Higher serum carotenoid concentrations were associated with the lower risk of cancer-related death: Evidence from the National Health and Nutrition Examination Survey.

The study focuses on the association between serum carotenoids and cancer-related death. Using data from the National Health and Nutrition Examination Survey (2001-2006 and 2017-2018), the study encompasses 10,277 participants older than age 20 years, with recorded baseline characteristics and serum carotenoid concentrations (including α-carotene, trans-ß-carotene, cis-ß-carotene, ß-cryptoxanthin, trans-lycopene, and lutein/zeaxanthin). We hypothesized that serum carotenoid concentrations were negatively associated with cancer-related death. The weighted chi-square analyses indicate significant negative correlations between higher serum concentrations of α-carotene, ß-cryptoxanthin, trans-lycopene, and total carotenoids, and the risk of cancer-related deaths. Using weighted Cox regression analysis, this study confirms that α-carotene, ß-cryptoxanthin, trans-lycopene, and total carotenoids, as continuous or categorical variables, are inversely related to cancer mortality (P < .0001). Furthermore, considering competitive risk events, lower concentrations of serum ß-cryptoxanthin (Fine-Gray P = 1.12e-04), trans-lycopene (P = 5.68e-14), and total carotenoids (P = .03) are associated with an increased risk of cancer-related deaths. The research reveals a crucial inverse relationship between serum carotenoid concentrations and cancer-related death.

Dual-exposure temporal laser speckle imaging for simultaneously accessing microvascular blood perfusion and angiography.

Laser speckle contrast imaging (LSCI) has gained significant attention in the biomedical field for its ability to map the spatio-temporal dynamics of blood perfusion in vivo. However, LSCI faces difficulties in accurately resolving blood perfusion in microvessels. Although the transmissive detecting geometry can improve the spatial resolution of tissue imaging, ballistic photons directly transmitting forward through tissue without scattering will cause misestimating in the flow speed by LSCI because of the lack of a quantitative theoretical model of transmissvie LSCI. Here, we develop a model of temporal LSCI which accounts for the effect of nonscattered light on estimating decorrelation time. Based on this model, we further propose a dual-exposure temporal laser speckle imaging method (dEtLSCI) to correct the overestimation of background speed when performing traditional transmissive LSCI, and reconstruct microvascular angiography using the scattered component extracted from total transmitted light. Experimental results demonstrated that our new method opens an opportunity for LSCI to simultaneously resolve the blood vessels morphology and blood flow speed at microvascular level in various contexts, ranging from the drug-induced vascular response to angiogenesis and the blood perfusion monitoring during tumor growth.

Knowledge, attitude, and practice of lung cancer screening and associated factors among high-risk population in Lanzhou, China: A cross-sectional study.

This study aimed to assess the knowledge, attitude, and practice (KAP) of high-risk populations toward lung cancer screening in Lanzhou, China. Using convenience sampling, this cross-sectional study enrolled outpatients at high-risk for lung cancer at Lanzhou University Second Hospital between November 2022 and March 2023. An anonymous, self-administered online questionnaire was distributed to each participant via the Sojump website (https://www.wjx.cn/), comprising 40 items to collect demographic information and evaluate KAP toward lung cancer screening. The analyses were descriptive. A total of 577 participants (average age of 61.8 ±â€…7.1 years; 306 males) were included in the study. The participants' scores for KAP were 4.9 ±â€…2.2, 27.4 ±â€…3.0, and 7.0 ±â€…2.1, respectively. Participants with occupational exposure had significantly lower knowledge score (3.3 ±â€…2.4 vs 5.2 ±â€…2.1, P < .001), and practice score (5.6 ±â€…2.4 vs 7.3 ±â€…1.9, P < .001) than those without occupational exposure. Participants with smoking or passive smoking history had significantly higher attitude scores (27.6 ±â€…2.9 vs 25.8 ±â€…3.2, P < .001) and practice scores (7.1 ±â€…2.0 vs 6.5 ±â€…2.5, P = .014) than those without smoking history. A total of 360 (62.4%) participants endorsed the doctors' counseling on lung cancer screening, and 355 (61.5%) participants were willing to have screening for lung cancer as doctors advised. The study revealed that 390 (67.6%) participants identified low-dose computed tomography as the appropriate method for lung cancer screening, while 356 (61.7%) participants believed that X-rays were a reliable screening method for lung cancer. However, 365 (63.3%) participants thought that the treatment outcomes for early and late-diagnosed lung cancer were the same. Additionally, 416 (72.10%) participants believed that annual lung cancer CT scanning is unnecessary. On the other hand, 339 (58.8%) participants expressed concerns about exposure to radiation from CT scans, while 349 (60.5%) participants were worried about the cost of lung cancer screening. Only 142 (24.6%) participants reported having undergone annual lung cancer screening. The high-risk population had limited knowledge and insufficient attitude and practice toward lung cancer screening in Lanzhou, China.

A prognostic nomogram based on least absolute shrinkage and selection operator Cox regression in patients with pulmonary large-cell neuroendocrine carcinoma.

Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of breast cancer with a poor prognosis. Despite its rarity, it is important to gain a better understanding of the epidemiological, clinical, and prognostic features of pulmonary LCNEC. The purpose of this study was to design, construct, and validate a new nomogram for predicting overall survival (OS) in patients with pulmonary LCNEC. Methods: In total, the data of 1,864 LCNEC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, which is maintained by the National Cancer Institute in the United States and serves as a comprehensive source of cancer-related information. Of these patients, 556 served as the validation group and 1,308 served as the training cohort. We constructed a new nomogram with the training cohort that included the independent factors for OS as identified by least absolute shrinkage and selection operator Cox regression. Five independent factors were ultimately selected by the stepwise regression. Every factor of the Cox regression was included in the nomogram. Analyses of the calibration curve, decision curve, area under the curve, and concordance index (C-index) values were performed to assess the effectiveness and discriminative ability of the nomogram. Results: Five optimal predictive factors for OS were selected and merged to construct a 3- and 5-year OS nomogram. The nomogram had C-index values of 0.716 and 0.708 in the training cohort and validation cohort, respectively. The actual OS rates and the calibration curves showing the predictions of the nomogram were in good agreement. Conclusions: The prognostic nomogram may be very helpful in estimating the OS of patients with pulmonary LCNEC.

Integration of bulk RNA sequencing to reveal protein arginine methylation regulators have a good prognostic value in immunotherapy to treat lung adenocarcinoma.

Background: Given the differential expression and biological functions of protein arginine methylation (PAM) regulators in lung adenocarcinoma (LUAD), it may be of great value in the diagnosis, prognosis, and treatment of LUAD. However, the expression and function of PAM regulators in LUAD and its relationship with prognosis are unclear. Methods: 8 datasets including 1798 LUAD patients were selected. During the bioinformatic study in LUAD, we performed (i) consensus clustering to identify clusters based on 9 PAM regulators related expression profile data, (ii) to identify hub genes between the 2 clusters, (iii) principal component analysis to construct a PAM.score based on above genes, and (iv) evaluation of the effect of PAM.score on the deconstruction of tumor microenvironment and guidance of immunotherapy. Results: We identified two different clusters and a robust and clinically practicable prognostic scoring system. Meanwhile, a higher PAM.score subgroup showed poorer prognosis, and was validated by multiple cohorts. Its prognostic effect was validated by ROC (Receiver operating characteristic curve) curve and found to have a relatively good prediction efficacy. High PAM.score group exhibited lower immune score, which associated with an immunosuppressive microenvironment in LUAD. Finally, patients exhibiting a lower PAM.score presented noteworthy therapeutic benefits and clinical advantages. Conclusion: Our PAM.score model can help clinicians to select personalized therapy for LUAD patients, and PAM.score may act a part in the development of LUAD.

Metagenomic next-generation sequencing to investigate infectious keratitis by Corynespora cassiicola: a case report.

In this report, the case of a 65-year-old immunosuppressed female who presented with recurring redness and irritation in her right eye for 2 months is described. Ocular examination revealed conjunctival congestion, feather-like greyish-white corneal deep stromal infiltrate, white, floccular material sprawling from the anterior chamber angle and hypopyon. The in vivo confocal microscopy (IVCM) instantly confirmed fungal keratitis, and empirical antifungal therapy was thus administered. The patient exhibited therapeutic penetrating keratoplasty, however, due to the progression of infection and the lack of identified pathogens. The fungal isolate was identified as Corynespora cassiicola by metagenomic next-generation sequencing (mNGS) of the host cornea. The patient responded well to intensive conservative therapy and subsequent surgical therapy. To our knowledge, this case represents the first case of C. cassiicola infection from China, highlighting the emergence of a rare fungus that causes keratitis. Furthermore, mNGS has the capability to facilitate prompt identification and timely management of challenging ocular infections that are difficult to diagnose.

Study on a performance matching method of wind rotor and generator based on energy transfer.

Wind power systems are a promising form of energy supply. At present, most of the studies focuses on the performance of individual components such as wind rotors or generators, and the overall output effect of wind power system is determined by the characteristics of wind rotor and generator and their combined characteristics. However, the evaluation of the overall output characteristics of the system is rarely considered. In order to investigate the overall output of the system quickly, a performance matching method of wind rotor and generator based on energy transfer is proposed in this paper. Based on the series operating characteristics of the wind power system model, the energy transformation process of the wind rotor, generator and the whole system are unified described by energy transfer. On the premise that the performance of wind rotor and generator is known, the transfer function model of each component is established, and on this basis, the transfer function model of the overall system is obtained. Then, the overall output effect of the system is analyzed and evaluated by this system transfer function model. The performance of the model is analyzed and compared by using a vertical axis wind power system coupling test bench and MATLAB/Simulink software. The results show that the error between the system output based on the theoretical model and the wind tunnel test is less than 6.5%, and the trend of the simulation and the test curve of the system output is consistent. Therefore, this method can be used to quickly predict the overall output performance of the wind turbine and generator on the premise that the performance of each component is known, without the need to connect each component to a wind power system for testing.

"Domino" cascade reactor based on DNA hydrogel for synergistic treatment of malignant tumor.

The action pathways of starvation therapy and photodynamic therapy (PDT) do not exist in isolation and are usually related to tumor cell metabolism and immune regulation, which are of great significance in the treatment of malignant tumors. Here, a cancer-targeted "domino" cascade reactor is constructed for synergistic starvation therapy and amplifies photodynamic therapy by assembling hemin and glucose oxidase (GOx) into DNA hydrogel load with hypoxia-inducible factor 1α (HIF-1α) and photosensitizer chlorin e6 (Ce6). The cascade reactor has excellent biocompatibility and tumor targeting, which promotes PDT by reducing HIF-1α. At the same time, the G-quadruplex of AS1411 combined with hemin (AH) catalyzes the generation of oxygen from hydrogen peroxide to further improve the efficiency of PDT. The synergistic therapeutic effect of the cascade reactor is evaluated through in vivo and in vitro experiments, indicating that this cascade reactor has great potential advantages in the synergistic treatment of cancer.

Repurposing nitazoxanide as a novel anti-atherosclerotic drug based on mitochondrial uncoupling mechanisms.

BACKGROUND AND PURPOSE: The anthelmintic drug nitazoxanide has a mitochondrial uncoupling effect. Mitochondrial uncouplers have been proven to inhibit smooth muscle cell proliferation and migration, inhibit NLRP3 inflammasome activation of macrophages and improve dyslipidaemia. Therefore, we aimed to demonstrate that nitazoxanide would protect against atherosclerosis. EXPERIMENTAL APPROACH: The mitochondrial oxygen consumption of cells was measured by using the high-resolution respirometry system, Oxygraph-2K. The proliferation and migration of A10 cells were measured by using Edu immunofluorescence staining, wound-induced migration and the Boyden chamber assay. Protein levels were measured by using the western blot technique. ApoE (-/-) mice were fed with a Western diet to establish an atherosclerotic model in vivo. KEY RESULTS: The in vitro experiments showed that nitazoxanide and tizoxanide had a mitochondrial uncoupling effect and activated cellular AMPK. Nitazoxanide and tizoxanide inhibited serum- and PDGF-induced proliferation and migration of A10 cells. Nitazoxanide and tizoxanide inhibited NLRP3 inflammasome activation in RAW264.7 macrophages, the mechanism by which involved the AMPK/IκBα/NF-κB pathway. Nitazoxanide and tizoxanide also induced autophagy in A10 cells and RAW264.7 macrophages. The in vivo experiments demonstrated that oral administration of nitazoxanide reduced the increase in serum IL-1ß and IL-6 levels and suppressed atherosclerosis in Western diet-fed ApoE (-/-) mice. CONCLUSION AND IMPLICATIONS: Nitazoxanide inhibits the formation of atherosclerotic plaques in ApoE (-/-) mice fed on a Western diet. In view of nitazoxanide being an antiprotozoal drug already approved by the FDA, we propose it as a novel anti-atherosclerotic drug with clinical translational potential.

Correction to "Novel long non-coding RNA LINC02532 promotes gastric cancer cell proliferation, migration, and invasion in vitro".

[This corrects the article on p. 91 in vol. 11, PMID: 30788037.].

Drug-Induced Self-Assembly Cascade Nanoreactor for Synergistic Tumor Therapy.

The construction of completely biocompatible and biodegradable tumor suppressors by a simple and reliable method is essential for the clinical application of cancer-targeted drugs. Herein, by inserting glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) into human serum albumin (HSA) assembly molecules, we constructed a cancer-targeted cascade bioreactor for synergistic starvation and photodynamic therapy (PDT). The modification of HSA could block the GOx activity and reduce the cytotoxicity of normal cells and organs. Through active targeting and passive enhanced permeability and retention effect, the loading of AS1411 could promote the cascade bioreactors to effectively target nucleolin-overexpressed tumors. Once internalized by cancer cells, as a result of catalyzing hydrogen peroxide (H2O2) to produce oxygen (O2), the protein nano-cascade reactor promoted microenvironmental oxygenation, which would subsequently lead to an increase in cytotoxic singlet oxygen (1O2) production under light irradiation as well as the decomposition of intracellular glucose. In vitro and in vivo studies showed that the cascaded nanoreactors could significantly enhance therapeutic efficacy through synergistic starvation therapy and enhanced PDT as well as chemotherapy. This cascade strategy will be demonstrated in clinical applications with huge potential.

Porous geopolymer with controllable interconnected pores-a viable permeable reactive barrier filler for lead pollutant removal.

Most of the commonly used traditional permeable reactive barrier (PRB) fillers have many drawbacks, such as poor retention of hydraulic conductivity, high cost, and a complex preparation process. Porous geopolymers (PGPs) with controllable pore structures could circumvent these drawbacks owing to their high adsorption capacity, cost-effective synthesis, and good chemical stability. In this study, based on our previous research, the "foaming-liquid film" balance control method was proposed and used to fabricate three PGPs with gradient pore connectivity. The influence of pore structure on the Pb2+ removal performance and migration mechanism were investigated by conducting both batch and column experiments. Closed, dead-end, capillary, and interconnected pores exist in the PGPs, and results indicated that interconnected pores effectively promote the migration of solute in the main flow channels to the deeper matrix, thereby enhancing the long-term dynamic removal efficiency. At breakthrough, the Pb2+ uptake of PGP-3 reached 146 mg g-1. Further, the proposed "foaming-liquid film" balance control method is effective to prepare PGPs with controllable connectivity, and the PGP-PRBs with a high proportion of interconnected pores exhibit excellent performance for the removal of heavy metals, which is advantageous for their future applications in groundwater decontamination.

Apoptosis-Related Gene-Mediated Cell Death Pattern Induces Immunosuppression and Immunotherapy Resistance in Gastric Cancer.

Background: Apoptosis is a type of cell death, which can produce abundant mediators to modify the tumor microenvironment. However, relationships between apoptosis, immunosuppression, and immunotherapy resistance of gastric cancer (GC) remain unclear. Methods: Gene expression data and matching clinical information were extracted from TCGA-STAD, GSE84437, GSE34942, GSE15459, GSE57303, ACRG/GSE62254, GSE29272, GSE26253, and IMvigor210 datasets. A consensus clustering analysis based on six apoptosis-related genes (ARGs) was performed to determine the molecular subtypes, and then an apoptosisScore was constructed based on differentially expressed and prognostic genes between molecular subtypes. Estimate R package was utilized to calculate the tumor microenvironment condition. Kaplan-Meier analysis and ROC curves were performed to further confirm the apoptosisScore efficacy. Results: Based on six ARGs, two molecular subgroups with significantly distinct survival and immune cell infiltration were identified. Then, an apoptosisScore was built to quantify the apoptosis index of each GC patient. Next, we investigated the correlations between the clinical characteristics and apoptosisScore using logistic regression. Multivariate Cox analysis shows that low apoptosisScore was an independent predictor of poor overall survival in TCGA and ACRG datasets, and was associated with the higher pathological stage. Meanwhile, low apoptosisScore was associated with higher immune cell, higher ESTIMATEScore, higher immuneScore, higher stromalScore, higher immune checkpoint, and lower tumorpurity, which was consistent with the "immunity tidal model theory". Importantly, low apoptosisScore was sensitive to immunotherapy. In addition, GSEA indicated that several gene ontology and Kyoto Encyclopedia of Genes and Genomes items associated with apoptosis, several immune-related pathways, and JAK-STAT signal pathway were considerably enriched in the low apoptosisScore phenotype pathway. Conclusion: Our findings propose that low apoptosisScore is a prognostic biomarker, correlated with immune infiltrates, and sensitivity to immunotherapy in GC.

A novel 8-genome instability-associated lncRNAs signature predicting prognosis and drug sensitivity in gastric cancer.

BACKGROUND: Genome instability lncRNA (GILnc) is prevalently related with gastric cancer (GC) pathophysiology. However, the study on the relationship GILnc and prognosis and drug sensitivity of GC remains scarce. METHOD: We extracted expression data of 375 GC patients from TCGA cohort and 205 GC patients from GSE26942 cohort. Then, lncRNA was separated from expression data, and systematically characterized the 8 marker lncRNAs using the LASSO method. Next, we constructed a GILnc model (GILnc score) to quantify the GILnc index of each GC patient. Finally, we analyzed the relationship between GILnc score and clinical traits including survival outcomes, TP53, and drug sensitivity of GC. RESULTS: Based on a computational frame, 205 GILncs in GC has been identified. Then, a 8 GILncs was successfully established to predict overall survival in GC patients based on LASSO analysis, divided GC samples into high GILnc score and low GILnc score groups with significantly different outcome and was validated in multiple independent patient cohorts. Furthermore, GILnc model is better than the prediction performance of two recently published lncRNA signatures, and the high GILnc score group was more sensitive to mitomycin. Besides, the GILnc score has greater prognostic significance than TP53 mutation status alone and is capable of identifying intermediate subtype group existing with partial TP53 functionality in TP53 wild-type patients. Finally, GILnc signature as verified in GSE26942. CONCLUSION: We applied bioinformatics approaches to suggest that a 8 GILnc signature could serve as prognostic biomarkers, and provide a novel direction to explore the pathogenesis of GC.

Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice.

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe -/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

Temporal trends of heavy metals in the sediments of Bohai Bay in China.

The status and trend of mercury (Hg), cadmium (Cd), lead (Pb), copper (Cu), chromium (Cr), zinc (Zn), and arsenic (As) in the sediment of Bohai Bay from 1978 to 2017 were evaluated. The results indicated that the sediment status in 2017 was good. The contents of Hg, Cd, Pb, Cu, Cr, Zn, and As in all the monitoring stations were lower than category I. But, it is worth noting that the contents of Cu, Cr, and As in some stations were between threshold effects levels (TEL) and probable effects levels (PEL) guidelines, which were occasionally correlated to negative ecological effects. Since the reform and opening up of China, only the average content of Cd in 1996 was between category II and category III, but that in other years did not exceed category I. The average contents of Hg, Pb, Cu, Cr, Zn, and As were lower than category I. The Chinese Government should continue to pay high attention to the total quantity control measures of major risk factors Cd, Cu, Cr, and As.

Anthelmintic niclosamide attenuates pressure-overload induced heart failure in mice.

The heart is a high energy demand organ and enhancing mitochondrial function is proposed as the next-generation therapeutics for heart failure. Our previous study found that anthelmintic drug niclosamide enhanced mitochondrial respiration and increased adenosine triphosphate (ATP) production in cardiomyocytes, therefore, this study aimed to determine the effect of niclosamide on heart failure in mice and the potential molecular mechanisms. The heart failure model was induced by transverse aortic constriction (TAC) in mice. Oral administration of niclosamide improved TAC-induced cardiac hypertrophy, cardiac fibrosis, and cardiac dysfunction in mice. Oral administration of niclosamide reduced TAC-induced increase of serum IL-6 in heart failure mice. In vitro, niclosamide within 0.1 µM increased mitochondrial respiration and ATP production in mice heart tissues. At the concentrations more than 0.1 µM, niclosamide reduced the increased interleukin- 6 (IL-6) mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 and THP-1 derived macrophages. In cultured primary cardiomyocytes and cardiac fibroblasts, niclosamide (more than 0.1 µM) suppressed IL-6- and phenylephrine-induced cardiomyocyte hypertrophy, and inhibited collagen secretion from cardiac fibroblasts. In conclusion, niclosamide attenuates heart failure in mice and the underlying mechanisms include enhancing mitochondrial respiration of cardiomyocytes, inhibiting collagen secretion from cardiac fibroblasts, and reducing the elevated serum inflammatory mediator IL-6. The present study suggests that niclosamide might be therapeutic for heart failure.

CHIR-99021 regulates mitochondrial remodelling via ß-catenin signalling and miRNA expression during endodermal differentiation.

Mitochondrial remodelling is a central feature of stem cell differentiation. However, little is known about the regulatory mechanisms during these processes. Previously, we found that a pharmacological inhibitor of glycogen synthase kinase-3α and -3ß, CHIR-99021, initiates human adipose stem cell differentiation into human definitive endodermal progenitor cells (hEPCs), which were directed to differentiate synchronously into hepatocyte-like cells after further treatment with combinations of soluble factors. In this study, we show that CHIR-99021 promotes mitochondrial biogenesis, the expression of PGC-1α (also known as PPARGC1A), TFAM and NRF1 (also known as NFE2L1), oxidative phosphorylation capacities, and the production of reactive oxygen species in hEPCs. Blocking mitochondrial dynamics using siRNA targeting DRP1 (also known as DNM1L) impaired definitive endodermal differentiation. Downregulation of ß-catenin (CTNNB1) expression weakened the effect of CHIR-99021 on the induction of mitochondrial remodelling and the expression of transcription factors for mitochondrial biogenesis. Moreover, CHIR-99021 decreased the expression of miR-19b-2-5p, miR-23a-3p, miR-23c, miR-130a-3p and miR-130a-5p in hEPCs, which target transcription factors for mitochondrial biogenesis. These data demonstrate that CHIR-99021 plays a role in mitochondrial structure and function remodelling via activation of the ß-catenin signalling pathway and inhibits the expression of miRNAs during definitive endodermal differentiation.This article has an associated First Person interview with the first author of the paper.

MiR-1236-3p serves as a new diagnostic and prognostic biomarker for gastric cancer.

BACKGROUND: The microRNA plays an important role in tumor progression. MiR-1236-3p acts as a tumor suppressor in various malignancies. OBJECTIVE: The aim of present study was to explore the expression of miR-1236-3p in gastric cancer (GC) and its correlation with clinicopathological features, and evaluate the feasibility of using it as a prognostic biomarker in GC. METHODS: Seventy-six pairs of tissue specimens were collected from GC patients. MiR-1236-3p expression level was detected by using qRT-PCR. The diagnostic value of miR-1236-3p was evaluated by receiver operating characteristic curve, and Kaplan-Meier method was used to analyze the overall survival. Prognosis analysis was performed using multivariate cox proportional hazards regression analysis. RESULTS: The expression of miR-1236-3p was significantly reduced in tumor tissues (P< 0.001). In addition, miR-1236-3p expression was correlated with TNM stage (P= 0.001), lymph node metastasis (P= 0.005) and differentiated degree (P= 0.001). The area under the curve was 0.7016, and its specificity and sensitivity were 60.53% and 73.68%. Kaplan-Meier survival curves showed that patients with high miR-1236-3p expression had better overall survival than those with low expression (P= 0.0190). Multivariate Cox regression analysis showed that the miR-1236-3p expression (P= 0.033) was an independent prognostic factor for overall survival of GC prognosis. CONCLUSIONS: The study showed that miR-1236-3p is downregulated in GC tissues, and low expression of miR-1236-3p is associated with a poor prognosis in GC. It may be a new diagnostic and prognostic biomarker for GC.

Conformation Search Across Multiple-Level Potential-Energy Surfaces (CSAMP): A Strategy for Accurate Prediction of Protein-Ligand Binding Structures.

Accurate protein binding structure determination presents a great challenge to both experiment and theory. Here, in this work, we propose a new DOX protocol which combines the ensemble molecular Docking as the coarse-level, structure Optimization with the semiempirical quantum mechanics methods as the medium level, and the eXtended ONIOM ( XO) calculations as the fine level. The fundamental of the DOX protocol relies on the Conformation Search Across Multiple-level Potential-energy surfaces (CSAMP) strategy, where the conformation spaces of a funnel-like structure are searched from the coarse level with hundreds of candidates to the medium level with around 10 top candidates to the fine level with the final top 1 or 2 binding modes. An in-depth test for the protocol set up against 28 crystallographic data consisting of HMGR-statins, SDase-inhibitors, 3HNRase-inhibitors, and NA-inhibitors yielded a satisfactory result with ∼0.5 Šroot-mean-square deviations (RMSDs) on geometries and ∼0.8 kcal/mol absolute error of relative binding energies on average. A further larger scale validation on the Astex test set (including 85 diverse structures) revealed an impressive performance with a RMSD < 2 Šsuccess rate of 99%, suggesting DOX is a promising computational route toward accurate prediction of the protein-ligand binding structures.