirmed by the wound healing and Transwell assay, respectively. Flow cytometry was used to analyse the effect of GREM1 on the cell cycle and apoptosis. The expression of GREM1 targets was evaluated by qRT-PCR and western blotting. The expression of GREM1 was significantly downregulated in osteosarcoma. GREM1 overexpression inhibited the proliferation, migration and invasion of U2OS cells. GREM1 overexpression suppressed tumour cell-induced endothelial cell migration and invasion ability. The effect of GREM1 may be transduced through regulation of the BMP target transcription factor inhibitor of MMP-2 and -9 as well as Id1. GREM1 overexpression and knockdown regulates the tumorigenesis of osteosarcoma in vivo. In conclusion, GREM1 is downregulated in osteosarcoma cells, and overexpression of GREM1 inhibits the proliferation, migration, invasion and angiogenesis abilities of osteosarcoma cells in vitro and in vivo.

Nanotwinned diamond with unprecedented hardness and stability.

Although diamond is the hardest material for cutting tools, poor thermal stability has limited its applications, especially at high temperatures. Simultaneous improvement of the hardness and thermal stability of diamond has long been desirable. According to the Hall-Petch effect, the hardness of diamond can be enhanced by nanostructuring (by means of nanograined and nanotwinned microstructures), as shown in previous studies. However, for well-sintered nanograined diamonds, the grain sizes are technically limited to 10-30 nm (ref. 3), with degraded thermal stability compared with that of natural diamond. Recent success in synthesizing nanotwinned cubic boron nitride (nt-cBN) with a twin thickness down to ∼3.8 nm makes it feasible to simultaneously achieve smaller nanosize, ultrahardness and superior thermal stability. At present, nanotwinned diamond (nt-diamond) has not been fabricated successfully through direct conversions of various carbon precursors (such as graphite, amorphous carbon, glassy carbon and C60). Here we report the direct synthesis of nt-diamond with an average twin thickness of ∼5 nm, using a precursor of onion carbon nanoparticles at high pressure and high temperature, and the observation of a new monoclinic crystalline form of diamond coexisting with nt-diamond. The pure synthetic bulk nt-diamond material shows unprecedented hardness and thermal stability, with Vickers hardness up to ∼200 GPa and an in-air oxidization temperature more than 200 °C higher than that of natural diamond. The creation of nanotwinned microstructures offers a general pathway for manufacturing new advanced carbon-based materials with exceptional thermal stability and mechanical properties.

Isolation, X-ray crystal structure of the new diterpene and identification of others lignans and flavonoids from the fresh needles of Pinus massoniana.

Three new compounds, namely massonside C (1), massonianoside F (2), and 3, 8-dimethyl- herbacetin-7-O-ß-D-glucopyranoside (3), together with five known compounds (4-8), were isolated from the fresh needles of Pinus massoniana. Their structures were established by 1D, 2D NMR, HRMS and comparison with the literature data. The absolute configuration of 1 was confirmed by a combination of X-ray single crystal analysis. All isolated compounds were evaluated for the protective effect of human umbilical vein endothelial cells against oxidative damage.

EWS-FLI1-mediated tenascin-C expression promotes tumour progression by targeting MALAT1 through integrin α5ß1-mediated YAP activation in Ewing sarcoma.

BACKGROUND: The extracellular matrix has been critically associated with the tumorigenesis and progression of Ewing sarcoma (ES). However, the regulatory and prognostic roles of tenascin-C (TNC) in ES remain unclear. METHODS: TNC expression was examined in specimens by immunohistochemistry, and the association of TNC expression with ES patient survival was also analysed. TNC-knockout cell lines were constructed using CRISPR/Cas9 methods. In vitro experiments and in vivo bioluminescent imaging using BALB/c nude mice were conducted to evaluate the effect of TNC on ES tumour progression. RNA sequencing was performed, and the underlying mechanism of TNC was further explored. RESULTS: TNC was overexpressed in ES tissue and cell lines, and TNC overexpression was associated with poor survival in ES patients. TNC enhanced cell proliferation, migration and angiogenesis in vitro and promoted ES metastasis in vivo. The oncoprotein EWS-FLI1 profoundly increased TNC expression by directly binding to the TNC promoter region. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) upregulation induced by Yes-associated protein (YAP) activation was responsible for TNC-regulated ES tumour progression. Activated integrin α5ß1 signalling might be correlated with YAP dephosphorylation and nuclear translocation. CONCLUSIONS: TNC may promote ES tumour progression by targeting MALAT1 through integrin α5ß1-mediated YAP activation.

Clinical significance of traditional clinical parameters and inflammatory biomarkers for the prognosis of patients with spinal chondrosarcoma: a retrospective study of 150 patients in a single center.

