Author Correction: STEEP mediates STING ER exit and activation of signaling.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

STEEP mediates STING ER exit and activation of signaling.

STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signaling, the mechanism that drives this process is not understood. Here we identify STEEP as a positive regulator of STING signaling. STEEP was associated with STING and promoted trafficking from the ER. This was mediated through stimulation of phosphatidylinositol-3-phosphate (PtdIns(3)P) production and ER membrane curvature formation, thus inducing COPII-mediated ER-to-Golgi trafficking of STING. Depletion of STEEP impaired STING-driven gene expression in response to virus infection in brain tissue and in cells from patients with STING-associated diseases. Interestingly, STING gain-of-function mutants from patients interacted strongly with STEEP, leading to increased ER PtdIns(3)P levels and membrane curvature. Thus, STEEP enables STING signaling by promoting ER exit.

Causal association of sleep traits with the risk of thyroid cancer: A mendelian randomization study.

BACKGROUND: This study was to explore the causal associations of sleep traits including sleep duration, snoring, chronotype, sleep disorders, getting up in the morning, sleeplessness/insomnia and nap during day with the risk of thyroid cancer based on Mendelian randomization (MR) analysis. METHOD: Summary single nucleotide polymorphism (SNP)-phenotype association data were obtained from published genome-wide association studies (GWASs) using the FinnGen and UK Biobank databases. A series of screening processes were performed to select qualified SNPs strongly related to exposure. We applied the inverse variance weighted (IVW), the Mendelian Randomization robust adjusted profile score (MR-RAPS), the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and the Weighted Median to estimate the causal links between sleep traits and the risk of thyroid cancer. Odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: The IVW results showed that getting up in the morning (OR = 0.055, 95%CI: 0.004-0.741) and napping during day (OR = 0.031, 95%CI: 0.002-0.462) were associated with decreased risk of thyroid cancer in the Italian population. A 1.30-h decrease of sleep duration was associated with 7.307-fold of thyroid cancer risk in the Finnish population (OR = 7.307, 95%CI: 1.642-32.519). Cronotype could decrease the risk of thyroid cancer in the Finnish population (OR = 0.282, 95%CI: 0.085-0.939). Sleep disorders increased the risk of thyroid cancer in the Finnish population (OR = 2.298, 95%CI: 1.194-4.422). The combined results revealed that sleep duration was correlated with increased risk of thyroid cancer (OR = 5.600, 95%CI: 1.458-21.486). CONCLUSION: Decreased sleep duration was associated with increased risk of thyroid cancer, which indicated the importance of adequate sleep for the prevention of thyroid cancer.

Excellent ratiometric two-photon fluorescent probes for hydrogen sulfide detection based on the fluorescence resonance energy transfer mechanism.

Fluorescence resonance energy transfer (FRET) is an important mechanism to design ratiometric fluorescent probes that are able to detect analytes quantitatively according to the ratio of two well-resolved emission signals. Two-photon (TP) fluorescent probes can realize the detection in living cells and tissues with deeper penetration depth, higher resolution, and lower photodamage in contrast to one-photon fluorescent probes. However, to date, fabricating TP-FRET ratiometric fluorescent probes possessing large two-photon absorption (TPA), high fluorescence quantum yield and perfect FRET efficiency is still challenging. Consequently, to develop excellent TP-FRET ratiometric probes and explore the relationship between their molecular structures and TP fluorescence properties, in this paper, we designed a series of H2S-detecting TP fluorescent probes employing the FRET mechanism based on an experimental probe BCD. Thereafter, we comprehensively evaluated the TP sensing performance of these probes by means of time-dependent density functional theory and quadratic response theory. Furthermore, we determined energy transfer efficiency and fluorescence quantum yield. Significantly, through regulating benzene-fused positions, we successfully improved fluorescence quantum yield and TPA cross-section simultaneously. Large spectral overlap between energy donor emission and acceptor absorption was achieved and near perfect energy transfer efficiency was acquired for all the studied probes. We revealed that these probes exhibit two well-resolved TPA bands, which are contributed by FRET donors and acceptors, respectively. Especially, both the wavelengths and the cross-sections of the two TPA bands agree well with those of energy donors and acceptors, which is the unique TPA spectral profile of FRET probes and has never been previously reported. Moreover, we proposed an excellent TP-FRET probe BCD3 and its product molecule BCD3-H2S, which exhibit large Stokes (141 nm and 88 nm) and emission shifts (5931 cm-1), as well as greatly increased TP action cross-sections (24-fold and 60-fold) in the near-infrared region with respect to BCD and BCD-H2S. Our detailed study can give an insight into the efficient design of novel TP-FRET fluorescent probes.

Hypoxia expedites the progression of papillary thyroid carcinoma by promoting the CPT1A-mediated fatty acid oxidative pathway.

Hypoxia has been reported to promote the proliferation and migration of thyroid cancer, while the special mechanism was still unclear. HIF-1α/carnitine palmitoyl-transferase 1A (CPT1A) was found to be associated with papillary thyroid carcinoma (PTC) but the biological role of CPT1A in PTC was not explored. The effects of hypoxia and carnitine palmitoyl-transferase 1A (CPT1A) expression on PTC cells were determined by cell counting kit-8 assay, detection of oxidative stress, inflammation response and mitochondrial membrane motential (MMP). Oil Red O staining and the detection of free fatty acids were performed to assess the status of lipid metabolism. Flow cytometric analysis was performed to assess cell apoptosis. Quantitative polymerase chain reaction (qPCR) and western blot analysis were applied to investigate the expressions of CPT1A and HIF-1α and the molecules involved cell function. The expressions of CPT1A and HIF-1α were significantly increased in PTC cells with or without hypoxia treatment. CPT1A overexpression or silencing promoted or inhibited cell viability, and hypoxia further repressed cell viability. In addition, CPT1A overexpression alleviates hypoxia-induced increased oxidative stress, inflammation response and elevated MMP. CPT1A overexpression enhanced palmitic acid-induced decreased cell growth, enhanced the metabolic capacity of free fatty acid and suppressed cell apoptosis. Animal experiments showed that CPT1A overexpression promoted PTC tumor growth, reduced lipid deposition, oxidative stress and inflammation, as well as enhancing cell function indicators. However, CPT1A silencing showed the opposite effects both in vitro and in vivo. Hypoxia induces the high expression of HIF-1α/CPT1A, thereby reprogramming the lipid metabolism of PTC cells for adapting the hypoxia environment, meanwhile inhibiting the cell damage and apoptosis caused by oxidative stress.

A comprehensive assessment of exome capture methods for RNA sequencing of formalin-fixed and paraffin-embedded samples.

RNA-Seq analysis of Formalin-Fixed and Paraffin-Embedded (FFPE) samples has emerged as a highly effective approach and is increasingly being used in clinical research and drug development. However, the processing and storage of FFPE samples are known to cause extensive degradation of RNAs, which limits the discovery of gene expression or gene fusion-based biomarkers using RNA sequencing, particularly methods reliant on Poly(A) enrichment. Recently, researchers have developed an exome targeted RNA-Seq methodology that utilizes biotinylated oligonucleotide probes to enrich RNA transcripts of interest, which could overcome these limitations. Nevertheless, the standardization of this experimental framework, including probe designs, sample multiplexing, sequencing read length, and bioinformatic pipelines, remains an essential requirement. In this study, we conducted a comprehensive comparison of three main commercially available exome capture kits and evaluated key experimental parameters, to provide the overview of the advantages and limitations associated with the selection of library preparation protocols and sequencing platforms. The results provide valuable insights into the best practices for obtaining high-quality data from FFPE samples.

Comparison of Treatment and Prognosis Between Follicular Variant Papillary Thyroid Carcinoma and Classical Papillary Thyroid Carcinoma.

This cohort study evaluated the associations of different treatments with the prognosis of follicular variant papillary thyroid carcinoma (FVPTC) and classical papillary thyroid carcinoma (CPTC) patients. The data of 69034 PTC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year mortality of CPTC and FVPTC patients receiving surgery, radiation and combination therapy were compared. The univariable and multivariable cox proportional risk models explored the associations between different treatments and the 5-year mortality in CPTC and FVPTC patients. The 5-year mortality of CPTC patients was 2.81% and FVPTC patients was 2.47%. Compared with CPTC receiving lobectomy and/or isthmectomy, those not receiving surgery were associated with increased risk of 5-year mortality [Hazards ratio (HR)=3.27, 95% confidence interval (CI): 2.55-4.20] while total thyroidectomy was correlated with reduced risk of 5-year mortality (HR=0.67, 95%CI: 0.55-0.80). Radioactive iodine (RAI) was linked with decreased risk of 5-year mortality in CPTC patients (HR=0.57, 95%CI: 0.50-0.65). CPTC patients undergoing both surgery and radiation were related to decreased risk of 5-year mortality compared with those receiving surgery only (HR=0.55, 95%CI: 0.48-0.63). CPTC patients receiving neither surgery nor radiation (HR=4.53, 95%CI: 3.72-5.51) or those receiving radiation (HR=1.98, 95%CI: 1.13-3.48) were correlated with elevated risk of 5-year mortality. The elevated risk of 5-year mortality in FVPTC patients was reduced in those undergoing RAI (HR=0.63, 95%CI: 0.51-0.76). In conclusion, combination therapy was associated with decreased risk of 5-year mortality in CPTC and FVPTC patients, which might provide a reference for the management of these patients.

Prognostic Value of Inflammatory and Nutritional Markers for Patients With Early-Stage Poorly-to Moderately-Differentiated Cervical Squamous Cell Carcinoma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), and Onodera's prognostic nutritional index (OPNI) have been reported as prognostic markers for various cancers. We evaluated the prognostic value of the NLR, PLR, MLR, SII, SIRI, and OPNI for poorly-to moderately-differentiated cervical squamous cell carcinoma (CSCC). PATIENTS AND METHODS: We retrospectively analyzed the cases of 109 patients with early-stage poorly-to moderately-differentiated CSCC who underwent radical surgery at our institution in 2014-2017. The optimal cutoff points for the NLR, PLR, MLR, SII, SIRI, and OPNI were determined by receiver operating characteristic curves. Overall survival was analyzed by the Kaplan-Meier method. We performed a multivariate analysis using the Cox proportional hazard regression model to determine the independent prognostic indicators for early-stage poorly-to moderately-differentiated CSCC. RESULTS: The appropriate cutoff points were: NLR, 1.72; PLR, 111.96; MLR, .24; SII, 566.23; SIRI, 1.38; and OPNI, 52.68. The OS of the patients with a high OPNI (P = .04), low SII (P = .03), or low SIRI (P = .01) was significantly better. The uni- and multivariate analyses identified only the OPNI as an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC (P = .04 and P = .02). CONCLUSION: The OPNI is an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC; the NLR, PLR, MLR, SII, and SIRI are not.

Interfacial electronic properties between PtSe2 and 2D metal electrodes: a first-principles simulation.

Monolayer (ML) PtSe2 is a two-dimensional (2D) semiconductor with a modest band gap and high carrier mobility, and it is a promising 2D material for electronic devices. Finding suitable metal electrodes is a key factor in fabricating high-performance PtSe2 field effect transistors (FETs). In this study, a series of 2D metals, transition metal dichalcogenides (NbSe2, TaS2), borophene, and MXenes (V2C(OH)2, V2CF2, Nb2C(OH)2, Nb2CF2, Nb2CO2, Hf2C(OH)2, Hf2CF2) were used as electrodes for FET fabrication. The interfacial electronic properties of electrodes and PtSe2 were studied in both the vertical and lateral directions using the ab initio method. In the vertical direction, PtSe2 formed ohmic contacts with most of the 2D metals except for Nb2CF2 and Hf2CF2. Specifically, in the cases of Nb2CF2 and Hf2CF2, p- and n-type Schottky contacts were formed with Schottky barrier heights (SBHs) of 0.48 eV and 0.02 eV, respectively. In the lateral direction, PtSe2 with contacting Hf2CF2 and V2C(OH)2 electrodes formed n-type Schottky contacts with SBHs of 0.14 eV and 0.09 eV, respectively. In the cases of TaS2 and Nb2CF2 electrodes, p-type Schottky contacts with SBHs of 0.35 eV and 0.29 eV, respectively, were formed. Moreover, n-type ohmic contacts were observed when Hf2C(OH)2 and Nb2C(OH)2 electrodes were applied, and p-type ohmic contacts were formed when borophene, NbSe2, Nb2CO2, and V2CF2 electrodes were used. This work reports a systematic investigation of ML PtSe2-2D metal interfaces and serves as a practical guide for selecting electrode materials for PtSe2 FETs.

Regulating the electronic properties of the WGe2N4 monolayer by adsorption of 4d transition metal atoms towards spintronic devices.

We study the regulation of the electronic and spin transport properties of the WGe2N4 monolayer by adsorbing 4d transition metal atoms (Y-Cd) using density functional theory combined with non-equilibrium Green's function. It is found that the adsorption of transition metal atoms (except Pd, Ag and Cd atoms) can introduce a magnetic moment into the WGe2N4 monolayer. Among the transition metal atoms, the adsorption of Nb and Rh atoms transforms WGe2N4 from a semiconductor to a half-metal and a highly spin-polarized semiconductor, respectively. The half-metallic Nb-adsorbed WGe2N4 system is selected to investigate the spin transport properties, and a high magnetoresistance ratio of 107% is achieved. In both parallel and antiparallel magnetization configurations, the spin filtering efficiency reaches close to 100% in the whole bias range, and the antiparallel magnetization configuration exhibits a dual spin filtering effect with a rectification ratio of up to 104. Our study predicts that the adsorption of 4d transition metal heteroatoms is an effective method to regulate the electronic and magnetic properties of WGe2N4 towards high-performance spintronic devices.

The crosstalk between NLRP3 inflammasome and gut microbiome in atherosclerosis.

Atherosclerosis (AS) is chronic pathological process based on the inflammatory reaction associated with factors including vascular endothelial dysfunction, inflammation, and autoimmunity. Inflammasomes are known to be at the core of the inflammatory response. As a pattern recognition receptor of innate immunity, the NLRP3 inflammasome mediates the secretion of inflammatory factors by activating the Caspase-1, which is important for maintaining the immune system and regulating the gut microbiome, and participates in the occurrence and development of AS. The intestinal microecology is composed of a large number of complex structures of gut microbiota and its metabolites, which play an important role in AS. The gut microbiota and its metabolites regulate the activation of the NLRP3 inflammasome. Targeting the NLRP3 inflammasome and regulating intestinal microecology represent a new direction for the treatment of AS. This paper systematically reviews the interaction between the NLRP3 inflammasome and gut microbiome in AS, strategies for targeting the NLRP3 inflammasome and gut microbiome for the treatment of AS, and provides new ideas for the research and development of drugs for the treatment of AS.

Design of multifunctional spin logic gates based on manganese porphyrin molecules connected to graphene electrodes.

The spin-resolved transport properties of molecular logic devices composed of two Mn porphyrin molecules connected to each other via a six-carbon atomic chain were studied using the non-equilibrium Green's function combined with density functional theory. The molecules were symmetrically connected to armchair graphene nanoribbon electrodes through four-carbon atomic chains on the left- and right-hand sides. Our calculations revealed that the spin-resolved current-voltage curves depend on the initial spin setting of the transition metal Mn atoms and carbon atoms on the zigzag edges where the electrodes come in contact with the molecule. By simultaneously regulating the spin orientations of the intermediate functional molecules and the zigzag edges of the armchair graphene nanoribbon electrodes, seven spin polarization configurations were obtained. These configurations were examined in this study considering the spin-related symmetry of molecular junctions. By meticulously selecting different combinations according to the specific input and output signals, YES, NOT, OR, NOR, and XOR multifarious spin logic devices were created. The findings of this study are expected to contribute toward the extension of molecular junction functions in future spintronic integrated circuit design and further miniaturization.

Schottky diodes based on blue phosphorene nanoribbon homojunctions.

Diodes have been widely studied as one of the most commonly used electronic components in circuits, and it is important to find diodes with an excellent rectification performance. Herein, we investigate the electronic and transport properties of Schottky contact diodes based on zigzag hydrogenated blue phosphorene nanoribbons, by employing density functional theory combined with the non-equilibrium Green's function. It is found that the adsorption of transition metal atoms Sc/Cr/Ti and Ni on the top site of blue phosphorene nanoribbons leads to metallic and semiconducting properties, respectively. Devices consisting of the planar contact of the metallic and semiconducting nanoribbons show rectifying behavior due to the Schottky barriers of the homojunctions. The current is preferential to flow from the semiconducting side to the metallic side. The rectification ratio of the Sc-Ni device and the Cr-Ni device can reach up to 108, which is much higher than that of traditional p-n junctions of about 105-107. The high rectification ratio at low bias regions, together with the low threshold voltages and negligible reverse currents, make blue phosphorene nanoribbon homojunctions ideal rectifier diodes.

Based on proteomics to explore the mechanism of mecobalamin promoting the repair of injured peripheral nerves.

Mecobalamin is commonly used in the adjuvant intervention of various peripheral nerve injuries. Actin cytoskeleton plays a role in the regeneration of myelin and axon. Therefore, the purpose of this study was to explore the possibility of mecobalamin regulating actin cytoskeleton in repairing nerve injury. In this study, a crush injury on the right sciatic nerve of two groups of rats (12 in each group) was established. The control group was only given normal saline (i.g.), and the intervention group was given mecobalamin 1 mg/kg (i.g.). The rats were sacrificed on 28th day and the injured nerves were collected for proteomics. The result shows that regulation of actin cytoskeleton pathway changed significantly. The expression of protein Vav1 was verified by Western blot and immunofluorescence. In the intervention group, the nerve fiber structure was complete, the axons were dense and symmetrical, and the myelin sheath was compact and uniform in thickness. The positive rate of myelin basic protein and ßⅢ-tubulin was higher than that in the control group. The findings of the study show that mecobalamin regulates the actin cytoskeleton in the repair of nerve damage and upregulates Vav1 in the regulation of actin cytoskeleton pathway.

Prognostic Value and Oncogenic Effects of Ubiquitin-Specific Protease 43 in Lung Squamous Cell Carcinoma.

Dysregulated expression of ubiquitin-specific protease 43 (USP43) has been recently discovered in malignancies. This study aimed to investigate the expression pattern of USP43 protein in lung squamous cell carcinoma (LUSC) and to explore its correlation with patients' clinicopathological characteristics as well as clinical outcomes. Expression of USP43 protein was determined by immunohistochemistry staining in a retrospective cohort containing 157 LUSC cases who underwent curative surgery in our hospital. Accordingly, USP43 protein was positively correlated with tumor size, depth of invasion, and lymph node metastasis. Patients with increased USP43 expression or positive lymph nodes exhibited a poorer overall survival. In addition, cellular assays elucidated that USP43 can promote LUSC growth and invasion. Taken together, our study demonstrated that USP43 may act as a proto-oncogene, which could be a promising biomarker and therapeutic target in the survival prediction and treatment of LUSC.

Incidence and prognosis of thyroid cancer in children: based on the SEER database.

OBJECTIVE: To update the recognition of the trends in the incidence of childhood thyroid cancer (TC) and its prognosis. METHODS: A large-scale sample based on long time-line public database was recruited. Join-point regression model was used to analyze the incidence trend of childhood TC. Univariable and multivariable Cox regression model analyses were applied to explore the survival situation and prognostic factors. RESULTS: The incidence rate of childhood TC increased between 1975 and 2016 from 3.8/million (95% CI 2.6-5.5) to 11.5/million (95% CI 9.2-14.1), AAPC = 2.38% (95% CI 1.98-9.65) and could be divided into two stages of increasing trends. The incidence rate of Trend1 (1975-2005) increased slowly (APC = 1.08%, 95% CI 0.38-1.82) while Trend2 (2005-2016) increased dramatically (APC = 6.77%, 95% CI 4.30-9.28). Annual incidence rate of small size tumor (< 4 cm) and local stage childhood TC increased significantly. The overall cumulative survival rate for childhood TC was high up to 97-99%. Males, black race, MTC type, distant metastasis, tumor size ≥ 4 cm, non-primary cancer were the independent risk factors of childhood TC prognosis. CONCLUSION: A contribution of overdetection to rising pediatric TC rates might not be able to rule out. For clinical implications, screening TC in children with potential specific risk factors is feasible. Over-treatment to small size and local stage TC in children should be avoided.

[Effects of astragaloside â £ on inflammatory response and percentage of peripheral blood Th17 cells in mice with ulcerative colitis].

This study aimed to investigate the anti-inflammatory effect of astragaloside Ⅳ in mice with ulcerative colitis(UC) and its effect on the percentage of peripheral blood T helper(Th17) cells. Following the establishment of UC mouse model with 2% sodium dextran sulfate(DSS), mice in the positive control group and low-and high-dose astragaloside Ⅳ groups were treated with corresponding drugs by gavage. Disease activity index(DAI) was calculated, and serum interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), and transforming growth factor-ß(TGF-ß) levels were assayed by ELISA. The pathological changes in colon tissue were observed by HE staining, and Th17/regulatory T cells(Treg) ratio in the peripheral blood was determined by flow cytometry. Western blot was conducted for detecting the relative protein expression levels of forkhead box protein P3(Foxp3) and retinoic acid-related orphan nuclear receptor γT(ROR-γt). The findings demonstrated that in normal mice, the colonic structure was intact. The goblet cells were not reduced and the glands were neatly arranged, with no mucosal erosion, bleeding, or positive cell infiltration. In the model group, the colonic mucosal structure was seriously damaged, manifested as disordered arrangement or missing of glands, vascular dilatation, congestion, and massive inflammatory cell infiltration. The pathological injury of colon tissue was alleviated to varying degrees in drug treatment groups. Compared with the normal group, the model group exhibited elevated percentage of Th17 cells, increased IL-17 and TNF-α content, up-regulated relative ROR-γt protein expression, lowered TGF-ß, reduced percentage of Treg cells, and down-regulated relative Foxp3 protein expression. The comparison with the model group showed that DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the positive control group, low-dose astragaloside Ⅳ group, and high-dose astragaloside Ⅳ group were decreased, while TGF-ß content, percentage of Treg cells, and relative Foxp3 protein expression were increased. The DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the low-dose astragaloside Ⅳ group were higher than those in the positive control group, whereas the content of TGF-ß, percentage of Treg cells, and relative Foxp3 protein expression were lower. DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, relative ROR-γt protein expression in the high-dose astragaloside Ⅳ group declined in contrast to those in the low-dose astragaloside Ⅳ group, while the TGF-ß content, percentage of Treg cells, and relative Foxp3 protein expression rose. There was no significant difference between the positive control group and the high-dose astragaloside Ⅳ group. Astragaloside Ⅳ is able to inhibit inflammatory response and diminish the percentage of Th17 cells in mice with UC.

H19/miR-107/HMGB1 axis sensitizes laryngeal squamous cell carcinoma to cisplatin by suppressing autophagy in vitro and in vivo.

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor, which occurs in the head and neck. Current treatments for LSCC are all largely weakened by increasing drug resistance. Our study aimed to investigate the effects of long noncoding RNA (lncRNA) H19 on drug resistance in LSCC. In our study, we found that the level of H19 was sharply upregulated in LSCC tissues and drug-resistant cells compared with the control. Besides, the expression of high-mobility group B1 (HMGB1) was elevated, and microRNA107 (miR-107) was suppressed in drug-resistant cells compared with the control. Further study revealed that the interference of H19 by short hairpin RNA (shRNA) effectively suppressed high autophagy level and obvious drug resistance in drug-resistant cells. Besides that, miR-107 was predicted as a target of H19 and inhibiting effects of H19 shRNA on autophagy and drug resistance were both reversed by miR-107 inhibitor. Moreover, HMGB1 was predicted as a target of miR-107 in LSCC cells and knockdown of HMGB1 was able to suppress autophagy and drug resistance in LSCC cells. In addition, our investigation demonstrated that H19 shRNA exerted an inhibiting effect on autophagy and drug resistance by downregulating HMGB1 by targeting miR-107. Finally, the in vivo experiment revealed that LV-H19 shRNA strongly suppressed drug resistance compared with the usage of cisplatin individually. Taken together, our research indicated an H19-miR-107-HMGB1 axis in regulating the autophagy-induced drug resistance in LSCC in vitro and in vivo, providing novel targets for molecular-targeted therapy and broadening the research for LSCC.

A Fluorogenic and Chromogenic Probe Distinguishes Fluoride Anions and Thiols: Implications for Discrimination of Fluoride-Containing G Series and Sulfur-Containing V Series Nerve Agents.

A coumarin-based probe, FP2, was designed for the differential detection of fluoride anions and thiols, i.e., the corresponding nucleophilic substitution products from fluorine-containing G agents and sulfur-containing V agents, thus having the potential to discriminate between these two nerve agents. FP2 with two functional reaction groups, α, ß-unsaturated ketone and silyl groups, can react selectively with fluoride anions and thiols at the µM level respectively. Intriguingly, in the THF solution, FP2 reacts with the fluoride anion but not with the thiol, whereas in the EtOH/HEPES solution, FP2 reacts with the thiol but not with the fluoride anion. As a result, FP2 can produce different fluorophores in the two detection solutions, thus displaying significant fluorescence changes. In addition, the FP2 detection system can show a significant color change from colorless to yellow within seconds when detecting fluoride anions in THF detection solutions, and from yellow to light blue when detecting thiols in EtOH/HEPES solutions, which will facilitate visual detection by emergency responders at the scene of an incident involving a nerve agent.

Prognostic value of Onodera's nutritional index for intermediate- and high-risk gastrointestinal stromal tumors treated with or without tyrosine kinase inhibitors.

BACKGROUND: Immunoinflammatory and nutritional markers, such as the peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and Onodera's prognostic nutritional index (OPNI), have gained considerable attention and have been preliminarily revealed as prognostic markers of gastrointestinal stromal tumors (GISTs). METHODS: In this study, we first investigated the prognostic value of OPNI in GISTs treated with or without TKIs based on the propensity score matching (PSM) method. All of the patients had received surgical resection for primary GIST, and data from 2010 to 2018 were initially and retrospectively identified from our gastrointestinal center. Recurrence-free survival (RFS) was calculated by the Kaplan-Meier method and compared by the log-rank test. RESULTS: The patients were divided into groups treated and not treated with TKIs, and we used the propensity score matching method to homogenize their baseline data. Multivariate Cox proportional hazard regression models were applied to identify associations with outcome variables. A total of 563 GISTs were initially chosen, and 280 of them were included for analysis under the inclusion criteria. After PSM, there were 200 patients included. Multivariate analyses identified OPNI as an independent prognostic marker that was associated with primary site, tumor size, mitotic index, tumor rupture, necrosis, and modified NIH risk classification. Low OPNI (< 42.6; HR 0.409; P < 0.001) was associated with worse RFS. CONCLUSIONS: Preoperative OPNI is a novel and useful prognostic marker for GISTs both treated and not treated with TKIs. Higher NLR and PLR have negative effects on RFS.