BACKGROUND: To investigate the clinical significance of five inflammatory biomarkers and conventional clinical parameters in prognostic prediction of spinal chondrosarcoma. METHODS: Univariate and multivariate analyses were performed to investigate independent prognostic factors for recurrence and death of patients with spinal chondrosarcoma. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier curve, and differences were analyzed by log-rank test. The optimal cutoff values for NLR, PLR, LMR, and CAR were determined by X-tile program. RESULTS: The optimal cutoff value for NLR, PLR, LMR, AGR, and CAR was 2.7, 200, 3.0, 1.5, and 0.2, respectively. Of the 150 patients included, recurrence was detected in 105 patients, and death occurred in 78 patients. Multivariate analysis indicated that Tomita I-III, total resection, and CAR < 0.2 were significantly associated with longer DFS. Meanwhile, preoperative Frankel score D-E, total resection, and CAR < 0.2 were favorable prognostic factors for OS. Subtype analysis showed that only total resection was an independent prognostic factor for DFS of recurrent spinal chondrosarcoma. CONCLUSION: Total resection could significantly reduce the recurrence rate of spinal chondrosarcoma and improve OS of chondrosarcoma patients. Tomita classification I-III was a favorable factor for DFS, and preoperative Frankel score A-C was an adverse prognostic factor for OS. CAR was the most robust prognostic indicator with a discriminatory ability as compared with other inflammatory indicators. These slides can be retrieved under Electronic Supplementary Material.

Development of a novel model for predicting survival of patients with spine metastasis from colorectal cancer.

OBJECTIVE: To develop a novel nomogram for predicting survival of patients with spine metastasis from colorectal cancer (SMCRC) based on the clinical characteristics and prognostic factors. METHODS: Included in this study were 93 SMCRC patients who received treatments in our institute between 2006 and 2017, whose clinical data were analyzed retrospectively by univariate and multivariate analysis to identify independent variables that could predict prognosis. A nomogram for survival prediction was established on the basis of preoperative independent factors, and then subjected to bootstrap re-samples for internal validation. The discrimination was measured by concordance index (C-index). We used ROC analysis with the corresponding AUROC to compare the prediction accuracy of Changzheng Nomogram with three existing prognostic systems (Tomita, Tokuhashi and Bauer). RESULTS: The high and median degrees of primary tumor differentiation, primary tumor surgery, carcinoembryonic antigen ≤ 5 ng/ml, no visceral metastases and ECOG-PS (0-2) were favorable prognostic factors for CRC metastases in the spine. These five preoperative independent factors were identified and entered into the nomogram with the C-index of 0.786 (0.739-0.833). The calibration curves for probability of 12- and 24-month overall survival (OS) showed good agreement between the predictive risk and the actual risk, and calibration was assessed. Compared with the previous prognostic systems, Changzheng Nomogram reported in this study showed higher accuracy in predicting OS of patients with SMCRC spinal metastases (p < 0.05). CONCLUSION: By using this novel predictive model, clinicians could more precisely estimate the survival outcome of individual patients by evaluating clinical characteristics and identify subgroups of patients who are in need of a specific individual treatment strategy. These slides can be retrieved under Electronic Supplementary Material.

Methyl Helicterate Inhibits Hepatic Stellate Cell Activation Through Modulation of Apoptosis and Autophagy.

BACKGROUND/AIMS: Activated hepatic stellate cells (HSCs) are the major source of extracellular matrix (ECM). Therefore inhibiting HSC activation is considered as an effective strategy to inhibit the process of liver fibrosis. This study aimed to investigate the underlying mechanism of methyl helicterate (MH) isolated from Helicteres angustifolia on the activation of HSCs. METHODS: HSC-T6 cells were treated with various concentration of MH and autophagy was inhibited by 3-Methyl adenine (3-MA) or RNA interference. Cell viability was observed by MTT assay and cell colony assay. Cell cycle and apoptosis were analyzed using flow cytometry. Autophagic vacuoles were observed by transmission electron microscopy and monodansyl cadaverine (MDC) staining. Moreover, autophagy-related genes and proteins were detected using real-time PCR and Western blot assays, respectively. RESULTS: MH significantly inhibited HSC activation, as evidenced by the inhibition of cell viability, colony formation and the expression of α-SMA and collagen I. MH caused cell cycle arrest in G2/M phase. Moreover, MH significantly induced apoptosis through regulating the mitochondria-dependent pathway and the activity of caspases. MH treatment significantly increased lysosomes and autophagosomes, and enhanced the formation of autophagic vacuoles and autophagic flux. Interestingly, inhibiting autophagy by 3-MA or RNA interference abolished the ability of MH in inhibiting HSC activation. On the other hand, induction of autophagy promoted MH-induced HSC apoptosis. Further study showed that MH-induced HSC apoptosis and autophagy was mediated by the JNK and PI3K/Akt/mTOR pathways. CONCLUSION: Our results demonstrate that MH-induced HSC apoptosis and autophagy may be one of the important mechanisms for its anti-fibrosis effect.

Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA.

Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer.